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Sample records for hiv-1 serodiscordant couples

  1. Sexual and Reproductive Health in HIV Serodiscordant Couples

    African Journals Online (AJOL)

    AJRH Managing Editor

    Keywords: HIV, Serodiscordant couple, Conception, Contraception, infertility. Résumé. Les couples ... risk of sexual transmission of HIV from male-to- female as 0.1-0.3% per ... Antiretroviral Drugs in Serodiscordant Couples. The use of ARV ...

  2. Characteristics of HIV-1 serodiscordant couples enrolled in a clinical trial of antiretroviral pre-exposure prophylaxis for HIV-1 prevention.

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    Andrew Mujugira

    Full Text Available Stable heterosexual HIV-1 serodiscordant couples in Africa have high HIV-1 transmission rates and are a critical population for evaluation of new HIV-1 prevention strategies. The Partners PrEP Study is a randomized, double-blind, placebo-controlled trial of tenofovir and emtricitabine-tenofovir pre-exposure prophylaxis to decrease HIV-1 acquisition within heterosexual HIV-1 serodiscordant couples. We describe the trial design and characteristics of the study cohort.HIV-1 serodiscordant couples, in which the HIV-1 infected partner did not meet national guidelines for initiation of antiretroviral therapy, were enrolled at 9 research sites in Kenya and Uganda. The HIV-1 susceptible partner was randomized to daily oral tenofovir, emtricitabine-tenofovir, or matching placebo with monthly follow-up for 24-36 months.From July 2008 to November 2010, 7920 HIV-1 serodiscordant couples were screened and 4758 enrolled. For 62% (2966/4758 of enrolled couples, the HIV-1 susceptible partner was male. Median age was 33 years for HIV-1 susceptible and HIV-1 infected partners [IQR (28-40 and (26-39 respectively]. Most couples (98% were married, with a median duration of partnership of 7.0 years (IQR 3.0-14.0 and recent knowledge of their serodiscordant status [median 0.4 years (IQR 0.1-2.0]. During the month prior to enrollment, couples reported a median of 4 sex acts (IQR 2-8; 27% reported unprotected sex and 14% of male and 1% of female HIV-1 susceptible partners reported sex with outside partners. Among HIV-1 infected partners, the median plasma HIV-1 level was 3.94 log(10 copies/mL (IQR 3.31-4.53 and median CD4 count was 496 cells/µL (IQR 375-662; the majority (64% had WHO stage 1 HIV-1 disease.Couples at high risk of HIV-1 transmission were rapidly recruited into the Partners PrEP Study, the largest efficacy trial of oral PrEP. (ClinicalTrials.gov NCT00557245.

  3. Stakeholders perception of HIV sero-discordant couples in western Kenya.

    Science.gov (United States)

    Were, E; Wools-Kaloustian, K; Baliddawa, J; Ayuo, P O; Sidle, J; Fife, K

    2008-07-01

    To describe the perceptions of key stakeholders regarding the counselling needs of HIV sero-discordant couples as part of preparation for a clinical trial involving HIV sero-discordant couples. Qualitative study using key informant and couple interviews. Moi Teaching and Referral Hospital (MTRH). A purposive sample of nine key informants and 31 couple interviews totaling 71 participants. The couple interviews consisted of HIV untested, HIV concordant (positive and negative) and discordant couples. Seventy one individuals participated in nine key informant and 31 couple interviews. The responses identified the following as key issues in counselling HIV discordant couples: The need for education on the meaning of HIV sero-discordancy including potential sources of infection; assistance in disclosing HIV test results to one's partner; discussion of the stigma surrounding formula feeding. Overall, the participants supported safer sexual practices in discordant partnerships. Psychosocial support of HIV sero-discordant couples should include messages about the meaning, mechanisms and implications of sero-discordancy. Culturally appropriate HIV-disclosure and safer sex messages are also needed to support these partnerships.

  4. HIV sero-discordance among Nigerian couples: challenges and ...

    African Journals Online (AJOL)

    History of extramarital affairs, alcoholism, viral subtype, age range and duration of marriage were seen as independent behavioral and sexual risk factors for HIV infection among spouses that were HIV-infected in sero-discordant relationship. The highest incidence of HIV sero-discordance occurred among couples < 5 years ...

  5. Brief Report: Medication Sharing Is Rare Among African HIV-1 Serodiscordant Couples Enrolled in an Efficacy Trial of Oral Pre-exposure Prophylaxis (PrEP) for HIV-1 Prevention.

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    Thomson, Kerry A; Haberer, Jessica E; Marzinke, Mark A; Mujugira, Andrew; Hendrix, Craig W; Celum, Connie; Ndase, Patrick; Ronald, Allan; Bangsberg, David R; Baeten, Jared M

    2017-06-01

    Sharing of pre-exposure prophylaxis (PrEP) medications is a concern for PrEP implementation. For HIV-1 serodiscordant couples, sharing may undermine the HIV-1 prevention benefit and also cause antiretroviral resistance if taken by HIV-1 infected partners. Within a PrEP efficacy trial among HIV-1 serodiscordant couples, we assessed the occurrence of PrEP sharing by self-report and plasma tenofovir concentrations in HIV-1 infected partners. PrEP sharing was self-reported at <0.01% of visits, and 0%-1.6% of randomly selected and 0% of purposively selected specimens from HIV-1 infected participants had detectable tenofovir concentrations (median: 66.5 ng/mL, range: 1.3-292 ng/mL). PrEP sharing within HIV-1 serodiscordant couples was extremely rare.

  6. Stakeholders perception of HIV sero-discordant couples in western ...

    African Journals Online (AJOL)

    Stakeholders perception of HIV sero-discordant couples in western Kenya. E Were, K Wools-Kaloustian, J Baliddawa, PO Ayuo, J Sidle, K Fife. Abstract. Objective: To describe the perceptions of key stakeholders regarding the counselling needs of HI V sero-discordant couples as part of preparation for a clinical trial ...

  7. Achieving pregnancy safely for HIV-serodiscordant couples: a social ecological approach.

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    Saleem, Haneefa T; Narasimhan, Manjulaa; Denison, Julie A; Kennedy, Caitlin E

    2017-03-08

    The recognition and fulfilment of the sexual and reproductive health and rights (SRHR) of all individuals and couples affected by HIV, including HIV-serodiscordant couples, requires intervention strategies aimed at achieving safe and healthy pregnancies and preventing undesired pregnancies. Reducing risk of horizontal and vertical transmission and addressing HIV-related infertility are key components of such interventions. In this commentary, we present challenges and opportunities for achieving safe pregnancies for serodiscordant couples through a social ecological lens. At the individual level, knowledge (e.g. of HIV status, assisted reproductive technologies) and skills (e.g. adhering to antiretroviral therapy or pre-exposure prophylaxis) are important. At the couple level, communication between partners around HIV status disclosure, fertility desires and safer pregnancy is required. Within the structural domain, social norms, stigma and discrimination from families, community and social networks influence individual and couple experiences. The availability and quality of safer conception and fertility support services within the healthcare system remains essential, including training for healthcare providers and strengthening integration of SRHR and HIV services. Policies, legislation and funding can improve access to SRHR services. A social ecological framework allows us to examine interactions between levels and how interventions at multiple levels can better support HIV-serodiscordant couples to achieve safe pregnancies. Strategies to achieve safer pregnancies should consider interrelated challenges at different levels of a social ecological framework. Interventions across multiple levels, implemented concurrently, have the potential to maximize impact and ensure the full SRHR of HIV-serodiscordant couples.

  8. A flexible method to model HIV serodiscordance among couples in Mozambique.

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    Adelino J C Juga

    Full Text Available Whereas the number of people newly infected by HIV is continuing to decline globally, the epidemic continues to expand in many parts of the world. As the HIV/AIDS epidemic has matured in many countries, it is believed that the proportion of new infections occurring within couples has risen. Across countries, including Mozambique, a sizeable proportion of couples with HIV infection are discordant. A serodiscordant couple is a couple in which one partner has tested positive for HIV and the other has not. To describe the HIV serodiscordance among couples, a variety of association measures can be used. In this paper, we propose the serodiscordance measure (SDM as a new alternative measure. Focus is on the specification of flexible marginal and random effects models for multivariate correlated binary data together with a full-likelihood estimation method, to adequately and directly describe the measure of interest. Fitting joint models allows examining the effects of different risk factors and other covariates on the probability to be HIV positive for each member within a couple, and estimating common effects for both probabilities more efficiently, while accounting for the association between their infection status. Moreover, the interpretation of the proposed association parameter SDM is more direct and relevant and effects of covariates can be studied as well. Results show that the HIV prevalence for the province where a couple was located as well as the union number for the woman within a couple are factors associated with HIV serodiscordance. These findings are important for the Mozambican public health policy makers to design national prevention plans, which include policies to stimulate regular HIV testing for couples as well as adolescents and young adults, prior to getting married or living together as a couple.

  9. Increased Risk of HIV-1 Transmission in Pregnancy: A Prospective Study among African HIV-1 Serodiscordant Couples

    Science.gov (United States)

    MUGO, Nelly R.; HEFFRON, Renee; DONNELL, Deborah; WALD, Anna; WERE, Edwin O.; REES, Helen; CELUM, Connie; KIARIE, James N.; COHEN, Craig R.; KAYINTEKORE, Kayitesi; BAETEN, Jared M.

    2011-01-01

    Background Physiologic and behavioral changes during pregnancy may alter HIV-1 susceptibility and infectiousness. Prospective studies exploring pregnancy and HIV-1 acquisition risk in women have found inconsistent results. No study has explored the effect of pregnancy on HIV-1 transmission risk from HIV-1 infected women to male partners. Methods In a prospective study of African HIV-1 serodiscordant couples, we evaluated the relationship between pregnancy and the risk of 1) HIV-1 acquisition among women and 2) HIV-1 transmission from women to men. Results 3321 HIV-1 serodiscordant couples were enrolled, 1085 (32.7%) with HIV-1 susceptible female partners and 2236 (67.3%) with susceptible male partners. HIV-1 incidence in women was 7.35 versus 3.01 per 100 person-years during pregnant and non-pregnant periods (hazard ratio [HR] 2.34, 95% confidence interval [CI] 1.33–4.09). This effect was attenuated and not statistically significant after adjusting for sexual behavior and other confounding factors (adjusted HR 1.71, 95% CI 0.93–3.12). HIV-1 incidence in male partners of infected women was 3.46 versus 1.58 per 100 person-years when their partners were pregnant versus not pregnant (HR 2.31, 95% CI 1.22–4.39). This effect was not attenuated in adjusted analysis (adjusted HR 2.47, 95% CI 1.26–4.85). Conclusions HIV-1 risk increased two-fold during pregnancy. Elevated risk of HIV-1 acquisition in pregnant women appeared in part to be explained by behavioral and other factors. This is the first study to show pregnancy increased the risk of female-to-male HIV-1 transmission, which may reflect biological changes of pregnancy that could increase HIV-1 infectiousness. PMID:21785321

  10. Strategies to prevent HIV transmission to serodiscordant couples.

    Science.gov (United States)

    Hallal, Ronaldo Campos; Raxach, Juan Carlos; Barcellos, Nêmora Tregnago; Maksud, Ivia

    2015-09-01

    The use antiretroviral reduces the sexual transmission of HIV, expanding interventions for serodiscordant couples. This article aims to review the use of antiretroviral and other prevention interventions among serodiscordant couples and to analyze its use in Brazil. A retrospective review was performed through the MEDLINE database and bases included in the Biblioteca Virtual em Saúde. The articles recovered exhibit four main strategies: (1) condom; (2) reduction of risks in sexual practices; (3) use of antiretrovirals, particularly early initiation of antiretroviral therapy (TASP) and pre-exposure prophylaxis (PrEP); (4) risk reduction in reproduction. TASP is highly effective in reducing sexual transmission, PrEP was tested in serodiscordant couples and both reduce the sexual transmission risk in different sexual practices, enabling individualized prevention strategies. When used in combination, antiretrovirals and sexual practices with condoms offer greater efficacy than any single strategy. The combined use of new and old strategies allows us to build a prevention policy for all.

  11. Strategies to prevent HIV transmission to serodiscordant couples

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    Ronaldo Campos Hallal

    2015-09-01

    Full Text Available ABSTRACTIntroduction:The use antiretroviral reduces the sexual transmission of HIV, expanding interventions for serodiscordant couples.Objective:This article aims to review the use of antiretroviral and other prevention interventions among serodiscordant couples and to analyze its use in Brazil.Methods:A retrospective review was performed through the MEDLINE database and bases included in the Biblioteca Virtual em Saúde.Results:The articles recovered exhibit four main strategies: (1 condom; (2 reduction of risks in sexual practices; (3 use of antiretrovirals, particularly early initiation of antiretroviral therapy (TASP and pre-exposure prophylaxis (PrEP; (4 risk reduction in reproduction.Discussion:TASP is highly effective in reducing sexual transmission, PrEP was tested in serodiscordant couples and both reduce the sexual transmission risk in different sexual practices, enabling individualized prevention strategies.Conclusions:When used in combination, antiretrovirals and sexual practices with condoms offer greater efficacy than any single strategy. The combined use of new and old strategies allows us to build a prevention policy for all.

  12. Evaluating Safer Conception Options for HIV-Serodiscordant Couples (HIV-Infected Female/HIV-Uninfected Male: A Closer Look at Vaginal Insemination

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    Okeoma Mmeje

    2012-01-01

    Full Text Available HIV serodiscordant couples represent at least half of all HIV-affected couples worldwide. Many of these couples have childbearing desires. Safer methods of conception may allow for pregnancy while minimizing the risk of sexual transmission of HIV. In serodiscordant partnerships with an HIV-infected female and HIV-uninfected male, vaginal insemination of a partner's semen during the fertile period coupled with 100% condom use may be the safest method of conception.

  13. Optimal uses of antiretrovirals for prevention in HIV-1 serodiscordant heterosexual couples in South Africa: a modelling study.

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    Timothy B Hallett

    2011-11-01

    Full Text Available Antiretrovirals have substantial promise for HIV-1 prevention, either as antiretroviral treatment (ART for HIV-1-infected persons to reduce infectiousness, or as pre-exposure prophylaxis (PrEP for HIV-1-uninfected persons to reduce the possibility of infection with HIV-1. HIV-1 serodiscordant couples in long-term partnerships (one member is infected and the other is uninfected are a priority for prevention interventions. Earlier ART and PrEP might both reduce HIV-1 transmission in this group, but the merits and synergies of these different approaches have not been analyzed.We constructed a mathematical model to examine the impact and cost-effectiveness of different strategies, including earlier initiation of ART and/or PrEP, for HIV-1 prevention for serodiscordant couples. Although the cost of PrEP is high, the cost per infection averted is significantly offset by future savings in lifelong treatment, especially among couples with multiple partners, low condom use, and a high risk of transmission. In some situations, highly effective PrEP could be cost-saving overall. To keep couples alive and without a new infection, providing PrEP to the uninfected partner could be at least as cost-effective as initiating ART earlier in the infected partner, if the annual cost of PrEP is 70% effective.Strategic use of PrEP and ART could substantially and cost-effectively reduce HIV-1 transmission in HIV-1 serodiscordant couples. New and forthcoming data on the efficacy of PrEP, the cost of delivery of ART and PrEP, and couples behaviours and preferences will be critical for optimizing the use of antiretrovirals for HIV-1 prevention. Please see later in the article for the Editors' Summary.

  14. Sociodemographic, behavioral, and clinical correlates of inconsistent condom use in HIV-serodiscordant heterosexual couples.

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    Buchacz, K; van der Straten, A; Saul, J; Shiboski, S C; Gomez, C A; Padian, N

    2001-11-01

    We examined sociodemographic, behavioral, and clinical characteristics associated with inconsistent condom use in a cross-sectional analysis of 145 sexually active HIV-serodiscordant heterosexual couples who participated in the California Partners Study II. All couples were aware of their HIV-serodiscordant status. Forty-five percent of couples reported having had unprotected vaginal or anal sex in the previous 6 months. In the multivariate couple-level analyses, factors independently associated with inconsistent (i.e., <100%) condom use in the previous 6 months included lower educational level, unemployment, African-American ethnicity, and practice of anal sex by the couple. Injection drug use was associated with inconsistent condom use among couples with younger HIV-infected partners. In addition, couples with HIV-infected partners who had higher CD4 cell counts and couples in which the HIV-infected male partner ever had sex with a man were more likely to use condoms inconsistently. Consistency of condom use did not depend on the gender of the HIV-infected partner or duration of sexual relationship. The findings suggest that many HIV-serodiscordant heterosexual couples remain at high risk of HIV transmission and may benefit not only from behavioral interventions but also from structural interventions aimed at improving their social and economic conditions.

  15. Counseling Framework for HIV-Serodiscordant Couples on the Integrated Use of Antiretroviral Therapy and Pre-exposure Prophylaxis for HIV Prevention.

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    Morton, Jennifer F; Celum, Connie; Njoroge, John; Nakyanzi, Agnes; Wakhungu, Imeldah; Tindimwebwa, Edna; Ongachi, Snaidah; Sedah, Eric; Okwero, Emmanuel; Ngure, Kenneth; Odoyo, Josephine; Bulya, Nulu; Haberer, Jessica E; Baeten, Jared M; Heffron, Renee

    2017-01-01

    For HIV-serodiscordant couples, integrated delivery of antiretroviral therapy (ART) for HIV-positive partners and time-limited pre-exposure prophylaxis (PrEP) for negative partners virtually eliminates HIV transmission. Standardized messaging, sensitive to the barriers and motivators to HIV treatment and prevention, is needed for widespread scale-up of this approach. Within the Partners Demonstration Project, a prospective interventional project among 1013 serodiscordant couples in Kenya and Uganda, we offered ART to eligible HIV-positive partners and PrEP to HIV-negative partners before ART initiation and through the HIV-positive partner's first 6 months of ART use. We conducted individual and group discussions with counseling staff to elicit the health communication framework and key messages about ART and PrEP that were delivered to couples. Counseling sessions for serodiscordant couples about PrEP and ART included discussions of HIV serodiscordance, PrEP and ART initiation and integrated use, and PrEP discontinuation. ART messages emphasized daily, lifelong use for treatment and prevention, adherence, viral suppression, resistance, side effects, and safety of ART during pregnancy. PrEP messages emphasized daily dosing, time-limited PrEP use until the HIV-positive partner sustained 6 months of high adherence to ART, adherence, safety during conception, side effects, and other risks for HIV. Counseling messages for HIV-serodiscordant couples are integral to the delivery of time-limited PrEP as a "bridge" to ART-driven viral suppression. Their incorporation into programmatic scale-up will maximize intervention impact on the global epidemic.

  16. A Scoring Tool to Identify East African HIV-1 Serodiscordant Partnerships with a High Likelihood of Pregnancy.

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    Heffron, Renee; Cohen, Craig R; Ngure, Kenneth; Bukusi, Elizabeth; Were, Edwin; Kiarie, James; Mugo, Nelly; Celum, Connie; Baeten, Jared M

    2015-01-01

    HIV-1 prevention programs targeting HIV-1 serodiscordant couples need to identify couples that are likely to become pregnant to facilitate discussions about methods to minimize HIV-1 risk during pregnancy attempts (i.e. safer conception) or effective contraception when pregnancy is unintended. A clinical prediction tool could be used to identify HIV-1 serodiscordant couples with a high likelihood of pregnancy within one year. Using standardized clinical prediction methods, we developed and validated a tool to identify heterosexual East African HIV-1 serodiscordant couples with an increased likelihood of becoming pregnant in the next year. Datasets were from three prospectively followed cohorts, including nearly 7,000 couples from Kenya and Uganda participating in HIV-1 prevention trials and delivery projects. The final score encompassed the age of the woman, woman's number of children living, partnership duration, having had condomless sex in the past month, and non-use of an effective contraceptive. The area under the curve (AUC) for the probability of the score to correctly predict pregnancy was 0.74 (95% CI 0.72-0.76). Scores ≥ 7 predicted a pregnancy incidence of >17% per year and captured 78% of the pregnancies. Internal and external validation confirmed the predictive ability of the score. A pregnancy likelihood score encompassing basic demographic, clinical and behavioral factors defined African HIV-1 serodiscordant couples with high one-year pregnancy incidence rates. This tool could be used to engage African HIV-1 serodiscordant couples in counseling discussions about fertility intentions in order to offer services for safer conception or contraception that align with their reproductive goals.

  17. A Scoring Tool to Identify East African HIV-1 Serodiscordant Partnerships with a High Likelihood of Pregnancy.

    Directory of Open Access Journals (Sweden)

    Renee Heffron

    Full Text Available HIV-1 prevention programs targeting HIV-1 serodiscordant couples need to identify couples that are likely to become pregnant to facilitate discussions about methods to minimize HIV-1 risk during pregnancy attempts (i.e. safer conception or effective contraception when pregnancy is unintended. A clinical prediction tool could be used to identify HIV-1 serodiscordant couples with a high likelihood of pregnancy within one year.Using standardized clinical prediction methods, we developed and validated a tool to identify heterosexual East African HIV-1 serodiscordant couples with an increased likelihood of becoming pregnant in the next year. Datasets were from three prospectively followed cohorts, including nearly 7,000 couples from Kenya and Uganda participating in HIV-1 prevention trials and delivery projects.The final score encompassed the age of the woman, woman's number of children living, partnership duration, having had condomless sex in the past month, and non-use of an effective contraceptive. The area under the curve (AUC for the probability of the score to correctly predict pregnancy was 0.74 (95% CI 0.72-0.76. Scores ≥ 7 predicted a pregnancy incidence of >17% per year and captured 78% of the pregnancies. Internal and external validation confirmed the predictive ability of the score.A pregnancy likelihood score encompassing basic demographic, clinical and behavioral factors defined African HIV-1 serodiscordant couples with high one-year pregnancy incidence rates. This tool could be used to engage African HIV-1 serodiscordant couples in counseling discussions about fertility intentions in order to offer services for safer conception or contraception that align with their reproductive goals.

  18. Knowledge of HIV serodiscordance, transmission, and prevention among couples in Durban, South Africa.

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    William Kilembe

    Full Text Available Couples' voluntary HIV counseling and testing (CVCT significantly decreases HIV transmission within couples, the largest risk group in sub-Saharan Africa, but it is not currently offered in most HIV testing facilities. To roll out such an intervention, understanding locale-specific knowledge barriers is critical. In this study, we measured knowledge of HIV serodiscordance, transmission, and prevention before and after receipt of CVCT services in Durban.Pre- and post-CVCT knowledge surveys were administered to a selection of individuals seeking CVCT services.Changes in knowledge scores were assessed with McNemar Chi-square tests for balanced data and generalized estimating equation methods for unbalanced data.The survey included 317 heterosexual black couples (634 individuals who were primarily Zulu (87%, unemployed (47%, and had at least a secondary level education (78%. 28% of couples proved to be discordant. Only 30% of individuals thought serodiscordance between couples was possible pre-CVCT compared to 95% post-CVCT. One-third thought there was at least one benefit of CVCT pre-CVCT, increasing to 96% post-CVCT. Overall, there were positive changes in knowledge about HIV transmission and prevention. However, many respondents thought all HIV positive mothers give birth to babies with AIDS (64% pre-CVCT, 59% post-CVCT and that male circumcision does not protect negative men against HIV (70% pre-CVCT, 67% post-CVCT.CVCT was well received and was followed by improvements in understanding of discordance, the benefits of joint testing, and HIV transmission. Country-level health messaging would benefit from targeting gaps in knowledge about serodiscordance, vertical transmission, and male circumcision.

  19. Study of HIV-1 subtypes in serodiscordant couples attending an integrated counselling and testing centre in Mumbai using heteroduplex mobility analysis and DNA sequencing

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    Mehta P

    2010-01-01

    Full Text Available Aims: To determine the prevalent subtypes of HIV-1 in serodiscordant couples. Setting: Integrated Counselling and Testing Centre (ICTC, Department of Microbiology. Study Design: Prospective pilot study. Participants: Thirty HIV-1 serodiscordant couples. Inclusion Criteria: a Documentation of HIV-1 infection in one partner and seronegative status in the other, current history of continued unprotected sexual activity within the partnership, demonstration that they have been in a partnership for at least 1 year and are not currently on highly active antiretroviral therapy HAART; b willingness of both partners to provide written informed consent including consent to continued couple counselling for 3 months. Materials and Methods: HIV-1 subtyping was carried out by heteroduplex mobility analysis (HMA by amplifying env region; and DNA sequencing by amplifying gag region. Results: HIV-1 env gene was amplified successfully in 10/30 samples; gag gene, in 25/30 samples; and both env and gag gene were amplified successfully in 5/30 samples. HIV-1 subtype C was detected from 21 samples; subtype B, from 7; and subtype A, from 2. Sample from 1 positive partner was detected as subtype C by env HMA and subtype B by gag sequencing. Conclusion: HIV-1 subtype C was found to be the predominant subtype of HIV-1 in serodiscordant couples attending our ICTC, followed by HIV-1 subtype B and HIV-1 subtype A, respectively. DNA sequencing was found to be the most reliable method for determining the subtypes of HIV-1.

  20. Experiences Using Pre-Exposure Prophylaxis for Safer Conception Among HIV Serodiscordant Heterosexual Couples in the United States.

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    Bazzi, Angela R; Leech, Ashley A; Biancarelli, Dea L; Sullivan, Meg; Drainoni, Mari-Lynn

    2017-08-01

    Antiretroviral pre-exposure prophylaxis (PrEP) is a promising HIV prevention strategy for HIV serodiscordant couples (HIV-infected male, uninfected female) seeking safer conception. However, most research on PrEP for safer conception has focused on couples in sub-Saharan Africa; little is known about the perspectives or experiences of heterosexual couples in the United States. We conducted qualitative interviews with six couples (six women and five of their male partners) receiving PrEP for conception services at an urban safety net hospital in the US Northeast. In-depth interview guides explored couple relationships and contextual factors and attitudes, perceptions, and decision-making processes surrounding PrEP for safer conception. Thematic analyses focused on identifying the following emergent themes. We found that couple relationships were situated within broader social and cultural contexts of immigration, family, and community that shaped their experiences with HIV and serodiscordant relationship status. Despite strong partner support within relationships, HIV stigma and disapproval of serodiscordant relationships contributed to couples' feelings of social isolation and subsequent aspirations to have "normal" families. By enabling "natural" conception through condomless sex, PrEP for safer conception provided a sense of enhanced relationship intimacy. Couples called for increasing public awareness of PrEP through positive messaging as a way to combat HIV stigma. Findings suggest that relationship dynamics and broader social contexts appear to shape HIV serodiscordant couples' fertility desires and motivations to use PrEP. However, increased public awareness of PrEP for safer conception may be needed to combat HIV stigma at the community level.

  1. Oral Pre-Exposure Prophylaxis (PrEP) for Prevention of HIV in Serodiscordant Heterosexual Couples in the United States: Opportunities and Challenges

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    Myers, Julie E.; Kurth, Ann E.; Cohen, Stephanie E.; Mannheimer, Sharon B.; Simmons, Janie; Pouget, Enrique R.; Trabold, Nicole; Haberer, Jessica E.

    2014-01-01

    Abstract Oral HIV pre-exposure prophylaxis (PrEP) is a promising new biomedical prevention approach in which HIV-negative individuals are provided with daily oral antiretroviral medication for the primary prevention of HIV-1. Several clinical trials have demonstrated efficacy of oral PrEP for HIV prevention among groups at high risk for HIV, with adherence closely associated with level of risk reduction. In the United States (US), three groups have been prioritized for initial implementation of PrEP—injection drug users, men who have sex with men at substantial risk for HIV, and HIV-negative partners within serodiscordant heterosexual couples. Numerous demonstration projects involving PrEP implementation among MSM are underway, but relatively little research has been devoted to study PrEP implementation in HIV-serodiscordant heterosexual couples in the US. Such couples face a unique set of challenges to PrEP implementation at the individual, couple, and provider level with regard to PrEP uptake and maintenance, adherence, safety and toxicity, clinical monitoring, and sexual risk behavior. Oral PrEP also provides new opportunities for serodiscordant couples and healthcare providers for primary prevention and reproductive health. This article provides a review of the critical issues, challenges, and opportunities involved in the implementation of oral PrEP among HIV-serodiscordant heterosexual couples in the US. PMID:25045996

  2. Circumcision of male children for reduction of future risk for HIV: acceptability among HIV serodiscordant couples in Kampala, Uganda.

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    Kenneth K Mugwanya

    Full Text Available The ultimate success of medical male circumcision for HIV prevention may depend on targeting male infants and children as well as adults, in order to maximally reduce new HIV infections into the future.We conducted a cross-sectional study among heterosexual HIV serodiscordant couples (a population at high risk for HIV transmission attending a research clinic in Kampala, Uganda on perceptions and attitudes about medical circumcision for male children for HIV prevention. Correlates of willingness to circumcise male children were assessed using generalized estimating equations methods.318 HIV serodiscordant couples were interviewed, 51.3% in which the female partner was HIV uninfected. Most couples were married and cohabiting, and almost 50% had at least one uncircumcised male child of ≤18 years of age. Overall, 90.2% of male partners and 94.6% of female partners expressed interest in medical circumcision for their male children for reduction of future risk for HIV infection, including 79.9% of men and 87.6% of women who had an uncircumcised male child. Among both men and women, those who were knowledgeable that circumcision reduces men's risk for HIV (adjusted prevalence ratio [APR] 1.34 and 1.14 and those who had discussed the HIV prevention effects of medical circumcision with their partner (APR 1.08 and 1.07 were significantly (p≤0.05 more likely to be interested in male child circumcision for HIV prevention. Among men, those who were circumcised (APR 1.09, p = 0.004 and those who were HIV seropositive (APR 1.09, p = 0.03 were also more likely to be interested in child circumcision for HIV prevention.A high proportion of men and women in Ugandan heterosexual HIV serodiscordant partnerships were willing to have their male children circumcised for eventual HIV prevention benefits. Engaging both parents may increase interest in medical male circumcision for HIV prevention.

  3. Contraception and family planning among HIV-seroconcordant and -serodiscordant couples in the US and Zambia

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    Deborah L Jones

    2010-05-01

    Full Text Available Deborah L Jones1, Olga Villar-Loubet1, Chipepo Kankasa2, Ndashi Chitalu2, Miriam Mumbi2, Stephen M Weiss11Department of Psychiatry and Behavioral Sciences, University of Miami Miller School of Medicine, Miami, FL, USA; 2Department of Paediatrics, University of Zambia School of Medicine, Lusaka, ZambiaAbstract: With the advent of antiretroviral therapy, remarkable progress has been made in the reduction of morbidity and mortality associated with the human immunodeficiency virus (HIV. As a result, in both the developed and developing world, reproductive decision-making and family planning has re-emerged as an important health issue among HIV-seroconcordant and -serodiscordant couples. This study sought to explore contraceptive attitudes and practices among HIV-seropositive and -serodiscordant couples in the US and Zambia and to compare contraceptive decision-making between seroconcordant and discordant couples. Study results suggest that while most participants expressed a willingness to use protection to prevent pregnancy, the majority were not using protection consistently. Similarly, among seropositive younger men in both the US and Zambia, more men expressed a desire to have children than women of either serostatus group. Study outcomes also suggest that male and female condom use to reduce HIV transmission within couples is limited. Thus, as males are largely the sexual decision makers regarding condom use, women’s attitudes or plans regarding child bearing may be eclipsed by those of their male partners, and recent reductions in provision of female condoms in the developing world may further reduce women’s options to protect themselves and prevent pregnancy. Education and counseling on vertical and horizontal transmission of HIV among both seropositive and serodiscordant couples should be an element of family planning efforts. Conversely, family planning should be a critical element of HIV counseling and testing strategies to

  4. HIV seroconversion in a woman preparing for assisted reproduction: an inherent risk in caring for HIV-serodiscordant couples.

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    Sauer, Mark V; Choi, Janet

    2006-03-01

    A woman preparing to undergo IVF and intracytoplasmic sperm injection to avoid horizontal viral transmission of HIV from her seropositive husband was discovered to be HIV seropositive, presumably secondary to a condom break or unprotected intercourse. Had this event occurred after treatment, the sperm-washing technique used to avoid infection would have undoubtedly been called into question. Nearly all HIV-serodiscordant couples are sexually active and therefore at risk for transmitting infection, either due to improper condom use or unprotected intercourse. Physicians willing to treat HIV-serodiscordant couples must accept the inevitability of viral transmission in occasional individuals. Furthermore, it should not be presumed that all patients who experience seroconversions after either intrauterine insemination or IVF procedures do so as a result of inadequacies in the sperm preparation technique.

  5. Fertility Intentions, Pregnancy, and Use of PrEP and ART for Safer Conception Among East African HIV Serodiscordant Couples.

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    Heffron, Renee; Thomson, Kerry; Celum, Connie; Haberer, Jessica; Ngure, Kenneth; Mugo, Nelly; Bukusi, Elizabeth; Katabira, Elly; Odoyo, Josephine; Bulya, Nulu; Asiimwe, Stephen; Tindimwebwa, Edna; Baeten, Jared M

    2017-09-11

    African HIV serodiscordant couples often desire pregnancy, despite sexual HIV transmission risk during pregnancy attempts. Pre-exposure prophylaxis (PrEP) and antiretroviral therapy (ART) reduce HIV risk and can be leveraged for safer conception but how well these strategies are used for safer conception is not known. We conducted an open-label demonstration project of the integrated delivery of PrEP and ART among 1013 HIV serodiscordant couples from Kenya and Uganda followed quarterly for 2 years. We evaluated fertility intentions, pregnancy incidence, the use of PrEP and ART during peri-conception, and peri-conception HIV incidence. At enrollment, 80% of couples indicated a desire for more children. Pregnancy incidence rates were 18.5 and 18.7 per 100 person years among HIV-uninfected and HIV-infected women, and higher among women who recently reported fertility intention (adjusted odds ratio 3.43, 95% CI 2.38-4.93) in multivariable GEE models. During the 6 months preceding pregnancy, 82.9% of couples used PrEP or ART and there were no HIV seroconversions. In this cohort with high pregnancy rates, integrated PrEP and ART was readily used by HIV serodiscordant couples, including during peri-conception periods. Widespread scale-up of safer conception counseling and services is warranted to respond to strong desires for pregnancy among HIV-affected men and women.

  6. A cross-sectional analysis of Trichomonas vaginalis infection among heterosexual HIV-1 serodiscordant African couples.

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    Bochner, Aaron F; Baeten, Jared M; Rustagi, Alison S; Nakku-Joloba, Edith; Lingappa, Jairam R; Mugo, Nelly R; Bukusi, Elizabeth A; Kapiga, Saidi; Delany-Moretlwe, Sinead; Celum, Connie; Barnabas, Ruanne V

    2017-11-01

    Trichomonas vaginalis is the most prevalent curable STI worldwide and has been associated with adverse health outcomes and increased HIV-1 transmission risk. We conducted a cross-sectional analysis among couples to assess how characteristics of both individuals in sexual partnerships are associated with the prevalence of male and female T. vaginalis infection. African HIV-1 serodiscordant heterosexual couples were concurrently tested for trichomoniasis at enrolment into two clinical trials. T. vaginalis testing was by nucleic acid amplification or culture methods. Using Poisson regression with robust standard errors, we identified characteristics associated with trichomoniasis. Among 7531 couples tested for trichomoniasis, 981 (13%) couples contained at least one infected partner. The prevalence was 11% (n=857) among women and 4% (n=319) among men, and most infected individuals did not experience signs or symptoms of T. vaginalis . Exploring concordance of T. vaginalis status within sexual partnerships, we observed that 61% (195/319) of T. vaginalis -positive men and 23% (195/857) of T. vaginalis -positive women had a concurrently infected partner. In multivariable analysis, having a T. vaginalis -positive partner was the strongest predictor of infection for women (relative risk (RR) 4.70, 95% CI 4.10 to 5.38) and men (RR 10.09, 95% CI 7.92 to 12.85). For women, having outside sex partners, gonorrhoea, and intermediate or high Nugent scores for bacterial vaginosis were associated with increased risk of trichomoniasis, whereas age 45 years and above, being married, having children and injectable contraceptive use were associated with reduced trichomoniasis risk. Additionally, women whose male partners were circumcised, had more education or earned income had lower risk of trichomoniasis. We found that within African HIV-1 serodiscordant heterosexual couples, the prevalence of trichomoniasis was high among partners of T. vaginalis -infected individuals, suggesting

  7. HIV transmission risk among HIV seroconcordant and serodiscordant couples: dyadic processes of partner selection.

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    Eaton, Lisa A; West, Tessa V; Kenny, David A; Kalichman, Seth C

    2009-04-01

    Selecting sex partners of the same HIV status or serosorting is a sexual risk reduction strategy used by many men who have sex with men. However, the effectiveness of serosorting for protection against HIV is potentially limited. We sought to examine how men perceive the protective benefits of factors related to serosorting including beliefs about engaging in serosorting, sexual communication, and perceptions of risk for HIV. Participants were 94 HIV negative seroconcordant (same HIV status) couples, 20 HIV serodiscordant (discrepant HIV status) couples, and 13 HIV positive seroconcordant (same HIV status) couples recruited from a large gay pride festival in the southeastern US. To account for nonindependence found in the couple-level data, we used multilevel modeling which includes dyad in the analysis. Findings demonstrated that participants in seroconcordant relationships were more likely to believe that serosorting reduces concerns for condom use. HIV negative participants in seroconcordant relationships viewed themselves at relatively low risk for HIV transmission even though monogamy within relationships and HIV testing were infrequent. Dyadic analyses demonstrated that partners have a substantial effect on an individual's beliefs and number of unprotected sex partners. We conclude that relationship partners are an important source of influence and, thus, intervening with partners is necessary to reduce HIV transmission risks.

  8. Characteristics of HIV-1 discordant couples enrolled in a trial of HSV-2 suppression to reduce HIV-1 transmission: the partners study.

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    Jairam R Lingappa

    Full Text Available The Partners HSV-2/HIV-1 Transmission Study (Partners Study is a phase III, placebo-controlled trial of daily acyclovir for genital herpes (HSV-2 suppression among HIV-1/HSV-2 co-infected persons to reduce HIV-1 transmission to their HIV-1 susceptible partners, which requires recruitment of HIV-1 serodiscordant heterosexual couples. We describe the baseline characteristics of this cohort.HIV-1 serodiscordant heterosexual couples, in which the HIV-1 infected partner was HSV-2 seropositive, had a CD4 count >or=250 cells/mcL and was not on antiretroviral therapy, were enrolled at 14 sites in East and Southern Africa. Demographic, behavioral, clinical and laboratory characteristics were assessed.Of the 3408 HIV-1 serodiscordant couples enrolled, 67% of the HIV-1 infected partners were women. Couples had cohabitated for a median of 5 years (range 2-9 with 28% reporting unprotected sex in the month prior to enrollment. Among HIV-1 susceptible participants, 86% of women and 59% of men were HSV-2 seropositive. Other laboratory-diagnosed sexually transmitted infections were uncommon (500 relative to <350, respectively, p<0.001.The Partners Study successfully enrolled a cohort of 3408 heterosexual HIV-1 serodiscordant couples in Africa at high risk for HIV-1 transmission. Follow-up of this cohort will evaluate the efficacy of acyclovir for HSV-2 suppression in preventing HIV-1 transmission and provide insights into biological and behavioral factors determining heterosexual HIV-1 transmission.ClinicalTrials.gov NCT00194519.

  9. [Vulnerability to HIV infection in serodiscordant couples in Rio de Janeiro, Brazil].

    Science.gov (United States)

    Fernandes, Nilo Martinez; Hennington, Élida Azevedo; Bernardes, Jefferson de Souza; Grinsztejn, Beatriz G

    2017-06-01

    A new era in HIV/AIDS treatment began in 1996 with the advent of highly active antiretroviral therapy (HAART). The advent of these new medicines expanded the treatment resources and improved life expectancy and quality of life for persons living with HIV and AIDS, favoring the maintenance and initiation of relationships between partners with discordant HIV serological status. The main objective of this study with serodiscordant couples was to understand the three dimensions of vulnerability - programmatic, social, and individual - in these couples. The study, belonging to the field of social constructionism, used analysis of discursive practices and production of meanings. Forty in-depth interviews were conducted with couples followed in a clinical research institute. The main results include the lack of information on sexuality in the family and in schools, distorted knowledge on HIV prevention and transmission, inadequacies in HIV testing, and flaws in communicating test results.

  10. Awareness of and willingness to use oral pre-exposure prophylaxis for HIV prevention among HIV-serodiscordant heterosexual couples: a cross-sectional survey in Xinjiang, China.

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    Peierdun Mijiti

    Full Text Available OBJECTIVES: We aimed to investigate the awareness of and willingness to use oral pre-exposure prophylaxis (PrEP for HIV prevention among HIV-negative partners in HIV-serodiscordant heterosexual couples in Xinjiang, China and determine factors that predict willingness to use oral PrEP. METHODS: Between November 2009 and December 2010, a cross-sectional survey was carried out among 351 HIV-negative partners in HIV-serodiscordant heterosexual couples from three cities in Xinjiang, China. Participants completed a self-administered questionnaire to assess their awareness of and willingness to use oral PrEP. Additionally, blood samples were collected to test for HIV infection. Univariate and multivariate logistic regression analyses were performed to identify predictors of willingness to use oral PrEP. RESULTS: Only 10 participants (2.8% reported having heard of PrEP, and only two reported ever using PrEP. However, 297 (84.6% reported that they were willing to use oral PrEP if it was proven to be both safe and effective. Results of multivariate analysis revealed the following independent predictors of willingness to use oral PrEP: monthly household income (adjusted odds ratio = 2.78, <1000 RMB vs. ≥ 1000 RMB, 95% confidence interval: 1.36-5.69, perceived likelihood of contracting HIV from HIV-positive partner (adjusted odds ratio = 2.63, likely vs. unlikely, 95% confidence interval: 1.12-6.19, and worrying about being discriminated against by others due to oral PrEP use (adjusted odds ratio = 9.43, No vs. Yes, 95% confidence interval: 3.78-23.50. CONCLUSIONS: Our results showed HIV-negative partners in HIV-serodiscordant heterosexual couples in China had low awareness of oral PrEP but high willingness to use oral PrEP for HIV prevention. Cost of oral PrEP should be taken into consideration in future PrEP prevention strategy. In addition, efforts should be made to reduce stigma attached to oral PrEP use, which may increase its acceptability among

  11. Estimating the annual risk of HIV transmission within HIV sero-discordant couples in sub-Saharan Africa.

    Science.gov (United States)

    Awad, Susanne F; Chemaitelly, Hiam; Abu-Raddad, Laith J

    2018-01-01

    To estimate the annual risk of HIV transmission (ϕ) within HIV sero-discordant couples in 23 countries in sub-Saharan Africa (SSA), by utilizing newly available national population-based data and accounting for factors known to potentially affect this estimation. We used a recently developed pair-based mathematical model that accommodates for HIV-dynamics temporal variation, sexual risk-behavior heterogeneity, and antiretroviral therapy (ART) scale-up. Estimated country-specific ϕ (in absence of ART) ranged between 4.2% (95% uncertainty interval (UI): 1.9%-6.3%) and 47.4% (95% UI: 37.2%-69.0%) per person-year (ppy), with a median of 12.4%. ϕ was strongly associated with HIV prevalence, with a Pearson correlation coefficient of 0.92, and was larger in high- versus low-HIV-prevalence countries. ϕ increased by 1.31% (95% confidence interval: 1.00%-1.55%) ppy for every 1% increase in HIV prevalence. ϕ estimates were similar to earlier estimates, and suggested considerable heterogeneity in HIV infectiousness across SSA. This heterogeneity may explain, partly, the differences in epidemic scales. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

  12. "I Did Not Want to Give Birth to a Child Who has HIV": Experiences Using PrEP During Pregnancy Among HIV-Uninfected Kenyan Women in HIV-Serodiscordant Couples.

    Science.gov (United States)

    Pintye, Jillian; Beima-Sofie, Kristin M; Kimemia, Grace; Ngure, Kenneth; Trinidad, Susan Brown; Heffron, Renee A; Baeten, Jared M; Odoyo, Josephine; Mugo, Nelly; Bukusi, Elizabeth A; Kelley, Maureen C; John-Stewart, Grace C

    2017-11-01

    The perceptions, motivations, and beliefs of HIV-uninfected women about pre-exposure prophylaxis (PrEP) use during pregnancy can influence its uptake and adherence. This study elicited the views of HIV-uninfected women with personal experience taking PrEP during pregnancy. Qualitative interviews were conducted with HIV-uninfected women who had personal experience taking PrEP while pregnant. Semistructured interviews were conducted with 21 HIV-uninfected Kenyan women in HIV-serodiscordant couples enrolled in an open-label PrEP demonstration project who became pregnant while using PrEP and continued PrEP through their pregnancy. Interviews were audio-recorded and transcribed into English. A qualitative descriptive analysis was performed, using a constant comparison approach to identify key themes related to PrEP use in pregnancy. Desire to remain HIV uninfected and have an HIV-free infant were strong motivators influencing continued use of PrEP during pregnancy. Supporting HIV-infected partners and childbearing within an HIV-serodiscordant relationship were also motivators. Women had challenges distinguishing normal pregnancy symptoms from PrEP side effects and were concerned that observed side effects could be signs of danger for the infant related to PrEP exposure. Health care providers were important conduits of knowledge about PrEP, and continuity of PrEP providers throughout pregnancy facilitated adherence. HIV-uninfected women in HIV-serodiscordant couples were motivated to use PrEP during pregnancy to remain HIV uninfected and to have an HIV-free child but had concerns about side effects. Health care providers will be important for PrEP messaging and adherence support in this unique population.

  13. Possibilities of care for serodiscordant couples for HIV who got pregnant.

    Science.gov (United States)

    Langendorf, Tassiane Ferreira; Souza, Ivis Emília de Oliveira; Padoin, Stela Maris de Mello; Paula, Cristiane Cardoso de; Queiroz, Ana Beatriz Azevedo; Moura, Maria Aparecida Vasconcelos; Melo, Maria Carmen Simões Cardoso de; Silva, Lúcia de Fatima da

    2017-01-01

    Understanding the meaning of pregnancy for heterosexual couples facing serodiscordant situation for HIV, aiming at construction of care possibilities based on subjectivity. Phenomenological research, theoretical-philosophical-methodological framework by Martin Heidegger. Research was conducted in a University Hospital in the countryside of Southern Brazil, from September 2013 to May 2014 through a phenomenological interview, with participation of eleven couples. For the couples, pregnancy is part of life when they wish to have a child, even when one or both of them already have children from previous relationships. In addition, it is part of life when they consider the risks and do not want to have children in such circumstances anymore, but it happened unexpectedly. Understanding reproductive needs and demands of these couples is an aid for qualification and improvement of care as a contribution to nursing care planning towards reproductive health of these couples.

  14. Serodiscordance and disclosure among HIV-positive pregnant women in the Southwestern United States.

    Science.gov (United States)

    Nacius, Lori A; Levison, Judy; Minard, Charles G; Fasser, Carl; Davila, Jessica A

    2013-04-01

    The prevalence of HIV-positive pregnant women in relationships with HIV-negative men in the United States is unclear. The purpose of this study was to calculate the prevalence of HIV-positive pregnant women with a serodiscordant (HIV-negative) partner within a single clinic population, assess disclosure of their HIV status, and examine factors associated with disclosure. All HIV-positive pregnant women who received prenatal care at the Harris County Hospital District Women's Program at Northwest Health Center in Houston TX between 1/1/2006 and 4/1/2011 were identified. Data were obtained from electronic medical records. Prevalence of serodiscordance and disclosure was calculated, and predictors of disclosure were evaluated. We identified 212 HIV-positive pregnant women. About 40% had a serodiscordant partner, and 34% had a partner with an unknown HIV status. Disclosure occurred in over 90% of women with a serodiscordant partner and in 68% of women with partners whose HIV status was unknown. Among pregnant women who knew their HIV status prior to the current pregnancy and had a serodiscordant partner, 92% reported disclosing their status prior to conception. Our data indicated that serodiscordant relationships are common in our clinic population. Suboptimal disclosure rates were observed, especially among women who have a partner with an unknown HIV status. Further research is needed to evaluate the prevalence of serodiscordance and disclosure in other United States populations.

  15. Couples coping with discordant HIV status.

    Science.gov (United States)

    Beckerman, Nancy L

    2002-02-01

    As we start the third decade of the human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) epidemic, how does HIV/AIDS affect the emotional lives of couples of mixed HIV status? This is a case report based on the findings of an exploratory research study of serodiscordant couples in the New York City area. It focuses on the issues confronting a particular couple who represent the salient issues in the lives of serodiscordant couples. This case report discusses the findings of a study that attempted to ascertain the central emotional challenges facing couples of mixed HIV status and discusses one case in particular that illustrates how these issues might commonly manifest themselves. Fear of HIV transmission, coping with uncertainty of potential illness, shifts in emotional intimacy, and dilemmas regarding how HIV has impacted reproductive alternatives were identified as the most commonly experienced emotional issues for the serodiscordant couple.

  16. Possibilities of care for serodiscordant couples for HIV who got pregnant

    Directory of Open Access Journals (Sweden)

    Tassiane Ferreira Langendorf

    Full Text Available ABSTRACT Objective: Understanding the meaning of pregnancy for heterosexual couples facing serodiscordant situation for HIV, aiming at construction of care possibilities based on subjectivity. Method: Phenomenological research, theoretical-philosophical-methodological framework by Martin Heidegger. Research was conducted in a University Hospital in the countryside of Southern Brazil, from September 2013 to May 2014 through a phenomenological interview, with participation of eleven couples. Results: For the couples, pregnancy is part of life when they wish to have a child, even when one or both of them already have children from previous relationships. In addition, it is part of life when they consider the risks and do not want to have children in such circumstances anymore, but it happened unexpectedly. Conclusion: Understanding reproductive needs and demands of these couples is an aid for qualification and improvement of care as a contribution to nursing care planning towards reproductive health of these couples.

  17. Effectiveness of ART and condom use for prevention of sexual HIV transmission in serodiscordant couples: a systematic review and meta-analysis.

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    Huixin Liu

    Full Text Available BACKGROUND: Consistent and correct condom use and suppressive antiretroviral therapy for the infected partner are two of the primary strategies recommended for prevention of heterosexual HIV transmission in serodiscordant couples today. The applied effectiveness of treatment as a prevention strategy in China is still under investigation, and much less is known about its effects in the presence of other prevention strategies such as consistent condom use. METHODS: We conducted a systematic search in PubMed and three Chinese language databases to identify relevant articles for the estimation of relative effectiveness of a consistent condom use and b ART use by index partners for preventing HIV transmission in serodiscordant couples. We also estimated the prevention effectiveness of ART stratified by condom use level and the prevention effectiveness of consistent condom use stratified by ART use level. RESULTS: Pooled results from the eleven eligible studies found a pooled HIV seroconversion incidence of 0.92 cases per 100 person years (PY among HIV-negative spouses whose index partners were taking ART versus 2.45 cases per 100 PY in untreated couples. The IRR comparing seroconversion in couples where the index-partner was on ART versus not on ART was 0.47 (95%CI: 0.43, 0.52, while stratified by condom use, the IRR was 0.33(0.17,0.64. The IRR comparing incidence in couples reporting "consistent condom use" versus those reporting otherwise was 0.02(95%CI:0.01,0.04, after stratified by ART use level, the IRR was 0.01(95%CI: 0.00, 0.06. CONCLUSIONS: ART use by index partners could reduce HIV transmission in serodiscordant couples, and the effectiveness of this prevention strategy could be further increased with consistent condom use.

  18. Gendered differences in the perceived risks and benefits of oral PrEP among HIV-serodiscordant couples in Kenya.

    Science.gov (United States)

    Carroll, Jennifer J; Ngure, Kenneth; Heffron, Renee; Curran, Kathryn; Mugo, Nelly R; Baeten, Jared M

    2016-08-01

    Pre-exposure prophylaxis (PrEP) is effective for preventing HIV among HIV-serodiscordant heterosexual couples. Gender roles may influence perceived personal and social risks related to HIV-prevention behaviors and may affect use of PrEP. In this study, interviews and focus groups were conducted with 68 individuals from 34 mutually disclosed serodiscordant heterosexual partnerships in Thika, Kenya. Sociocultural factors that affect adherence to PrEP were explored using grounded analysis. Three factors were identified, which shape perceptions of PrEP: gendered power dynamics and control over decision-making in the household; conflicts between risk-reduction strategies and male sexual desire; culture-bound definitions of women's work. Adherence to PrEP in the Partners PrEP Study was high; however, participants articulated conflicting interests related to PrEP in connection with traditional gender roles. The successful delivery of PrEP will require understanding of key social factors, particularly related to gender and dyadic dynamics around HIV serostatus.

  19. The challenges to intimacy and sexual relationships for gay men in HIV serodiscordant relationships: a pilot study.

    Science.gov (United States)

    Palmer, R; Bor, R

    2001-10-01

    Human Immunodeficiency Virus (HIV) infection and disease progression create imbalance in long-term, HIV-serodiscordant, gay male relationships, particularly in sexual relations and issues of physical and emotional intimacy. Stage of disease progression and worldview of the couple both affect the relationship and its survival. To redress imbalance, partners employ a range of coping strategies and techniques. This article explores these issues in the context of HIV serodiscordant gay couples and how they preserve their relationships in the face of these unique challenges. For workers who provide psychotherapeutic and community support for people with HIV and for their partners, the results of this study may be helpful in recognizing stress factors for couples, and tailoring support services to the needs of both partners. Overall, this study provides a basis for further work examining the dynamics of serodiscordant relationships.

  20. Attitudes of serodiscordant couples towards antiretroviral-based HIV prevention strategies in Kenya: a qualitative study.

    Science.gov (United States)

    Fowler, Nikola; Arkell, Paul; Abouyannis, Michael; James, Catherine; Roberts, Lesley

    2014-01-01

    Transmission in serodiscordant couples (SDCs) accounts for approximately half of all new HIV infections, both in Kenya and the wider sub-Saharan region (1). With evidence to suggest inconsistent condom use within this population (2), the World Health Organization has recommended two new methods of HIV prevention for SDCs: Treatment as Prevention (TasP) and Pre-Exposure Prophylaxis (PrEP). However, there has been little research about the attitudes of SDCs towards these strategies (3, 4); knowledge that is paramount for successfully predicting the acceptability and efficacy of each method, as well as for informing decisions regarding HIV policy changes in Kenya. An exploratory, qualitative study was conducted in the Muhoroni constituency of Nyando district, Kenya from January to March 2013. Purposive sampling was predominately used to recruit 21 HIV-positive and 17 HIV-negative individuals in a serodiscordant relationship from four hospitals and health centres. During face-to-face semi-structured interviews, topic guides were used to elicit information about participants' attitudes and preferences towards TasP and PrEP. Collected data underwent framework analysis, allowing the development of overarching categories, sub-themes and inductive interpretation. The majority of participants, irrespective of gender and HIV status, found TasP more acceptable than PrEP. A key factor influencing this decision was HIV-negative participants' limited motivation to take and adhere to antiretrovirals (ARVs), primarily due to a predominantly external health locus of control, a lack of cultural acceptance of prophylactic medication and concerns about side effects. In addition to this, the likely health improvements TasP offers HIV-positive partners, as well as the attitude that the sick individual should be the first to receive HIV medication, also contributed to this conclusion. Issues of risk compensation were raised, with some HIV-negative partners indicating a desire to stop

  1. Mediation Analysis of the Efficacy of the Eban HIV/STD Risk-Reduction Intervention for African American HIV Serodiscordant Couples.

    Science.gov (United States)

    El-Bassel, Nabila; Jemmott, John B; Bellamy, Scarlett L; Pequegnat, Willo; Wingood, Gina M; Wyatt, Gail E; Landis, J Richard; Remien, Robert H

    2016-06-01

    Targeting couples is a promising behavioral HIV risk-reduction strategy, but the mechanisms underlying the effects of such interventions are unknown. We report secondary analyses testing whether Social-Cognitive-Theory variables mediated the Eban HIV-risk-reduction intervention's effects on condom-use outcomes. In a multisite randomized controlled trial conducted in four US cities, 535 African American HIV-serodiscordant couples were randomized to the Eban HIV risk-reduction intervention or attention-matched control intervention. Outcomes were proportion condom-protected sex, consistent condom use, and frequency of unprotected sex measured pre-, immediately post-, and 6 and 12 months post-intervention. Potential mediators included Social-Cognitive-Theory variables: outcome expectancies and self-efficacy. Mediation analyses using the product-of-coefficients approach in a generalized-estimating-equations framework revealed that condom-use outcome expectancy, partner-reaction outcome expectancy, intention, self-efficacy, and safer-sex communication improved post-intervention and mediated intervention-induced improvements in condom-use outcomes. These findings underscore the importance of targeting outcome expectancies, self-efficacy, and safer-sex communication in couples-level HIV risk-reduction interventions.

  2. Clinical efficacy of a combination of Percoll continuous density gradient and swim-up techniques for semen processing in HIV-1 serodiscordant couples

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    Osamu Inoue

    2017-01-01

    Full Text Available To evaluate the clinical efficacy of a procedure comprising a combination of Percoll continuous density gradient and modified swim-up techniques for the removal of human immunodeficiency virus type 1 (HIV-1 from the semen of HIV-1 infected males, a total of 129 couples with an HIV-1 positive male partner and an HIV-1 negative female partner (serodiscordant couples who were treated at Keio University Hospital between January 2002 and April 2012 were examined. A total of 183 ejaculates from 129 HIV-1 infected males were processed. After swim-up, we successfully collected motile sperms at a recovery rate as high as 100.0% in cases of normozoospermia (126/126 ejaculates, oligozoospermia (6/6, and asthenozoospermia (36/36. The recovery rate of oligoasthenozoospermia was 86.7% (13/15. In processed semen only four ejaculates (4/181:2.2% showed viral nucleotide sequences consistent with those in the blood of the infected males. After using these sperms, no horizontal infections of the female patients and no vertical infections of the newborns were observed. Furthermore, no obvious adverse effects were observed in the offspring. This protocol allowed us to collect HIV-1 negative motile sperms at a high rate, even in male factor cases. We concluded that our protocol is clinically effective both for decreasing HIV-1 infections and for yielding a healthy child.

  3. Absence of transmission from HIV-infected individuals with HAART to their heterosexual serodiscordant partners.

    Science.gov (United States)

    Del Romero, Jorge; Río, Isabel; Castilla, Jesús; Baza, Begoña; Paredes, Vanessa; Vera, Mar; Rodríguez, Carmen

    2015-12-01

    Further studies are needed to evaluate the level of effectiveness and durability of HAART to reduce the risk of HIV sexual transmission in serodiscordant couples having unprotected sexual practices. A cross-sectional study was conducted with prospective cohort of heterosexual HIV serodiscordant couples where the only risk factor for HIV transmission to the uninfected partner (sexual partner) was the sexual relationship with the infected partner (index case). HIV prevalence in sexual partners at enrolment and seroconversions in follow-up were compared by antiretroviral treatment in the index partner, HIV plasma viral load in index cases and sexual risk exposures in sexual partners. In each visit, an evaluation of the risks for HIV transmission, preventive counselling and screening for genitourinary infections in the sexual partner was performed, as well as the determination of the immunological and virological situation and antiretroviral treatment in the index case. At enrolment no HIV infection was detected in 202 couples where the index case was taking HAART. HIV prevalence in sexual partners was 9.6% in 491 couples where the index case was not taking antiretroviral treatment (p<0.001). During follow-up there was no HIV seroconversion among 199 partners whose index case was taking HAART, accruing 7600 risky sexual exposures and 85 natural pregnancies. Among 359 couples whose index case was not under antiretroviral treatment, over 13,000 risky sexual exposures and 5 HIV seroconversions of sexual partners were recorded. The percentage of seroconversion among couples having risky sexual intercourse was 2.5 (95% confidence interval [CI]: 1.1-5.6) when the index case did not undergo antiretroviral treatment and zero (95% CI: 0-3.2) when the index case received HAART. The risk of sexual transmission of HIV from individuals with HAART to their heterosexual partners can become extremely low. Copyright © 2014. Published by Elsevier España, S.L.U.

  4. Adherence to antiretroviral prophylaxis for HIV prevention: a substudy cohort within a clinical trial of serodiscordant couples in East Africa.

    Science.gov (United States)

    Haberer, Jessica E; Baeten, Jared M; Campbell, James; Wangisi, Jonathan; Katabira, Elly; Ronald, Allan; Tumwesigye, Elioda; Psaros, Christina; Safren, Steven A; Ware, Norma C; Thomas, Katherine K; Donnell, Deborah; Krows, Meighan; Kidoguchi, Lara; Celum, Connie; Bangsberg, David R

    2013-01-01

    Randomized clinical trials of oral antiretroviral pre-exposure prophylaxis (PrEP) for HIV prevention have widely divergent efficacy estimates, ranging from 0% to 75%. These discrepancies are likely due to differences in adherence. To our knowledge, no studies to date have examined the impact of improving adherence through monitoring and/or intervention, which may increase PrEP efficacy, or reported on objective behavioral measures of adherence, which can inform PrEP effectiveness and implementation. Within the Partners PrEP Study (a randomized placebo-controlled trial of oral tenofovir and emtricitabine/tenofovir among HIV-uninfected members of serodiscordant couples in Kenya and Uganda), we collected objective measures of PrEP adherence using unannounced home-based pill counts and electronic pill bottle monitoring. Participants received individual and couples-based adherence counseling at PrEP initiation and throughout the study; counseling was intensified if unannounced pill count adherence fell to counseling, and HIV testing. A total of 1,147 HIV-uninfected participants were enrolled: 53% were male, median age was 34 years, and median partnership duration was 8.5 years. Fourteen HIV infections occurred among adherence study participants--all of whom were assigned to placebo (PrEP efficacy = 100%, 95% confidence interval 83.7%-100%, pmarriage were associated with >80% adherence. Study limitations include potential shortcomings of the adherence measures and use of a convenience sample within the substudy cohort. The high PrEP adherence achieved in the setting of active adherence monitoring and counseling support was associated with a high degree of protection from HIV acquisition by the HIV-uninfected partner in heterosexual serodiscordant couples. Low PrEP adherence was associated with sexual behavior, alcohol use, younger age, and length of PrEP use. Please see later in the article for the Editors' Summary.

  5. Intimacy and sexual risk behaviour in serodiscordant male couples.

    Science.gov (United States)

    Remien, R H; Carballo-Diéguez, A; Wagner, G

    1995-01-01

    Several studies have demonstrated individual-level determinants of HIV sexual risk behaviour. Very little research has been conducted to identify couple-level factors associated with unsafe sexual behaviour. As part of a three-year study of more than 100 serodiscordant male couples, we conducted an in-depth qualitative study of 15 Latino and non-Latino male couples via focus groups and a follow-up telephone survey. We identified the sexual risk behaviour that occurs in these male couples, their perceptions of susceptibility for HIV transmission, and numerous couple-level and intrapsychic factors associated with their risk behaviour. We also describe the challenges confronted by these couples and barriers to emotional intimacy and couple satisfaction. Finally, we provide suggestions for ways of intervening to facilitate improved couple functioning, pleasure, satisfaction, and communication, and ways of reducing sexual risk behaviour without loss of emotional intimacy.

  6. Adherence to antiretroviral prophylaxis for HIV prevention: a substudy cohort within a clinical trial of serodiscordant couples in East Africa.

    Directory of Open Access Journals (Sweden)

    Jessica E Haberer

    Full Text Available Randomized clinical trials of oral antiretroviral pre-exposure prophylaxis (PrEP for HIV prevention have widely divergent efficacy estimates, ranging from 0% to 75%. These discrepancies are likely due to differences in adherence. To our knowledge, no studies to date have examined the impact of improving adherence through monitoring and/or intervention, which may increase PrEP efficacy, or reported on objective behavioral measures of adherence, which can inform PrEP effectiveness and implementation.Within the Partners PrEP Study (a randomized placebo-controlled trial of oral tenofovir and emtricitabine/tenofovir among HIV-uninfected members of serodiscordant couples in Kenya and Uganda, we collected objective measures of PrEP adherence using unannounced home-based pill counts and electronic pill bottle monitoring. Participants received individual and couples-based adherence counseling at PrEP initiation and throughout the study; counseling was intensified if unannounced pill count adherence fell to 80% adherence. Study limitations include potential shortcomings of the adherence measures and use of a convenience sample within the substudy cohort.The high PrEP adherence achieved in the setting of active adherence monitoring and counseling support was associated with a high degree of protection from HIV acquisition by the HIV-uninfected partner in heterosexual serodiscordant couples. Low PrEP adherence was associated with sexual behavior, alcohol use, younger age, and length of PrEP use. Please see later in the article for the Editors' Summary.

  7. Alignment of adherence and risk for HIV acquisition in a demonstration project of pre-exposure prophylaxis among HIV serodiscordant couples in Kenya and Uganda: a prospective analysis of prevention-effective adherence.

    Science.gov (United States)

    Haberer, Jessica E; Kidoguchi, Lara; Heffron, Renee; Mugo, Nelly; Bukusi, Elizabeth; Katabira, Elly; Asiimwe, Stephen; Thomas, Katherine K; Celum, Connie; Baeten, Jared M

    2017-07-25

    Adherence is essential for pre-exposure prophylaxis (PrEP) to protect against HIV acquisition, but PrEP use need not be life-long. PrEP is most efficient when its use is aligned with periods of risk - a concept termed prevention-effective adherence. The objective of this paper is to describe prevention-effective adherence and predictors of adherence within an open-label delivery project of integrated PrEP and antiretroviral therapy (ART) among HIV serodiscordant couples in Kenya and Uganda (the Partners Demonstration Project). We offered PrEP to HIV-uninfected participants until the partner living with HIV had taken ART for ≥6 months (a strategy known as "PrEP as a bridge to ART"). The level of adherence sufficient to protect against HIV was estimated in two ways: ≥4 and ≥6 doses/week (per electronic monitoring). Risk for HIV acquisition was considered high if the couple reported sex with 25 years, older male partners and desire for relationship success. Predictors of not achieving sufficient adherence were no longer being a couple, delayed PrEP initiation, >6 months  of follow-up, ART use >6 months  by the partner living with HIV and problem alcohol use. Over three-quarters of participant-visits by HIV-uninfected partners in serodiscordant couples achieved prevention-effective adherence with PrEP. Greater adherence was observed during months with HIV risk and the strongest predictor of achieving sufficient adherence was sexual activity.

  8. Risky sexual behaviours among HIV Sero-discordant individuals ...

    African Journals Online (AJOL)

    Backgound: HIV/AIDS pandemic is a great public health concern hence the need to identify interventions to prevent new infections among risk groups. Objective: To determine risky sexual behaviours among HIV sero-discordant individuals attending Defence Forces Memorial Hospital (DFMH). Design: A descriptive ...

  9. Characterizing HIV epidemiology in stable couples in Cambodia, the Dominican Republic, Haiti, and India.

    Science.gov (United States)

    Chemaitelly, H; Abu-Raddad, L J

    2016-01-01

    Using a set of statistical methods and HIV mathematical models applied on nationally representative Demographic and Health Survey data, we characterized HIV serodiscordancy patterns and HIV transmission dynamics in stable couples (SCs) in four countries: Cambodia, the Dominican Republic, Haiti, and India. The majority of SCs affected by HIV were serodiscordant, and about a third of HIV-infected persons had uninfected partners. Overall, nearly two-thirds of HIV infections occurred in individuals in SCs, but only about half of these infections were due to transmissions within serodiscordant couples. The majority of HIV incidence in the population occurred through extra-partner encounters in SCs. There is similarity in HIV epidemiology in SCs between these countries and countries in sub-Saharan Africa, despite the difference in scale of epidemics. It appears that HIV epidemiology in SCs may share similar patterns globally, possibly because it is a natural 'spillover' effect of HIV dynamics in high-risk populations.

  10. HIV-1 transmission linkage in an HIV-1 prevention clinical trial

    Energy Technology Data Exchange (ETDEWEB)

    Leitner, Thomas [Los Alamos National Laboratory; Campbell, Mary S [UNIV OF WASHINGTON; Mullins, James I [UNIV OF WASHINGTON; Hughes, James P [UNIV OF WASHINGTON; Wong, Kim G [UNIV OF WASHINGTON; Raugi, Dana N [UNIV OF WASHINGTON; Scrensen, Stefanie [UNIV OF WASHINGTON

    2009-01-01

    HIV-1 sequencing has been used extensively in epidemiologic and forensic studies to investigate patterns of HIV-1 transmission. However, the criteria for establishing genetic linkage between HIV-1 strains in HIV-1 prevention trials have not been formalized. The Partners in Prevention HSV/HIV Transmission Study (ClinicaITrials.gov NCT00194519) enrolled 3408 HIV-1 serodiscordant heterosexual African couples to determine the efficacy of genital herpes suppression with acyclovir in reducing HIV-1 transmission. The trial analysis required laboratory confirmation of HIV-1 linkage between enrolled partners in couples in which seroconversion occurred. Here we describe the process and results from HIV-1 sequencing studies used to perform transmission linkage determination in this clinical trial. Consensus Sanger sequencing of env (C2-V3-C3) and gag (p17-p24) genes was performed on plasma HIV-1 RNA from both partners within 3 months of seroconversion; env single molecule or pyrosequencing was also performed in some cases. For linkage, we required monophyletic clustering between HIV-1 sequences in the transmitting and seroconverting partners, and developed a Bayesian algorithm using genetic distances to evaluate the posterior probability of linkage of participants sequences. Adjudicators classified transmissions as linked, unlinked, or indeterminate. Among 151 seroconversion events, we found 108 (71.5%) linked, 40 (26.5%) unlinked, and 3 (2.0%) to have indeterminate transmissions. Nine (8.3%) were linked by consensus gag sequencing only and 8 (7.4%) required deep sequencing of env. In this first use of HIV-1 sequencing to establish endpoints in a large clinical trial, more than one-fourth of transmissions were unlinked to the enrolled partner, illustrating the relevance of these methods in the design of future HIV-1 prevention trials in serodiscordant couples. A hierarchy of sequencing techniques, analysis methods, and expert adjudication contributed to the linkage

  11. Motivators, concerns, and barriers to adoption of pre-exposure prophylaxis for HIV prevention among gay and bisexual men in HIV serodiscordant male relationships

    Science.gov (United States)

    Brooks, Ronald A.; Kaplan, Rachel L.; Lieber, Eli; Landovitz, Raphael J.; Lee, Sung-Jae; Leibowitz, Arleen A.

    2011-01-01

    The purpose of this study was to identify factors that may facilitate or impede future adoption of pre-exposure prophylaxis (PrEP) for HIV prevention among gay and bisexual men in HIV-serodiscordant relationships. This qualitative study utilized semi-structured interviews conducted with a multi-racial/ethnic sample of 25 gay and bisexual HIV serodiscordant male couples (n=50 individuals) recruited from community settings in Los Angeles, California. A modified grounded theory approach was employed to identify major themes relating to future adoption of PrEP for HIV prevention. Motivators for adoption included protection against HIV infection, less concern and fear regarding HIV transmission, the opportunity to engage in unprotected sex, and endorsements of PrEP’s effectiveness. Concerns and barriers to adoption included the cost of PrEP, short- and long-term side effects, adverse effects of intermittent use or discontinuing PrEP, and accessibility of PrEP. The findings suggest the need for a carefully planned implementation program along with educational and counseling interventions in the dissemination of an effective PrEP agent. PMID:21476147

  12. Variations in KIR Genes: A Study in HIV-1 Serodiscordant Couples

    Directory of Open Access Journals (Sweden)

    Vijay R. Chavan

    2014-01-01

    Full Text Available Background. NK cells have anti-HIV activity mediated through killer cell immunoglobulin-like receptors (KIRs. The current prospective cohort study evaluated whether variation in KIR genes is associated with HIV infection in discordant couples (DCs, where one spouse remains seronegative (HSN despite repeated exposure to the HIV. Methods. KIR was genotyped using PCR SSP. Viral load and CD4 counts were estimated using commercially available reagents. Data were analyzed using SPSS software. Results. Among the 47 DCs, HSN spouses had significantly (P=0.006 higher frequencies of KIR3DS1. Regression analysis revealed significant (P=0.009 association of KIR2DS1 with low viral load. KIR2DS4 variant was associated (P=0.032 with high viral load. Three pairs of KIR genes were in strong LD in HSNs and two pairs in HSPs. There were 60 KIR genotypes, and 16 are reported the first time in the Indian population. Exclusive genotypes were present either in HSPs (N=22, 11 unique genotypes or in HSNs (n=27, 9 unique genotypes. Conclusions. This study highlights for the first time in the Indian population an association of KIR genes in HIV infection where presence of exclusive and unique genotypes indicates possible association with either HIV infection or with protection.

  13. HIV status awareness, partnership dissolution and HIV transmission in generalized epidemics.

    Science.gov (United States)

    Reniers, Georges; Armbruster, Benjamin

    2012-01-01

    HIV status aware couples with at least one HIV positive partner are characterized by high separation and divorce rates. This phenomenon is often described as a corollary of couples HIV Testing and Counseling (HTC) that ought to be minimized. In this contribution, we demonstrate the implications of partnership dissolution in serodiscordant couples for the propagation of HIV. We develop a compartmental model to study epidemic outcomes of elevated partnership dissolution rates in serodiscordant couples and parameterize it with estimates from population-based data (Rakai, Uganda). Via its effect on partnership dissolution, every percentage point increase in HIV status awareness reduces HIV incidence in monogamous populations by 0.27 percent for women and 0.63 percent for men. These effects are even larger when the assumption of monogamy can be relaxed, but are moderated by other behavior changes (e.g., increased condom use) in HIV status aware serodiscordant partnerships. When these behavior changes are taken into account, each percentage point increase in HIV status awareness reduces HIV incidence by 0.13 and 0.32 percent for women and men, respectively (assuming monogamy). The partnership dissolution effect exists because it decreases the fraction of serodiscordant couples in the population and prolongs the time that individuals spend outside partnerships. Our model predicts that elevated partnership dissolution rates in HIV status aware serodiscordant couples reduce the spread of HIV. As a consequence, the full impact of couples HTC for HIV prevention is probably larger than recognized to date. Particularly high partnership dissolution rates in female positive serodiscordant couples contribute to the gender imbalance in HIV infections.

  14. A randomized controlled trial to promote long-term contraceptive use among HIV-serodiscordant and concordant positive couples in Zambia.

    Science.gov (United States)

    Stephenson, Rob; Vwalika, Bellington; Greenberg, Lauren; Ahmed, Yusuf; Vwalika, Cheswa; Chomba, Elwyn; Kilembe, William; Tichacek, Amanda; Allen, Susan

    2011-04-01

    Countries facing high HIV prevalence often also experience high levels of fertility and low contraceptive use, suggesting high levels of unmet need for contraceptive services. In particular, the unique needs of couples with one or both partners HIV positive are largely missing from many current family planning efforts, which focus on the prevention of pregnancies in the absence of reduction of the risk of HIV and other sexually transmitted infections (STIs). This article presents an examination of contraceptive method uptake among a cohort of HIV serodiscordant and concordant positive study participants in Zambia. Baseline contraceptive use was low; however, exposure to a video-based intervention that provided information on contraceptive methods and modeled desirable future planning behaviors dramatically increased the uptake of modern contraceptive methods. Including information on family planning in voluntary counseling and testing (VCT) services in addition to tailoring the delivery of family planning information to meet the needs and concerns of HIV-positive women or those with HIV-positive partners is an essential step in the delivery of services and prevention efforts to reduce the transmission of HIV. Family planning and HIV prevention programs should integrate counseling on dual method use, combining condoms for HIV/STI prevention with a long-acting contraceptive for added protection against unplanned pregnancy.

  15. "Since both of us are using antiretrovirals, we have been supportive to each other": facilitators and barriers of pre-exposure prophylaxis use in heterosexual HIV serodiscordant couples in Kisumu, Kenya.

    Science.gov (United States)

    Patel, Rena C; Stanford-Moore, Gaelen; Odoyo, Josephine; Pyra, Maria; Wakhungu, Imeldah; Anand, Keerthana; Bukusi, Elizabeth A; Baeten, Jared M; Brown, Joelle M

    2016-01-01

    Since 2015, the World Health Organization recommends pre-exposure prophylaxis (PrEP) for all persons at substantial risk for HIV, including HIV-uninfected partners in serodiscordant relationships in resource-limited settings. As PrEP moves from clinical trials to real-world use, understanding facilitators of and barriers to PrEP initiation and adherence is critical to successful PrEP implementation and rollout. We conducted 44 in-depth individual or couple interviews with 63 participants (30 without HIV and 33 with HIV) enrolled in the Partners Demonstration Project in Kisumu, Kenya, between August and September 2014. The semi-structured interviews discussed the following: 1) perceived advantages and disadvantages of antiretroviral therapy (ART)/PrEP; 2) reasons for accepting or declining ART/PrEP and 3) influence of prevention of transmission to partner or infant on ART/PrEP use. Transcripts from the interviews were iteratively analyzed using inductive content analysis. Our study identified three key factors that may facilitate initiation of PrEP in this population. First, participants using PrEP felt reduced stress and increased trust in their HIV serodiscordant relationships. Second, greater community-wide knowledge of PrEP was thought to likely increase PrEP acceptance. Third, greater education and counselling by providers on PrEP use was also considered to likely increase the adoption of PrEP. We also identified three key barriers to initiation of and adherence to PrEP. First, most participants who declined PrEP expressed doubts about the relative additional effectiveness of PrEP in combination with other prevention tools. Second, perceived stigma related to PrEP use was an important barrier to PrEP initiation. Third, many struggled with overcoming perceived side effects or logistical challenges of taking daily PrEP, particularly when they themselves were not ill. Leveraging the facilitators and overcoming barriers to PrEP uptake may enhance the successful

  16. Contraceptive method and pregnancy incidence among women in HIV-1-serodiscordant partnerships.

    Science.gov (United States)

    Ngure, Kenneth; Heffron, Renee; Mugo, Nelly R; Celum, Connie; Cohen, Craig R; Odoyo, Josephine; Rees, Helen; Kiarie, James N; Were, Edwin; Baeten, Jared M

    2012-02-20

    Effective contraception reduces unintended pregnancies and is a central strategy to reduce vertical HIV-1 transmission for HIV-1-infected women. Among 2269 HIV-1-seropositive and 1085-seronegative women from seven African countries who were members of HIV-1-serodiscordant heterosexual partnerships and who were participating in an HIV-1 prevention clinical trial, we assessed pregnancy incidence according to contraceptive method using multivariate Andersen-Gill analysis. Compared with women using no contraceptive method, pregnancy incidence was significantly reduced among HIV-1-seropositive and HIV-1-seronegative women using injectable contraception [adjusted hazard ratio (aHR) 0.24, P = 0.001 and aHR 0.25, P pregnancy risk only among HIV-1-seropositive women (aHR 0.51, P = 0.004) but not seronegative women (aHR 0.64, P = 0.3), and, for both seropositive and seronegative women, oral contraceptive pill users were more likely to become pregnant than injectable contraceptive users (aHR 2.22, P = 0.01 for HIV-1-seropositive women and aHR 2.65, P = 0.09 for HIV-1-seronegative women). Condoms, when reported as being used as the primary contraceptive method, marginally reduced pregnancy incidence (aHR 0.85, P = 0.1 for seropositive women and aHR 0.67, P = 0.02 for seronegative women). There were no pregnancies among women using intrauterine devices, implantable methods or who had undergone surgical sterilization, although these methods were used relatively infrequently. Family planning programs and HIV-1 prevention trials need innovative ways to motivate uptake and sustained use of longer acting, less user-dependent contraception for women who do not desire pregnancy.

  17. HIV status awareness, partnership dissolution and HIV transmission in generalized epidemics.

    Directory of Open Access Journals (Sweden)

    Georges Reniers

    Full Text Available HIV status aware couples with at least one HIV positive partner are characterized by high separation and divorce rates. This phenomenon is often described as a corollary of couples HIV Testing and Counseling (HTC that ought to be minimized. In this contribution, we demonstrate the implications of partnership dissolution in serodiscordant couples for the propagation of HIV.We develop a compartmental model to study epidemic outcomes of elevated partnership dissolution rates in serodiscordant couples and parameterize it with estimates from population-based data (Rakai, Uganda.Via its effect on partnership dissolution, every percentage point increase in HIV status awareness reduces HIV incidence in monogamous populations by 0.27 percent for women and 0.63 percent for men. These effects are even larger when the assumption of monogamy can be relaxed, but are moderated by other behavior changes (e.g., increased condom use in HIV status aware serodiscordant partnerships. When these behavior changes are taken into account, each percentage point increase in HIV status awareness reduces HIV incidence by 0.13 and 0.32 percent for women and men, respectively (assuming monogamy. The partnership dissolution effect exists because it decreases the fraction of serodiscordant couples in the population and prolongs the time that individuals spend outside partnerships.Our model predicts that elevated partnership dissolution rates in HIV status aware serodiscordant couples reduce the spread of HIV. As a consequence, the full impact of couples HTC for HIV prevention is probably larger than recognized to date. Particularly high partnership dissolution rates in female positive serodiscordant couples contribute to the gender imbalance in HIV infections.

  18. Analysis of Social and Genetic Factors Influencing Heterosexual Transmission of HIV within Serodiscordant Couples in the Henan Cohort.

    Science.gov (United States)

    Zhu, Qian; Zhu, Peng; Zhang, Yilei; Li, Jie; Ma, Xuejun; Li, Ning; Wang, Qi; Xue, Xiujuan; Luo, Le; Li, Zizhao; Ring, Huijun Z; Ring, Brian Z; Su, Li

    2015-01-01

    There is considerable variability between individuals in susceptibility to infection by human immunodeficiency virus (HIV). Many social, clinical and genetic factors are known to contribute to the likelihood of HIV transmission, but there is little consensus on the relative importance and potential interaction of these factors. Additionally, recent studies of several variants in chemokine receptors have identified alleles that may be predictive of HIV transmission and disease progression; however the strengths and directions of the associations of these genetic markers with HIV transmission have markedly varied between studies. To better identify factors that predict HIV transmission in a Chinese population, 180 cohabiting serodiscordant couples were enrolled for study by the Henan Center for Disease Prevention and Control, and transmission and progression of HIV infection were regularly measured. We found that anti-retroviral therapy, education level, and condom use were the most significant factors in determining likelihood of HIV transmission in this study. We also assessed ten variants in three genes (CXCL12, CCR2, and CCR5) that have been shown to influence HIV transmission. We found two tightly linked variants in CCR2 and CCR5, rs1799864 and rs1800024, have a significant positive association with transmission as recessive models (OR>10, P value=0.011). Mixed effects models showed that these genetic variants both retained significance when assessed with either treatment or condom use. These markers of transmission susceptibility may therefore serve to help stratify individuals by risk for HIV transmission.

  19. Analysis of Social and Genetic Factors Influencing Heterosexual Transmission of HIV within Serodiscordant Couples in the Henan Cohort.

    Directory of Open Access Journals (Sweden)

    Qian Zhu

    Full Text Available There is considerable variability between individuals in susceptibility to infection by human immunodeficiency virus (HIV. Many social, clinical and genetic factors are known to contribute to the likelihood of HIV transmission, but there is little consensus on the relative importance and potential interaction of these factors. Additionally, recent studies of several variants in chemokine receptors have identified alleles that may be predictive of HIV transmission and disease progression; however the strengths and directions of the associations of these genetic markers with HIV transmission have markedly varied between studies. To better identify factors that predict HIV transmission in a Chinese population, 180 cohabiting serodiscordant couples were enrolled for study by the Henan Center for Disease Prevention and Control, and transmission and progression of HIV infection were regularly measured. We found that anti-retroviral therapy, education level, and condom use were the most significant factors in determining likelihood of HIV transmission in this study. We also assessed ten variants in three genes (CXCL12, CCR2, and CCR5 that have been shown to influence HIV transmission. We found two tightly linked variants in CCR2 and CCR5, rs1799864 and rs1800024, have a significant positive association with transmission as recessive models (OR>10, P value=0.011. Mixed effects models showed that these genetic variants both retained significance when assessed with either treatment or condom use. These markers of transmission susceptibility may therefore serve to help stratify individuals by risk for HIV transmission.

  20. Sexual life and fertility desire in long-term HIV serodiscordant couples in Addis Ababa, Ethiopia: a grounded theory study

    Directory of Open Access Journals (Sweden)

    Hailemariam Tewodros G

    2012-10-01

    Full Text Available Abstract Background Even though remarkable progress has been achieved, HIV/AIDS continues to be a major global health priority. HIV discordant relationship is one of the emerging issues in HIV prevention endeavour. In Ethiopia, very little is known about HIV-serodiscordant couples particularly how they manage their sexual relationship and fertility desire. Therefore, we conduct this study with the aim of exploring the experiences of HIV discordant couples about their sexual life, and fertility desire in the context of long-term relationships in Addis Ababa, Ethiopia. Methods A grounded theory approach was employed using in-depth interviews among 36 informants in ART/PMTCT centers of three public hospitals, a health center and one PLHIV association in Addis Ababa. Theoretical sampling was used to recruit 28 clients who lived in a discordant relationship and eight health care providers as key informants. Data collection and analysis were undertaken simultaneously using a constant comparison. The analysis was facilitated using OpenCode software. Results A grounded theory pertaining to sexual life and desire to have a child among HIV discordant couples emerged as “maintaining the relationship” as a core category. Couples pass through a social process of struggle to maintain their relationship. The causal conditions for couples to enter into the process of struggle to maintain their relationship were collectively categorized as “Entering in-to a transition” (knowing HIV serostatus and this includes mismatch of desire to have a child, controversy on safe sex versus desire to have a child, and undeniable change in sexual desire and practice through time were the features in entering into-transition. Then after the transition, couples engaged in certain actions/strategies that are categorized as “dealing with discordancy” such as entertaining partner’s interest by scarifying once self interest to maintain their relationship. Conclusions

  1. Contraceptive method and pregnancy incidence among African women in HIV-1 serodiscordant partnerships

    Science.gov (United States)

    NGURE, Kenneth; HEFFRON, Renee; MUGO, Nelly R.; CELUM, Connie; COHEN, Craig R.; ODOYO, Josephine; REES, Helen; KIARIE, James N.; WERE, Edwin; BAETEN, Jared M.

    2014-01-01

    Background Effective contraception reduces unintended pregnancies and is a central strategy to reduce vertical HIV-1 transmission for HIV-1 infected women. Methods Among 2269 HIV-1 seropositive and 1085 seronegative women from 7 African countries who were members of HIV-1 serodiscordant heterosexual partnerships and who were participating in an HIV-1 prevention clinical trial, we assessed pregnancy incidence for women using various contraceptive methods using multivariate Andersen-Gill analysis. Results Compared with women using no contraceptive method, pregnancy incidence was significantly reduced among HIV-1 seropositive and seronegative women using injectable contraception (adjusted hazard ratio (aHR) 0.24, p=0.001 and aHR 0.25, ppregnancy risk only among HIV-1 seropositive women (aHR 0.51, p=0.004) but not seronegative women (aHR 0.64, p=0.3), and, for both seropositive and seronegative women, oral contraceptive pill users were more likely to become pregnant than injectable contraceptive users (aHR 2.22, p=0.01 for HIV-1 seropositive women and aHR 2.65, p=0.09 for HIV-1 seronegative women). Condoms, when reported as being used as the primary contraceptive method, marginally reduced pregnancy incidence (aHR 0.85, p=0.1 for seropositive women and aHR 0.67, p=0.02 for seronegative women). There were no pregnancies among women using intrauterine devices, implantable methods or who had undergone surgical sterilization, although these methods were used relatively infrequently. Conclusions Family planning programs and HIV-1 prevention trials need innovative ways to motivate uptake and sustained use of longer acting, less user-dependent contraception for women who do not desire pregnancy. PMID:22156966

  2. Quality of life and related factors among HIV-positive spouses from serodiscordant couples under antiretroviral therapy in Henan Province, China.

    Directory of Open Access Journals (Sweden)

    Duo Shan

    Full Text Available OBJECTIVE: To describe the quality of life and related factors in HIV-positive spouses undergoing ART from discordant couples. METHODS: A cross-sectional study was conducted among 1,009 HIV-positive spouses from serodiscordant couples in Zhumadian, Henan Province, between October 1, 2008 and March 31, 2009. HIV-positive spouses were interviewed by local health professionals. Quality of life was evaluated by WHOQOL (Chinese Version. A multiple linear regression model was used to analyze the related factors. RESULTS: The majority of subjects were female (56.39%, had received a high school education (44%, were of Han ethnicity (98.41%, and were farmers (90.09%; the median time period of receiving ART was 3.92 years. The physical, psychological, social, and environmental QOL scores of the subjects were 12.91±1.95, 12.35±1.80, 13.96±2.43, and 12.45±1.91 respectively. The multiple linear regression model identified the physical domain related factors to be CD4 count, educational level, and occupation; psychological domain related factors include age, educational level, and reported STD symptom; social domain related factors included education level; and environmental domain related factors included education level, reported STD symptoms, and occupation. CONCLUSION: Being younger, a farmer, having a lower level of education, a reported STD symptom, or lower CD4 count, could decrease one's quality of life, suggesting that the use of blanket ART programs alone may not necessarily improve quality of life. Subjects received lower scores in the psychological domain, suggesting that psychological intervention may also need to be strengthened.

  3. Erratum to: Risky Sex and HIV Acquisition Among HIV Serodiscordant Couples in Zambia, 2002-2012: What Does Alcohol Have To Do With It?

    Science.gov (United States)

    Joseph Davey, Dvora; Kilembe, William; Wall, Kristin M; Khu, Naw Htee; Brill, Ilene; Vwalika, Bellington; Chomba, Elwyn; Mulenga, Joseph; Tichacek, Amanda; Javanbakht, Marjan; Comulada, W Scott; Allen, Susan; Gorbach, Pamina M

    2017-09-27

    The article Risky Sex and HIV Acquisition Among HIV Serodiscordant Couples in Zambia, 2002-2012: What Does Alcohol Have To Do With It?, written by Dvora Joseph Davey, William Kilembe, Kristin M. Wall, Naw Htee Khu, Ilene Brill, Bellington Vwalika, Elwyn Chomba, Joseph Mulenga, Amanda Tichacek, Marjan Javanbakht, W. Scott Comulada, Susan Allen, Pamina M. Gorbach, was originally published Online First without open access. After publication in volume 21, issue 7, pages 1892-1903, the author decided to opt for Open Choice and to make the article an open access publication. Therefore, the copyright of the article has been changed to © The Author(s) [Year] and the article is forthwith distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/ ), which permits use, duplication, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

  4. Reproductive Counseling by Clinic Healthcare Workers in Durban, South Africa: Perspectives from HIV-Infected Men and Women Reporting Serodiscordant Partners

    Directory of Open Access Journals (Sweden)

    L. T. Matthews

    2012-01-01

    Full Text Available Background. Understanding HIV-infected patient experiences and perceptions of reproductive counseling in the health care context is critical to inform design of effective pharmaco-behavioral interventions that minimize periconception HIV risk and support HIV-affected couples to realize their fertility goals. Methods. We conducted semistructured, in-depth interviews with 30 HIV-infected women (with pregnancy in prior year and 20 HIV-infected men, all reporting serodiscordant partners and accessing care in Durban, South Africa. We investigated patient-reported experiences with safer conception counseling from health care workers (HCWs. Interview transcripts were reviewed and coded using content analysis for conceptual categories and emergent themes. Results. The study findings indicate that HIV-infected patients recognize HCWs as a resource for periconception-related information and are receptive to speaking to a HCW prior to becoming pregnant, but seldom seek or receive conception advice in the clinic setting. HIV nondisclosure and unplanned pregnancy are important intervening factors. When advice is shared, patients reported receiving a range of information. Male participants showed particular interest in accessing safer conception information. Conclusions. HIV-infected men and women with serodiscordant partners are receptive to the idea of safer conception counseling. HCWs need to be supported to routinely initiate accurate safer conception counseling with HIV-infected patients of reproductive age.

  5. Pregnancy Desire, Partner Serodiscordance, and Partner HIV Disclosure among Reproductive Age HIV-Infected Women in an Urban Clinic.

    Science.gov (United States)

    Rhodes, Corinne M; Cu-Uvin, Susan; Rana, Aadia I

    2016-01-01

    Women comprise 25% of the US HIV epidemic, with many women of reproductive age. There is a need for providers to address the reproductive needs and desires of women with HIV given that effective antiretroviral therapy has transformed HIV into a chronic disease. This cross-sectional study shows high rates of partner serodiscordance (61%) and moderate HIV disclosure to partners (61%). Patients surveyed reported practitioners discuss condoms (94%) and contraception (71%) more often than pregnancy desire (38%). In our sample, 44% of the surveyed women intended future pregnancy, whereas women who did not intend future pregnancy cited HIV/health and serodiscordance as the most common reasons (56% and 35%, resp.). There was no difference in the knowledge of mother-to-child transmission risk between women who intended or did not intend future pregnancy (p = 0.71). These results underline the need for provider training in reproductive counseling to promote risk reduction and education.

  6. Evaluation of Different Parameters of Humoral and Cellular Immune Responses in HIV Serodiscordant Heterosexual Couples: Humoral Response Potentially Implicated in Modulating Transmission Rates

    Directory of Open Access Journals (Sweden)

    María Julia Ruiz

    2017-12-01

    Full Text Available As the HIV/AIDS pandemic still progresses, understanding the mechanisms governing viral transmission as well as protection from HIV acquisition is fundamental. In this context, cohorts of HIV serodiscordant heterosexual couples (SDC represent a unique tool. The present study was aimed to evaluate specific parameters of innate, cellular and humoral immune responses in SDC. Specifically, plasma levels of cytokines and chemokines, HIV-specific T-cell responses, gp120-specific IgG and IgA antibodies, and HIV-specific antibody-dependent cellular cytotoxicity (ADCC activity were assessed in nine HIV-exposed seronegative individuals (ESN and their corresponding HIV seropositive partners (HIV+-P, in eighteen chronically infected HIV subjects (C, nine chronically infected subjects known to be HIV transmitters (CT and ten healthy HIV− donors (HD. Very low magnitude HIV-specific cellular responses were found in two out of six ESN. Interestingly, HIV+-P had the highest ADCC magnitude, the lowest IgA levels and the highest IgG/IgA ratio, all compared to CT. Positive correlations between CD4+ T-cell counts and both IgG/IgA ratios and %ADCC killing uniquely distinguished HIV+-P. Additionally, evidence of IgA interference with ADCC responses from HIV+-P and CT is provided. These data suggest for the first time a potential role of ADCC and/or gp120-specific IgG/IgA balance in modulating heterosexual transmission. In sum, this study provides key information to understand the host factors that influence viral transmission, which should be considered in both the development of prophylactic vaccines and novel immunotherapies for HIV-1 infection.

  7. "I never thought that it would happen … " Experiences of HIV seroconverters among HIV-discordant partnerships in a prospective HIV prevention study in Kenya.

    Science.gov (United States)

    Ngure, Kenneth; Vusha, Sophie; Mugo, Nelly; Emmanuel-Fabula, Mira; Ngutu, Mariah; Celum, Connie; Baeten, Jared M; Heffron, Renee

    2016-12-01

    In spite of access to behavioral and biomedical HIV prevention strategies, HIV transmission occurs. For HIV-serodiscordant couples, prevention programs can be tailored to address individual and couples' needs to preserve their relationship while minimizing HIV risk. Programs for serodiscordant couples may benefit from learning from experiences of couples who transmit HIV. We conducted 20 individual in-depth interviews with 10 initially HIV-serodiscordant couples who transmitted HIV during prospective follow-up at a peri-urban research site in Thika, Kenya. Data were analyzed inductively to identify situations that led to prevention failure and coping mechanisms. Inconsistent condom use driven by low HIV risk perception and alcohol use often preceded seroconversion while persistent blame frequently hindered couples' communication soon after seroconversion. In this emerging era of antiretroviral-based HIV prevention, couples' counseling can capitalize on opportunities to foster a supportive environment to discuss initiation and adherence to time-limited pre-exposure prophylaxis and lifelong antiretroviral therapy, in addition to strategies to reduce alcohol use, diffuse blame, and use condoms.

  8. Sexual risk behaviors and acceptability of HIV pre-exposure prophylaxis among HIV-negative gay and bisexual men in serodiscordant relationships: a mixed methods study.

    Science.gov (United States)

    Brooks, Ronald A; Landovitz, Raphael J; Kaplan, Rachel L; Lieber, Eli; Lee, Sung-Jae; Barkley, Thomas W

    2012-02-01

    The objective of this mixed methods study was to examine current sexual risk behaviors, acceptability and potential adoption of pre-exposure prophylaxis (PrEP) for HIV prevention, and sexual behavior intentions with PrEP adoption among HIV-negative gay and bisexual men (GBM) in HIV serodiscordant relationships. A multiracial/ethnic sample of 25 HIV-negative GBM in serodiscordant relationships completed a qualitative interview and a brief interviewer-administered survey. A modified grounded theory approach was used to identify key themes relating to acceptability and future adoption of PrEP. Participants reported engaging in sexual risk behaviors that place them at risk for HIV infection. Participants also reported a high level of acceptability for PrEP and willingness to adopt PrEP for HIV prevention. Qualitative themes explaining future PrEP adoption included: (1) the opportunity to engage in sex using a noncondom HIV prevention method, (2) protection from HIV infection, and (3) less anxiety when engaging in sex with an HIV-positive partner. Associated with the future adoption of PrEP, a majority (64%) of participants indicated the likelihood for an increase in sexual risk behaviors and a majority (60%) of participants also indicated the likelihood for a decrease or abandonment of condom use, both of which are in contrast to the findings from the large iPrEx study. These findings suggest that the use of PrEP by HIV-negative GBM in serodiscordant relationships carries with it the potential for risk compensation. The findings suggest that PrEP only be offered as part of a comprehensive HIV prevention strategy that includes ongoing risk reduction counseling in the delivery of PrEP to help moderate risk compensation.

  9. Sexual violence and associated factors among women in HIV discordant and concordant relationships in Uganda.

    Science.gov (United States)

    Shuaib, Faisal M B; Ehiri, John E; Jolly, Pauline; Zhang, Qionghui; Emusu, Donath; Ngu, Julius; Foushee, Herman; Katongole, Drake; Kirby, Russell; Wabwire-Mangen, Fred

    2012-01-01

    HIV serodiscordance is a sexual partnership in which one partner is infected with HIV while the other is not. Managing emotional and sexual intimacy in HIV serodiscordant unions can be difficult due to concerns about HIV transmission and the challenge of initiating and maintaining safe sex. In situations where couples are jointly aware of their HIV status, women in serodiscordant unions may face increased risk of partner violence. We conducted an investigation to assess risk factors for HIV serodiscordance and determine if HIV serodiscordance is associated with incident sexual violence among a cohort of women attending HIV post-test club services at three AIDS Information Centers (AICs) in Uganda. Using a prospective study of 250 women, we elicited information about sexual violence using structured face-to-face interviews. Sexual violence and risk factors were assessed and compared among HIV positive women in HIV discordant unions, HIV negative women in discordant unions, and HIV negative women in negative concordant unions. Multivariable logistic regression was used to assess the association between participants' serostatus and sexual violence. HIV negative women in serodiscordant relationships (36.1±11.1 years, range: 19-65 years) were significantly older than either HIV positive women in serodiscordant relationships (32.2±9.0 years, range: 18-56 years), or HIV negative women in concordant relationships (32.3±11.0 years, range: 18-62), (p=0.033). Early age at sexual debut was associated with a 2.4-fold increased risk of experiencing sexual violence (OR 2.4, 95% CI 1.27-4.65). Based on unadjusted analysis, HIV positive women in discordant relationship were at highest risk for sexual violence compared to HIV negative women in discordant unions, and HIV negative women in negative concordant unions. HIV negative women in discordant relationships and those in concordant negative relationships showed no increased risk for sexual violence. However, couples' HIV

  10. HIV-1 transmission within marriage in rural Uganda: a longitudinal study.

    Directory of Open Access Journals (Sweden)

    Samuel Biraro

    Full Text Available BACKGROUND: Early initiation of antiretroviral therapy reduces risk of transmission to the uninfected partner in HIV discordant couples, but there are relatively little observational data on HIV transmission within couples from non-trial settings. The aims of this paper are to estimate HIV incidence among HIV discordant couples using longstanding observational data from a rural Ugandan population and to identify factors associated with HIV transmission within couples, including the role of HSV-2 infection. METHODS: Using existing data collected at population-wide annual serological and behavioural surveys in a rural district in southwest Uganda between 1989 and 2007, HIV discordant partners were identified. Stored serum samples were tested for HSV-2 serostatus using the Kalon ELISA test. HIV seroconversion rates and factors association with HIV seroconversion were analysed using Poisson regression. RESULTS: HIV status of both partners was known in 2465 couples and of these 259 (10.5% were HIV serodiscordant. At enrollment, HSV-2 prevalence was 87.3% in HIV positive partners and 71.5% in HIV negative partners. Of the 259 discordant couples, 62 converted to HIV (seroconversion rate 7.11/100 PYAR, 95%CI; 5.54, 9.11 with the rate decreasing from 10.89 in 1990-1994 to 4.32 in 2005-2007. Factors independently associated with HIV seroconversion were female sex, non-Muslim religion, greater age difference (man older than woman by more than 15 years, higher viral load in the positive partner and earlier calendar period. HSV-2 was not independently associated with HIV acquisition (HR 1.62, 95%CI; 0.57, 4.55 or transmission (HR 0.61, 95%CI; 0.24, 1.57. No transmissions occurred in the 29 couples where the index partner was on ART during follow up (872 person-years on ART. DISCUSSION: HIV negative partners in serodiscordant couples have a high incidence of HIV if the index partner is not on antiretroviral therapy and should be provided with interventions

  11. Community-based implementation and effectiveness in a randomized trial of a risk reduction intervention for HIV-serodiscordant couples: study protocol.

    Science.gov (United States)

    Hamilton, Alison B; Mittman, Brian S; Williams, John K; Liu, Honghu H; Eccles, Alicia M; Hutchinson, Craig S; Wyatt, Gail E

    2014-06-20

    The HIV/AIDS epidemic continues to disproportionately affect African American communities in the US, particularly those located in urban areas. Despite the fact that HIV is often transmitted from one sexual partner to another, most HIV prevention interventions have focused only on individuals, rather than couples. This five-year study investigates community-based implementation, effectiveness, and sustainability of 'Eban II,' an evidence-based risk reduction intervention for African-American heterosexual, serodiscordant couples. This hybrid implementation/effectiveness implementation study is guided by organizational change theory as conceptualized in the Texas Christian University Program Change Model (PCM), a model of phased organizational change from exposure to adoption, implementation, and sustainability. The primary implementation aims are to assist 10 community-based organizations (CBOs) to implement and sustain Eban II; specifically, to partner with CBOs to expose providers to the intervention; facilitate its adoption, implementation and sustainment; and to evaluate processes and determinants of implementation, effectiveness, fidelity, and sustainment. The primary effectiveness aim is to evaluate the effect of Eban II on participant (n = 200 couples) outcomes, specifically incidents of protected sex and proportion of condom use. We will also determine the cost-effectiveness of implementation, as measured by implementation costs and potential cost savings. A mixed methods evaluation will examine implementation at the agency level; staff members from the CBOs will complete baseline measures of organizational context and climate, while key stakeholders will be interviewed periodically throughout implementation. Effectiveness of Eban II will be assessed using a randomized delayed enrollment (waitlist) control design to evaluate the impact of treatment on outcomes at posttest and three-month follow-up. Multi-level hierarchical modeling with a multi

  12. a reflection on the impact of HIV discordance on child HIV infection

    African Journals Online (AJOL)

    cqq1a

    2010-05-09

    May 9, 2010 ... discordant couples with an HIV positive man is almost the same as that of discordant couples with an HIV positive woman [1]. There is a need to better analyze the impact of HIV sero-discordance in the context of pregnancy and prevention of mother to child transmission (PMTCT). In general, PMTCT ...

  13. Viral linkage in HIV-1 seroconverters and their partners in an HIV-1 prevention clinical trial.

    Directory of Open Access Journals (Sweden)

    Mary S Campbell

    2011-03-01

    Full Text Available Characterization of viruses in HIV-1 transmission pairs will help identify biological determinants of infectiousness and evaluate candidate interventions to reduce transmission. Although HIV-1 sequencing is frequently used to substantiate linkage between newly HIV-1 infected individuals and their sexual partners in epidemiologic and forensic studies, viral sequencing is seldom applied in HIV-1 prevention trials. The Partners in Prevention HSV/HIV Transmission Study (ClinicalTrials.gov #NCT00194519 was a prospective randomized placebo-controlled trial that enrolled serodiscordant heterosexual couples to determine the efficacy of genital herpes suppression in reducing HIV-1 transmission; as part of the study analysis, HIV-1 sequences were examined for genetic linkage between seroconverters and their enrolled partners.We obtained partial consensus HIV-1 env and gag sequences from blood plasma for 151 transmission pairs and performed deep sequencing of env in some cases. We analyzed sequences with phylogenetic techniques and developed a Bayesian algorithm to evaluate the probability of linkage. For linkage, we required monophyletic clustering between enrolled partners' sequences and a Bayesian posterior probability of ≥ 50%. Adjudicators classified each seroconversion, finding 108 (71.5% linked, 40 (26.5% unlinked, and 3 (2.0% indeterminate transmissions, with linkage determined by consensus env sequencing in 91 (84%. Male seroconverters had a higher frequency of unlinked transmissions than female seroconverters. The likelihood of transmission from the enrolled partner was related to time on study, with increasing numbers of unlinked transmissions occurring after longer observation periods. Finally, baseline viral load was found to be significantly higher among linked transmitters.In this first use of HIV-1 sequencing to establish endpoints in a large clinical trial, more than one-fourth of transmissions were unlinked to the enrolled partner

  14. High levels of viral suppression among East African HIV-infected women and men in serodiscordant partnerships initiating antiretroviral therapy with high CD4 counts and during pregnancy.

    Science.gov (United States)

    Mujugira, Andrew; Baeten, Jared; Kidoguchi, Lara; Haberer, Jessica; Celum, Connie; Donnell, Deborah; Ngure, Kenneth; Bukusi, Elizabeth; Mugo, Nelly; Asiimwe, Stephen; Odoyo, Josephine; Tindimwebwa, Edna; Bulya, Nulu; Katabira, Elly; Heffron, Renee

    2017-09-13

    People who are asymptomatic and feel healthy, including pregnant women, may be less motivated to initiate ART or achieve high adherence. We assessed whether ART initiation, and viral suppression 6, 12 and 24-months after ART initiation, were lower in HIV-infected members of serodiscordant couples who initiated during pregnancy or with higher CD4 counts. We used data from the Partners Demonstration Project, an open-label study of the delivery of integrated PrEP and ART (at any CD4 count) for HIV prevention among high-risk HIV serodiscordant couples in Kenya and Uganda. Differences in viral suppression (HIV RNA 500 cells/mm3) and during pregnancy were estimated using Poisson regression. Of 865 HIV-infected participants retained after becoming eligible for ART during study follow-up, 95% initiated ART. Viral suppression 24-months after ART initiation was high overall (97%), and comparable among those initiating ART at CD4 counts >500, 351-500 and ≤350 cells/mm3 (96% vs 97% vs 97%; relative risk [RR] 0.98; 95% CI: 0.93-1.03 for CD4 >500 vs <350 and RR 0.99; 95% CI: (0.93-1.06) for CD4 351-500 vs ≤350). Viral suppression was as likely among women initiating ART primarily to prevent perinatal transmission as ART initiation for other reasons (p=0.9 at 6 months and p=0.5 at 12 months). Nearly all HIV-infected partners initiating ART were virally suppressed by 24 months, irrespective of CD4 count or pregnancy status. These findings suggest that people initiating ART at high CD4 counts or due to pregnancy can adhere to ART as well as those starting treatment with symptomatic HIV disease or low CD4 counts.

  15. HCV Transmission between serodiscordant couples through sexual route

    International Nuclear Information System (INIS)

    Khan, R.S.A.; Khalid, S.R.; Naseer, M.; Mirza, R.

    2014-01-01

    To determine the rate of transmission of HCV between n spouses through sexual route. Study Design: Descriptive study. Place and Duration of Study: This study was carried out at Military Hospital, Rawalpindi, Pakistan. It was conducted over a period of 4 years from June 2009 to June 2013. Patients and Methods: One hundred and sixty eight consecutive patients confirmed to have HCV infection by PCR for HCV RNA were enrolled in the study. Their spouses were also included in the study, and it was established through PCR for HCV RNA that the spouses were not suffering from HCV infection. All couples were inducted in the study within the first two months of starting the study. Therefore, the maximum and minimum follow-up time was 48 months and 46 months, respectively. The spouses were questioned for HCV risk factors and were tested for HCV antibodies six monthly. Once spouses were found to be anti-HCV positive, their HCV status was confirmed with PCR for HCV RNA. Results: Out of 168 patients, 90 (53.57%) were males and 78 (46.43%) were females. PCR for HCV RNA was found to be positive in 4 of 168 (2.38%) spouses. All the se 4 couples in whom HCV transmission was found had genotype 3a. Out of the 4 spouses who tested positive for HCV RNA PCR, 3 (75%) were females and 1 (25%) was male. So HCV infection was transmitted in 3 out of 90 (3.33 %) and 1 out of 78 (1.28%) female and male spouses, respectively. In PCR for HCV RNA positive and negative spouses, the duration of marriage was 202 +- 53 and 199 +- 49 weeks; and the number of total sexual intercourses was 171 +- 93 and 169 +- 89, respectively. Conclusion: HCV transmission among serodiscordant couples in our setup did occur. The overall rate of transmission was 2.38%. The rate of transmission from male to female (3.33%) was higher than female to male (1.28%). However, a large scale study conducted over a longer duration of time is needed to recommend protected sex in serodiscordant couples if either partner is suffering

  16. Pre-exposure prophylaxis for HIV-negative persons with partners living with HIV: uptake, use, and effectiveness in an open-label demonstration project in East Africa.

    Science.gov (United States)

    Heffron, Renee; Ngure, Kenneth; Odoyo, Josephine; Bulya, Nulu; Tindimwebwa, Edna; Hong, Ting; Kidoguchi, Lara; Donnell, Deborah; Mugo, Nelly R; Bukusi, Elizabeth A; Katabira, Elly; Asiimwe, Stephen; Morton, Jennifer; Morrison, Susan; Haugen, Harald; Mujugira, Andrew; Haberer, Jessica E; Ware, Norma C; Wyatt, Monique A; Marzinke, Mark A; Frenkel, Lisa M; Celum, Connie; Baeten, Jared M

    2017-11-06

    Introduction : Pre-exposure prophylaxis (PrEP) can provide high protection against HIV infection and is a recommended intervention for HIV-negative persons with substantial HIV risk, such as individuals with a partner living with HIV.  Demonstration projects of PrEP have been conducted in diverse settings worldwide to illustrate practical examples of how PrEP can be delivered.  Methods : We evaluated delivery of PrEP for HIV-negative partners within heterosexual HIV serodiscordant couples in an open-label demonstration project in East Africa.  The delivery model integrated PrEP into HIV treatment services, prioritizing PrEP for HIV-negative partners within serodiscordant couples prior to and during the first 6 months after the partner living with HIV initiated antiretroviral therapy (ART).  We measured adherence to PrEP through medication event monitoring system (MEMS) bottle caps and quantification of tenofovir in plasma among a random sample of participants. We estimated HIV infections prevented using a counterfactual cohort simulated from the placebo arm of a previous PrEP clinical trial. Results : We enrolled 1,010 HIV serodiscordant couples that were naïve to ART and PrEP.  Ninety-seven percent (97%) of HIV-negative partners initiated PrEP, and when PrEP was dispensed, objective measures suggest high adherence: 71% of HIV-negative participants took ≥80% of expected doses, as recorded via MEMS, and 81% of plasma samples had tenofovir detected.  A total of 4 incident HIV infections were observed (incidence rate=0.24 per 100 person-years), a 95% reduction (95% CI 86-98%, pproject for African HIV-negative individuals whose partners were known to be living with HIV.  Delivery of PrEP to HIV-negative partners within HIV serodiscordant couples was feasible and should be prioritized for wide-scale implementation.

  17. Antiretroviral Therapy Reduces HIV Transmission in Discordant Couples in Rural Yunnan, China

    Science.gov (United States)

    He, Na; Duan, Song; Ding, Yingying; Rou, Keming; McGoogan, Jennifer M.; Jia, Manhong; Yang, Yuecheng; Wang, Jibao; Montaner, Julio S. G.; Wu, Zunyou

    2013-01-01

    Background Although HIV treatment as prevention (TasP) via early antiretroviral therapy (ART) has proven to reduce transmissions among HIV-serodiscordant couples, its full implementation in developing countries remains a challenge. In this study, we determine whether China's current HIV treatment program prevents new HIV infections among discordant couples in rural China. Methods A prospective, longitudinal cohort study was conducted from June 2009 to March 2011, in rural Yunnan. A total of 1,618 HIV-discordant couples were eligible, 1,101 were enrolled, and 813 were followed for an average of 1.4 person-years (PY). Routine ART was prescribed to HIV-positive spouses according to eligibility (CD4HIV incidence. Results A total of 17 seroconversions were documented within 1,127 PY of follow-up, for an overall incidence of 1.5 per 100 PY. Epidemiological and genetic evidence confirmed that all 17 seroconverters were infected via marital secondary sexual transmission. Having an ART-experienced HIV-positive partner was associated with a lower rate of seroconvertion compared with having an ART-naïve HIV-positive partner (0.8 per 100 PY vs. 2.4 per 100 PY, HR = 0.34, 95%CI = 0.12–0.97, p = 0.0436). While we found that ART successfully suppressed plasma viral load to HIV incidence among discordant couples in our sample, demonstrating the effectiveness of China's HIV treatment program at preventing new infections, and providing support for earlier ART initiation and TasP implementation in this region. PMID:24236010

  18. The role of family planning in achieving safe pregnancy for serodiscordant couples: commentary from the United States government's interagency task force on family planning and HIV service integration.

    Science.gov (United States)

    Mason, Jennifer; Medley, Amy; Yeiser, Sarah; Nightingale, Vienna R; Mani, Nithya; Sripipatana, Tabitha; Abutu, Andrew; Johnston, Beverly; Watts, D Heather

    2017-03-08

    People living with HIV (PLHIV) have the right to exercise voluntary choices about their health, including their reproductive health. This commentary discusses the integral role that family planning (FP) plays in helping PLHIV, including those in serodiscordant relationships, achieve conception safely. The United States (US) President's Emergency Plan for AIDS Relief (PEPFAR) is committed to meeting the reproductive health needs of PLHIV by improving their access to voluntary FP counselling and services, including prevention of unintended pregnancy and counselling for safer conception. Inclusion of preconception care and counselling (PCC) as part of routine HIV services is critical to preventing unintended pregnancies and perinatal infections among PLHIV. PLHIV not desiring a current pregnancy should be provided with information and counselling on all available FP methods and then either given the method onsite or through a facilitated referral process. PLHIV, who desire children should be offered risk reduction counselling, support for HIV status disclosure and partner testing, information on safer conception options to reduce the risk of HIV transmission to the partner and the importance of adhering to antiretroviral treatment during pregnancy and breastfeeding to reduce the risk of vertical transmission to the infant. Integration of PCC, HIV and FP services at the same location is recommended to improve access to these services for PLHIV. Other considerations to be addressed include the social and structural context, the health system capacity to offer these services, and stigma and discrimination of providers. Evaluation of innovative service delivery models for delivering PCC services is needed, including provision in community-based settings. The US Government will continue to partner with local organizations, Ministries of Health, the private sector, civil society, multilateral and bilateral donors, and other key stakeholders to strengthen both the policy and

  19. Knowledge and perceptions of couples' voluntary counseling and testing in urban Rwanda and Zambia: a cross-sectional household survey.

    Directory of Open Access Journals (Sweden)

    April L Kelley

    2011-05-01

    Full Text Available Most incident HIV infections in sub-Saharan Africa occur between cohabiting, discordant, heterosexual couples. Though couples' voluntary HIV counseling and testing (CVCT is an effective, well-studied intervention in Africa, <1% of couples have been jointly tested.We conducted cross-sectional household surveys in Kigali, Rwanda (n = 600 and Lusaka, Zambia (n = 603 to ascertain knowledge, perceptions, and barriers to use of CVCT.Compared to Lusaka, Kigali respondents were significantly more aware of HIV testing sites (79% vs. 56%; had greater knowledge of HIV serodiscordance between couples (83% vs. 43%; believed CVCT is good (96% vs. 72%; and were willing to test jointly (91% vs. 47%. Stigma, fear of partner reaction, and distance/cost/logistics were CVCT barriers.Though most respondents had positive attitudes toward CVCT, the majority were unaware that serodiscordance between cohabiting couples is possible. Future messages should target gaps in knowledge about serodiscordance, provide logistical information about CVCT services, and aim to reduce stigma and fear.

  20. The role of family planning in achieving safe pregnancy for serodiscordant couples: commentary from the United States government’s interagency task force on family planning and HIV service integration

    Science.gov (United States)

    Mason, Jennifer; Medley, Amy; Yeiser, Sarah; Nightingale, Vienna R.; Mani, Nithya; Sripipatana, Tabitha; Abutu, Andrew; Johnston, Beverly; Watts, D. Heather

    2017-01-01

    Abstract Introduction: People living with HIV (PLHIV) have the right to exercise voluntary choices about their health, including their reproductive health. This commentary discusses the integral role that family planning (FP) plays in helping PLHIV, including those in serodiscordant relationships, achieve conception safely. The United States (US) President’s Emergency Plan for AIDS Relief (PEPFAR) is committed to meeting the reproductive health needs of PLHIV by improving their access to voluntary FP counselling and services, including prevention of unintended pregnancy and counselling for safer conception. Discussion: Inclusion of preconception care and counselling (PCC) as part of routine HIV services is critical to preventing unintended pregnancies and perinatal infections among PLHIV. PLHIV not desiring a current pregnancy should be provided with information and counselling on all available FP methods and then either given the method onsite or through a facilitated referral process. PLHIV, who desire children should be offered risk reduction counselling, support for HIV status disclosure and partner testing, information on safer conception options to reduce the risk of HIV transmission to the partner and the importance of adhering to antiretroviral treatment during pregnancy and breastfeeding to reduce the risk of vertical transmission to the infant. Integration of PCC, HIV and FP services at the same location is recommended to improve access to these services for PLHIV. Other considerations to be addressed include the social and structural context, the health system capacity to offer these services, and stigma and discrimination of providers. Conclusion: Evaluation of innovative service delivery models for delivering PCC services is needed, including provision in community-based settings. The US Government will continue to partner with local organizations, Ministries of Health, the private sector, civil society, multilateral and bilateral donors, and other

  1. Cross-sectional study on the prevalence and predictors of pregnancy among women living in HIV discordant relationships in a rural Rakai cohort, Uganda.

    Science.gov (United States)

    Nakiganda, Lydia Jacenta; Agardh, Anette; Asamoah, Benedict Oppong

    2018-04-24

    This study examines the prevalence of pregnancy in serodiscordant couples and identifies predictors associated with pregnancy in rural Rakai, Uganda. A population-based cross-sectional study that used data from the Rakai Community Cohort Study (RCCS). We used data from the RCCS survey round 17 (2015-2016), which included 488 women in serodiscordant relationships. This study was conducted in Rakai district, located in south-western Uganda. Pregnancy status. Multivariable modified Poisson regression using stepwise selection was used to determine characteristics and behaviours associated with pregnancy status. The prevalence of pregnancy was 12% in women among serodiscordant couples. HIV-negative women in serodiscordant couples had a slightly higher pregnancy prevalence rate (13.6%) compared with HIV-positive women in serodiscordant couples (11%). Factors significantly associated with higher prevalence of pregnancy were; younger age 15-24 years (prevalence risk ratio (PRR)=4.04; 95% CI 1.72 to 9.50), middle age 25-34 years (PRR=2.49; 95% CI 1.05 to 5.89), Christian religion (PRR=2.26; 95% CI 1.41 to 3.63) and inconsistent condom use in the last 12 months (PRR=4.38, 95% CI 1.09 to 17.53). Neither HIV status nor HIV status disclosure was significantly associated with risk of getting pregnant. Nearly 12% of women in serodiscordant relationships were pregnant, highlighting the need for integrated services to prevent unintended pregnancies and reduce conceptional related risks for those choosing to conceive. Association with younger age and inconsistent condom use suggests a role for early and continued couple-based conception counselling. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  2. Couple perspectives on unintended pregnancy in an area with high HIV prevalence: A qualitative analysis in Rakai, Uganda.

    Science.gov (United States)

    Grilo, Stephanie A; Catallozzi, Marina; Heck, Craig J; Mathur, Sanyukta; Nakyanjo, Neema; Santelli, John S

    2018-03-14

    Understanding how couples perceive a recent unintended pregnancy in the context of HIV infection and high levels of gender inequality may provide insights for prevention of undesired pregnancy. We used data from 24 in-depth interviews with 8 HIV-serodiscordant and 4 seroconcordant couples living in rural Uganda and interviewed separately; between 15 and 49 years and one or both identified the pregnancy as unintended. A dyadic analysis was performed to understand each partner's perspectives on experiences of a specific pregnancy. We used the social-ecological model to guide the analysis. Issues of agency were commonly invoked in describing pregnancy. Women often cited factors that demonstrated a lack of control when making decisions about continuing the pregnancy. Men often expressed a lack of agency or control over preventing their female partner from becoming pregnant. There was much disagreement between partners about intentions regarding the specific pregnancy. Likewise, lack of communication about child spacing and pregnancy intentions was common among couples. HIV serostatus played a role in some discussions of pregnancy intention among serodiscordant couples. This qualitative analysis supports prior quantitative research on the complexity of pregnancy intentions. A lack of agency at the individual level was compounded by a lack of communication between partners.

  3. [Status of marriage and HIV transmission between couples in newly reported HIV cases before diagnosis was made, among men who have sex with men in China, 2014].

    Science.gov (United States)

    Li, J; Han, J; Xu, J; Tang, H L; Mao, Y R

    2017-06-10

    Objective: To analyze the status of marriage and HIV transmission between couples in newly reported HIV cases before diagnoses were made, among men who have sex with men (MSM) in China. Methods: Baseline and follow-up information related to newly reported cases in 2014 were collected from the Chinese HIV/AIDS Comprehensive Response Information Management System. Infected MSM who were older than 22 years of age were included in this study. HIV cases were divided into sero-concordant or sero-discordant group, according to the HIV status of the couple who were tested 180 days post-diagnosis. Multivariate logistic regression method was used to analyze the potential factors associated with HIV transmission between couples before diagnosis was made. Results: A total of 5 081 (22.7 % ) of the HIV infected MSM who had couples, were included in this study. A total of 3 715 cases had their couples tested 180 days after the diagnosis was made. 7.6 % (282) had positive couples. Results from the multivariate logistic regression analysis showed that factors as: older than 60 ( OR =2.64, 95 % CI : 1.50-4.65) years of age, being minorities ( OR =1.93, 95 % CI : 1.13-3.29), having CD(4)(+)T cells less than 500 cells/μl (<200: OR =2.91, 95 %CI : 1.82-4.65; 200-349: OR =1.98, 95 %CI : 1.22-3.23; 350-500: OR =1.69, 95 %CI : 1.00-2.86), with self-reported unsafe behaviors ( OR =1.92, 95 % CI : 1.44-2.58) etc. , were more likely to transmit HIV to their couples before the diagnosis was made. Conclusion: Behavior interventions and early HIV testing should be promoted, especially among those MSM who had couples, to avoid inter-spousal transmission.

  4. Inhibition of cornifins and up-regulation of protease inhibitors in cervicovaginal lavage imparts resistance to heterosexual HIV transmission

    Directory of Open Access Journals (Sweden)

    Sushama Rokade

    2017-12-01

    Full Text Available HIV-exposed seronegative individuals (HESNs are persons who remain seronegative despite repeated exposure to HIV, suggesting an in vivo resistance mechanism to HIV. Elucidation of endogenous factors responsible for this phenomenon may aid in the development of new classes of microbicides and therapeutics. The genital mucosal secretions of both men and women are known to contain a spectrum of antimicrobials and immune mediators that may contribute to resistance against HIV-1. Existence of HIV serodiscordant couples is a testimony to mucosal factors in the genital tract that prevent sexual transmission of the virus. We attempted to map such mucosal factors in female genital secretions of the serodiscordant couples in comparison with HIV infected and healthy participants using quantitative proteomics. The cervico vaginal lavage (CVL samples were collected from three groups of study participants (HIV infected, n=30; Un-infected Controls, n=10; Serodiscordant, n=24. Abundant proteins, albumin and globulins were removed from the pooled samples using multiple affinity removal spin cartridge (Agilent to enhance the sensitivity of iTRAQ proteomics analysis. Initial analysis identified a total of 135 proteins and associated 497 peptide matches. Serodiscordant females showed significantly down regulated levels of Cornifin A, B and C, Neutrophil gelatinase, myeloperoxidase and eosinophil peroxidase. Cornifins are cross-linked envelope protein of keratinocytes and are upregulated during inflammation. Downregulation of oxidative stress inducing enzymes and cornifins suggests immune-quiescence in serodiscordant females. CVL of these women showed significantly upregulated levels of Mucin 5B, S100A7, Alpha-2-macroglobulin, Cystatin A (protease inhibitor, Lacto-transferrin, SLPI (anti-leukoproteinase inhibitor and SERPIN G1 (protease inhibitor.  Significantly elevated levels of Cystatin B and Elafin in the CVL of serodiscordant females were confirmed by ELISA

  5. Sexually transmitted infections among HIV-1-discordant couples.

    Directory of Open Access Journals (Sweden)

    Brandon L Guthrie

    2009-12-01

    Full Text Available More new HIV-1 infections occur within stable HIV-1-discordant couples than in any other group in Africa, and sexually transmitted infections (STIs may increase transmission risk among discordant couples, accounting for a large proportion of new HIV-1 infections. Understanding correlates of STIs among discordant couples will aid in optimizing interventions to prevent HIV-1 transmission in these couples.HIV-1-discordant couples in which HIV-1-infected partners were HSV-2-seropositive were tested for syphilis, chlamydia, gonorrhea, and trichomoniasis, and HIV-1-uninfected partners were tested for HSV-2. We assessed sociodemographic, behavioral, and biological correlates of a current STI.Of 416 couples enrolled, 16% were affected by a treatable STI, and among these both partners were infected in 17% of couples. A treatable STI was found in 46 (11% females and 30 (7% males. The most prevalent infections were trichomoniasis (5.9% and syphilis (2.6%. Participants were 5.9-fold more likely to have an STI if their partner had an STI (P<0.01, and STIs were more common among those reporting any unprotected sex (OR = 2.43; P<0.01 and those with low education (OR = 3.00; P<0.01. Among HIV-1-uninfected participants with an HSV-2-seropositive partner, females were significantly more likely to be HSV-2-seropositive than males (78% versus 50%, P<0.01.Treatable STIs were common among HIV-1-discordant couples and the majority of couples affected by an STI were discordant for the STI, with relatively high HSV-2 discordance. Awareness of STI correlates and treatment of both partners may reduce HIV-1 transmission.ClinicalTrials.gov NCT00194519.

  6. From 'half-dead' to being 'free': resistance to HIV stigma, self-disclosure and support for PMTCT/HIV care among couples living with HIV in Kenya.

    Science.gov (United States)

    Spangler, Sydney A; Abuogi, Lisa L; Akama, Eliud; Bukusi, Elizabeth A; Helova, Anna; Musoke, Pamela; Nalwa, Wafula Z; Odeny, Thomas A; Onono, Maricianah; Wanga, Iris; Turan, Janet M

    2018-05-01

    In sub-Saharan Africa, self-disclosure of HIV-positive status may be a pivotal action for improving access to prevention of mother-to-child transmission services. However, understanding of HIV stigma and disclosure, and their effects on demand for care remains incomplete - particularly in the current context of new antiretroviral therapy guidelines. The purpose of this study was to explore these issues among self-disclosed couples living in southwest Kenya. We conducted 38 in-depth interviews with HIV-positive pregnant or postpartum women and their male partners. Of the 19 couples, 10 were HIV seroconcordant and 9 were serodiscordant. The textual analysis showed that HIV stigma continues to restrict full participation in community life and limit access to care by promoting fear, isolation and self-censorship. Against this backdrop, however, participants' narratives revealed varying forms and degrees of resistance to HIV stigma, which appeared to both produce and emerge from acts of self-disclosure. Such disclosure enabled participants to overcome fears and gain critical support for engaging in HIV care while further resisting HIV stigma. These findings suggest that programme interventions designed explicitly to stimulate and support processes of HIV stigma resistance and safe self-disclosure may be key to improving demand for and retention in HIV services.

  7. "Why should I take drugs for your infection?": outcomes of formative research on the use of HIV pre-exposure prophylaxis in Nigeria.

    Science.gov (United States)

    Idoko, John; Folayan, Morenike Oluwatoyin; Dadem, Nancin Yusufu; Kolawole, Grace Oluwatosin; Anenih, James; Alhassan, Emmanuel

    2015-04-10

    Nigeria has the second highest number of new HIV infections annually. Therefore, it is important to explore new strategies for preventing new infections. The introduction of pre-exposure prophylaxis (PrEP) for use by persons at high risk of HIV infection has new potential in preventing new HIV infections. The aim of this study is to explore the public opinion, community interest, and perceptions about the use and access to PrEP in Nigeria. This formative study used a mixed method approach to collect data on public opinions and perceptions on appropriate target groups for PrEP access, community interest, perceptions about the use of PrEP as an HIV-prevention tool, how best to communicate with participants about PrEP, concerns about PrEP use by serodiscordant couples, and suggestions for the design and implementation of a PrEP demonstration project. Telephone and in-depth interviews were conducted, and focus group discussions and consultative meetings were held with critical stakeholders engaged in HIV-prevention, treatment, care, and support programmes in Nigeria. An online survey was also conducted. HIV serodiscordant couples were identified as the appropriate target group for PrEP use. Most respondents felt that PrEP use by key affected populations would help reduce the HIV incidence. Stigma was identified as a major concern and a potential barrier for the acceptance and use of PrEP by HIV serodiscordant couples. Electronic and print media were identified as important means for massive public education to prevent stigma and create awareness about PrEP. In a male dominated society such as Nigeria, HIV-negative male partners in serodiscordant relationships may resist enrolment in PrEP programmes. This may be complicated by the fact that the identified index partner in most serodiscordant relationships in Nigeria is an HIV-positive woman, who is often diagnosed during pregnancy. PrEP uptake and use by HIV serodiscordant couples in Nigeria may face notable but

  8. Safety, adherence and acceptability of intermittent tenofovir/emtricitabine as HIV pre-exposure prophylaxis (PrEP among HIV-uninfected Ugandan volunteers living in HIV-serodiscordant relationships: a randomized, clinical trial.

    Directory of Open Access Journals (Sweden)

    Freddie M Kibengo

    Full Text Available BACKGROUND: Efficacy of oral pre-exposure prophylaxis (PrEP in prevention of HIV acquisition has been evaluated using a daily regimen. However, adherence to long term daily medication is rarely perfect. Intermittent regimen may be a feasible alternative. Preclinical studies have demonstrated effectiveness of intermittent PrEP in SHIV prevention among animals. However, little is known about intermittent PrEP regimens. DESIGN: Seventy two HIV-uninfected volunteers in HIV serodiscordant couple relationships in Uganda were randomly assigned to receive daily oral Tenofovir/Emtricitabine (TDF/FTC-Truvada or placebo, or intermittent (Monday, Friday and within 2 hours after sex, not to exceed one dose per day oral TDF/FTC or placebo in a 2:1:2:1 ratio. Volunteers and study staff were blinded to drug assignment, but not to regimen assignment. METHODS: Volunteers were followed for 4 months after randomization, with monthly clinical and laboratory safety assessments and comprehensive HIV risk reduction services. Adherence was monitored using medication event monitoring system (MEMS and self-report. Sexual activity data were collected via daily short text message (SMS and self-report. HIV-specific immune responses were assessed by IFN-γ ELISPOT. RESULTS: Both daily and intermittent oral TDF/FTC regimens were well tolerated. Median MEMS adherence rates were 98% (IQR: 93-100 for daily PrEP regimen, 91% (IQR: 73-97 for fixed intermittent dosing and 45% (IQR: 20-63 for post-coital dosing. SMS response rate was 74%, but increased to 80% after excluding server outages; results may have been affected by the novelty of this measure. The majority of volunteers expressed willingness with no particular preference for either regimen. CONCLUSIONS: Both daily and intermittent oral PrEP dosing regimens were safe. Adherence was high for daily and fixed intermittent dosing; post-coital dosing was associated with poor adherence. Fixed intermittent PrEP regimens may be

  9. HIV status of partners of HIV positive pregnant women in different regions of Nigeria: matters arising.

    Science.gov (United States)

    Sagay, A S; Onakewhor, J; Galadanci, H; Emuveyan, E E

    2006-12-01

    This study was conducted to determine the pattern of HIV sero-status of Partners of HIV Positive Pregnant Women in three different regions of Nigeria and to explore the implications for HIV prevention interventions. The Site Coordinators of PMTCT programs in three Nigerian cities obtained data of the HIV status of the partners of HIV positive pregnant women. The selection of Benin City, Jos and Kano was made after consideration of their ethnic, religious and cultural representation of Nigeria. Benin City represents a traditional southern Nigeria city, Kano a traditional northern city and Jos, a middle-belt, ethnically diverse cosmopolitan setting. The data were analyzed using frequencies. A total of 500 partners of HIV infected pregnant women were tested for HIV using Determine Abbott test kits. Positive results were confirmed using Western blot or a second rapid test kit. The city-by-city results showed that in Benin City (Southern Nigeria), 78.8% (104/132) of the partners were HIV negative (sero-discordant), Jos (Middle-Belt) had 48.4% (103/213) sero-discordance while Kano (Northern Nigeria) recorded a sero-discordance rate of only 7.7% (12/155). These results indicate that the dynamics of HIV transmission in marital settings in Nigeria are different in the various regions of the country. Socio-cultural and religious settings play a significant role in HIV transmission among couples. These findings should guide prevention interventions in order to achieve maximal impact.

  10. Sexual practices of people living with HIV in South Eastern Nigeria.

    Science.gov (United States)

    Ikechebelu, J; Mbamara, S U; Joe-Ikechebebelu, N N; Ezenwabachili, A O

    2009-12-01

    Couples could be in serodiscordant or seroconcordant sexual relationship. The seroconcordant could be seroconcrdant positive or negative in a heterosexual or homosexual or bisexual relationship. The various sexual practices include vaginal sex; anal sex fisting; oral sex fellatio, cunnilingus; masturbation mutual or exclusive and a host of others. These sexual practices outside safer sex guidelines will lead to HIV transmission among couples. The study is set to determine the sexual practices of people living with HIV (PLWHA) in Southeast Nigeria. This is an analytical epidemiological study. A total of 300 subjects were studied using interviewer administered questionnaires. Data is presented in tables and figures. Analysis was done using SPSS 11.0 statistical package. Most respondents were in heterosexual relationship (97%). The married couples in serodiscordant relationship were 25.3% while the singles in serodiscordant relationship were 20%. About 56% do not use condom for the adopted sexual practice although 65% believe that condom use would protect against HIV transmission. Couples in seroconcordant seronegative relationship have it as a challenge to remain so. This study suggests that the PLWHA are very important in the spread of HIV infection as they are still sexually active, in non-cohabiting conjugal unstable relationship, and they do not use the condom consistently. There is an urgent need to target this population with effective behavioural change communications that will translate to safer sexual behaviour. The practice of safer sex should be taught in every health care center, in schools and in village gatherings by qualified health care workers. This will help curb the transmission of HIV.

  11. Increased Risk of Female HIV-1 Acquisition Throughout Pregnancy and Postpartum: A Prospective Per-coital Act Analysis Among Women with HIV-1 Infected Partners.

    Science.gov (United States)

    Thomson, Kerry A; Hughes, James; Baeten, Jared M; John-Stewart, Grace; Celum, Connie; Cohen, Craig R; Ngure, Kenneth; Kiarie, James; Mugo, Nelly; Heffron, Renee

    2018-03-05

    Understanding the absolute and relative risk of HIV-1 acquisition during pregnancy and postpartum can inform HIV-1 prevention strategies for women. We used a complementary log-log model and data from 2,751 HIV-1 serodiscordant couples to compare the probability of women's HIV-1 acquisition risk per sex act during early pregnancy, late pregnancy, postpartum, and non-pregnant periods. At total of 686 pregnancies were identified and 82 incident HIV-1 infections occurred. After adjustment for condom use, age, PrEP use, and HIV-1 viral load, the per act probability of HIV-1 acquisition was higher in late pregnancy (aRR 2.82, p=0.01) and postpartum (aRR 3.97, p=0.01) compared to non-pregnant periods. The HIV-1 acquisition probability per condomless sex act for a 25 year old woman not taking PrEP with an HIV-1 infected male partner with viral load of 10,000 copies/ml was 0.0011 (95% CI: 0.005, 0.0019), 0.0022 (95% CI: 0.0004, 0.0093), 0.0030 (95% CI: 0.0007, 0.0108), and 0.0042 (95% CI: 0.0007, 0.0177) in the non-pregnant, early pregnant, late pregnant, and postpartum periods, respectively. The HIV-1 acquisition probability per condomless sex act steadily increased through pregnancy and was highest during the postpartum period, suggesting that biological changes during pregnancy and postpartum increase female HIV-1 susceptibility.

  12. 'We keep her status to ourselves': experiences of stigma and discrimination among HIV-discordant couples in South Africa, Tanzania and Ukraine.

    Science.gov (United States)

    Rispel, Laetitia C; Cloete, Allanise; Metcalf, Carol A

    2015-01-01

    In HIV-discordant relationships, the HIV-negative partner also carries the burden of a stigmatised disease. For this reason, couples often hide their HIV-discordant status from family, friends and community members. This perpetuates the silence around HIV-discordant relationships and impacts on targeted HIV prevention, treatment and counselling efforts. This article reports on experiences of stigma and discrimination among HIV-discordant couples in South Africa, Tanzania and Ukraine. During 2008, HIV-discordant couples who had been in a relationship for at least one year were recruited purposively through health-care providers and civil society organisations in the three countries. Participants completed a brief self-administered questionnaire, while semi-structured interviews were conducted with each partner separately and with both partners together. Interviews were analysed using thematic content analysis. Fifty-one couples were recruited: 26 from South Africa, 10 from Tanzania, and 15 from Ukraine. Although most participants had disclosed their HIV status to someone other than their partner, few were living openly with HIV discordance. Experiences of stigma were common and included being subjected to gossip, rumours and name-calling, and HIV-negative partners being labelled as HIV-positive. Perpetrators of discrimination included family members and health workers. Stigma and discrimination present unique and complex challenges to couples in HIV sero-discordant relationships in these three diverse countries. Addressing stigmatisation of HIV-discordant couples requires a holistic human rights approach and specific programme efforts to address discrimination in the health system.

  13. Women autonomy and aids: motivations for pregnancy in a HIV serodiscordant woman

    Directory of Open Access Journals (Sweden)

    Elen Soraia de Menezes Cabral

    2012-04-01

    Full Text Available Few studies discuss, through participation and advocacy of HIV-positive individuals, situations involving conflict about their reproductive rights and the work of health care teams. This study aimed at understanding the motivations that led a serodiscordant woman to choose pregnancy, even being aware of the risks to mother and fetus. It’s a qualitative study, adopting the case study as a methodological strategy. The historical and dialectical materialism served as theoretical framework for the analysis. The discussions were based on the model of principlist bioethics. Reflections on autonomy point to a conflicting issue between individual rights and risks for the future baby; gender and power; feminine submission and dependence, and social stigma about the disease still prevails. We concluded that professionals should be based on actual historical and social conditions, providing autonomy and recognizing rights and cultural values of those involved.

  14. Incident HSV-2 Infections Are Common Among HIV-1-discordant Couples

    Science.gov (United States)

    Muiru, Anthony N.; Guthrie, Brandon L.; Bosire, Rose; Merkel, Michele; Liu, Amy Y.; Choi, Robert Y.; Lohman-Payne, Barbara; Gatuguta, Ann; Mackelprang, Romel D.; Kiarie, James N.; Farquhar, Carey

    2013-01-01

    Background. The synergy between herpes simplex virus type 2 (HSV-2) and human immunodeficiency virus type 1 (HIV-1) is well known, but lack of knowledge about the epidemiology of HSV-2 acquisition in HIV-1-discordant couples hampers development of HSV-2 prevention interventions that could reduce HIV-1 transmission. Methods. HIV-1-discordant couples were enrolled in Nairobi, Kenya, and followed for up to 2 years. HSV-2 status was determined using HerpeSelect HSV-2 ELISA. Correlates of prevalence and incidence were assessed. Results. Of 469 HIV-1-discordant couples, at baseline, 353 (75.3%) were affected by HSV-2, of which 189 (53.5%) were concordantly HSV-2 seropositive and 164 (46.5%) were HSV-2-discordant. Prevalence was lowest among HIV-1-uninfected men (39.9%) compared to HIV-1-infected women (64.8%), HIV-1-infected men (66.7%), and HIV-1-uninfected women (68.5%). During follow-up, HSV-2 seroincidence was 14.9 per 100 person-years. Incidence was 1.6-fold higher among females compared to males (95% confidence interval [CI], 1.00–2.48) and 2.5-fold higher in HIV-1-infected compared to uninfected women (95% CI, 1.12–5.74). At least 30% of incident HSV-2 infections originated from an outside partner. Conclusions. The high HSV-2 prevalence and incidence in HIV-1-discordant couples in sub-Saharan Africa suggest HSV-2 treatment and prevention could be an effective targeted strategy to reduce HSV-2 and HIV-1 transmission in this high-risk population. PMID:23840044

  15. Further research needed to support a policy of antiretroviral therapy as an HIV prevention initiative

    DEFF Research Database (Denmark)

    Rodger, Alison J; Bruun, Tina; Vernazza, Pietro

    2013-01-01

    The results from the HPTN 052 trial have increased the focus on use of antiretroviral therapy (ART) for prevention of HIV transmission; however, condom use also effectively prevents HIV transmission. Studies in heterosexual serodiscordant couples with viral suppression have so far only reported f...

  16. Ambiguity, ambivalence, and apprehensions of taking HIV-1 pre-exposure prophylaxis among male couples in San Francisco: a mixed methods study.

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    Parya Saberi

    Full Text Available We conducted a mixed-methods study to examine serodiscordant and seroconcordant (HIV-positive/HIV-positive male couples' PrEP awareness, concerns regarding health care providers offering PrEP to the community, and correlates of PrEP uptake by the HIV-negative member of the couple.Qualitative sub-study included one-on-one interviews to gain a deeper understanding of participants' awareness of and experiences with PrEP and concerns regarding health care providers offering PrEP to men who have sex with men (MSM. Quantitative analyses consisted of a cross-sectional study in which participants were asked about the likelihood of PrEP uptake by the HIV-negative member of the couple and level of agreement with health care providers offering PrEP to anyone requesting it.We used multivariable regression to examine associations between PrEP questions and covariates of interest and employed an inductive approach to identify key qualitative themes.Among 328 men (164 couples, 62% had heard about PrEP, but approximately one-quarter were mistaking it with post-exposure prophylaxis. The majority of participants had low endorsement of PrEP uptake and 40% were uncertain if health care providers should offer PrEP to anyone requesting it. Qualitative interviews with 32 men suggest that this uncertainty likely stems from concerns regarding increased risk compensation. Likelihood of future PrEP uptake by the HIV-negative member of the couple was positively associated with unprotected insertive anal intercourse but negatively correlated with unprotected receptive anal intercourse.Findings suggest that those at greatest risk may not be receptive of PrEP. Those who engage in moderate risk express more interest in PrEP; however, many voice concerns of increased risk behavior in tandem with PrEP use. Results indicate a need for further education of MSM communities and the need to determine appropriate populations in which PrEP can have the highest impact.

  17. Ambiguity, ambivalence, and apprehensions of taking HIV-1 pre-exposure prophylaxis among male couples in San Francisco: a mixed methods study.

    Science.gov (United States)

    Saberi, Parya; Gamarel, Kristi E; Neilands, Torsten B; Comfort, Megan; Sheon, Nicolas; Darbes, Lynae A; Johnson, Mallory O

    2012-01-01

    We conducted a mixed-methods study to examine serodiscordant and seroconcordant (HIV-positive/HIV-positive) male couples' PrEP awareness, concerns regarding health care providers offering PrEP to the community, and correlates of PrEP uptake by the HIV-negative member of the couple. Qualitative sub-study included one-on-one interviews to gain a deeper understanding of participants' awareness of and experiences with PrEP and concerns regarding health care providers offering PrEP to men who have sex with men (MSM). Quantitative analyses consisted of a cross-sectional study in which participants were asked about the likelihood of PrEP uptake by the HIV-negative member of the couple and level of agreement with health care providers offering PrEP to anyone requesting it. We used multivariable regression to examine associations between PrEP questions and covariates of interest and employed an inductive approach to identify key qualitative themes. Among 328 men (164 couples), 62% had heard about PrEP, but approximately one-quarter were mistaking it with post-exposure prophylaxis. The majority of participants had low endorsement of PrEP uptake and 40% were uncertain if health care providers should offer PrEP to anyone requesting it. Qualitative interviews with 32 men suggest that this uncertainty likely stems from concerns regarding increased risk compensation. Likelihood of future PrEP uptake by the HIV-negative member of the couple was positively associated with unprotected insertive anal intercourse but negatively correlated with unprotected receptive anal intercourse. Findings suggest that those at greatest risk may not be receptive of PrEP. Those who engage in moderate risk express more interest in PrEP; however, many voice concerns of increased risk behavior in tandem with PrEP use. Results indicate a need for further education of MSM communities and the need to determine appropriate populations in which PrEP can have the highest impact.

  18. [Enhanced prenatal HIV couple oriented counselling session and couple communication about HIV (ANRS 12127 Prenahtest Trial)].

    Science.gov (United States)

    Plazy, M; Orne-Gliemann, J; Balestre, E; Miric, M; Darak, S; Butsashvili, M; Tchendjou, P; Dabis, F; Desgrées du Loû, A

    2013-08-01

    The Prenahtest study investigated the efficacy of a couple-oriented HIV counselling session (COC) in encouraging couple HIV counselling and testing, and improving intra-couple communication about sexual and reproductive health. We report here on the effect of COC on intra-couple communication about HIV. Within this 4-country trial (India, Georgia, Dominican Republic and Cameroon), 484 to 491 pregnant women per site were recruited and individually randomized to receive either the COC intervention, enhanced counselling with role playing, or standard post-test HIV counselling. Women were interviewed at recruitment, before HIV testing (T0), and 2 to 8 weeks after post-test HIV counselling (T1). Four dichotomous variables documented intra-couple communication about HIV at T1: 1) discussion about HIV, 2) discussion about condom use, 3) suggesting HIV testing and 4) suggesting couple HIV counselling to the partner. An intra-couple HIV communication index was created: low degree of communication ("yes" response to zero or one of the four variables), intermediate degree of communication ("yes" to two or three variables) or high degree of communication ("yes" to the four variables). To estimate the impact of COC on the intra-couple HIV communication index, multivariable logistic regressions were conducted. One thousand six hundred and seven women were included in the analysis of whom 54 (3.4%) were HIV-infected (49 in Cameroon). In the four countries, the counselling group was associated with intra-couple HIV communication (P≤0.03): women allocated to the COC group were significantly more likely to report high or intermediate degrees of intra-couple communication about HIV (versus low degree of communication) than women allocated to standard counselling. COC improved short-term communication about HIV within couples in different sociocultural contexts, a positive finding for a couple approach to HIV prevention. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  19. Convivendo com a diferença: o impacto da sorodiscordância na vida afetivo-sexual de portadores do HIV/AIDS Conviviendo con la diferencia: el impacto de la serodiscordancia en la vida afectiva-sexual de portadores del VIH/SIDA Living with the difference: the impact of serodiscordance on the affective and sexual life of HIV/AIDS patients

    Directory of Open Access Journals (Sweden)

    Renata Karina Reis

    2010-09-01

    en altera-ciones de la respuesta sexual humana y favoreciendo hasta la propia abstinencia sexual. Se pone de manifiesto la necesidad de atención por parte de equipos interdisciplinarios para los portadores de HIB/aids y también de sus parejas, a fin de proporcionarles asistencia integral, contemplando la sexualidad y las dificultades derivadas de la serodiscordancia.The purpose of this descriptive-exploratory qualitative study was to describe and analyze the impact of serodiscordance on the affective-sexual life of HIV/AIDS patients who have HIV seronegative heterosexual partners. Eleven HIV/AIDS carriers in outpatient clinic follow-up were interviewed, in a reference university-hospital in the state of São Paulo. Data were collected through recorded individual interviews and analyzed according to Prose analysis. Living with HIV/AIDS serodiscordance implies these couples have to deal with several intimacy-related difficulties, due to the possibility of HIV transmission to the seronegative partner. This has a negative effect on serodiscordant partners, reflecting in chan-ges in human sexual response, which could lead to sexual abstinence. Interdisciplinary care should be provided to HIV/AIDS carriers and their partners, thus providing comprehensive care regarding their sexuality and difficulties caused by serodiscordance.

  20. Percepções de alunas de graduação em enfermagem sobre parcerias sorodiscordantes para o HIV/AIDS Percepciones de alumnos de enfermería sobre parejas serodiscordantes para el VIH/SIDA Nursing students' perceptions on HIV serodiscordant partnerships

    Directory of Open Access Journals (Sweden)

    Hugo Fernandes

    2005-08-01

    nursing students' perceptions on mixed-HIV-status couples. Social Representation Theory was used to get to know how the students feel, think and act towards HIV/aids serodiscordance. Six fourth-year nursing students were interviewed. Participants were between 20 and 26 years old. The "Projective Thematic Drawing" and a structure interview were used for data collection. Data were analyzed by means of "Thematic Content Analysis". The obtained data revealed the students' perceptions on serodiscordant couples. This study triggered future reflections/discussions on health education for mixed-HIV-status couples and nursing care.

  1. Dificuldades enfrentadas pelos parceiros sorodiscordantes ao HIV na manutençao do sexo seguro Dificultades enfrentadas por las parejas serodiscordantes para el HIV en el mantenimiento del sexo seguro Difficulties faced by HIV mixed status couples in maintaining safe sex

    Directory of Open Access Journals (Sweden)

    Renata Karina Reis

    2005-02-01

    ón específica de los servicios de salud, y las estrategias preventivas deben contemplar los aspectos cultural y psicosocial que se constituyen en aspectos importantes de la vulnerabilidad de las parejas serodiscordantes.This study aimed to identify the factors that interfere in maintaining safe sex. Data were collected through individual interviews with 11 HIV/aids patients living with HIV-negative partners, under clinical treatment at a specialized aids clinic. Analysis was based on Prose analysis by André (1983. The concept of vulnerability was used as a theoretical reference framework. The sexual prevention of HIV/aids for the non infected partner constitutes one of the largest challenges for the serodiscordant couples, because men and women accept condoms differently. The greater motivation towards condom use among serodiscordant couples does not eliminate the difficulties to use them for maintaining safe sex. The serodiscordant couples deserve specific assistance, and the preventive strategies should contemplate the cultural and psychosocial aspects that constitute important aspects of mixed-status partner vulnerability.

  2. The Role of Relationship Dynamics and Gender Inequalities As Barriers to HIV-Serostatus Disclosure: Qualitative Study among Women and Men Living with HIV in Durban, South Africa

    Directory of Open Access Journals (Sweden)

    Divya S. Bhatia

    2017-07-01

    Full Text Available BackgroundThis qualitative study investigated gender power inequalities as they contribute to relationship dynamics and HIV-serostatus disclosure among men and women living with HIV in Durban, South Africa. HIV serodiscordance among men and women within stable partnerships contributes to high HIV incidence in southern Africa, yet disclosure rates remain low. Given the emphasis on prevention for HIV-serodiscordant couples, this research supports the urgent need to explore how best to support couples to recognize that they are part of this priority population and to access appropriate prevention and treatment.MethodsThirty-five in-depth individual interviews were conducted with 15 HIV-positive men and 20 HIV-positive women (not couples receiving care at public-sector clinics near Durban. A structured coding scheme was developed to investigate men’s and women’s attitudes toward HIV-serostatus disclosure and behaviors of sharing (or not sharing HIV serostatus with a partner. Narratives were analyzed for barriers and facilitators of disclosure through the lens of sociocultural gender inequality, focusing on reasons for non-disclosure.ResultsAmong 35 participants: median age was 33 years (men and 30 years (women; average years since HIV diagnosis was 1 (men and 1.5 (women. Four themes related to gender inequality and HIV-serostatus disclosure emerged: (1 Men and women fear disclosing to partners due to concerns about stigma and relationship dissolution, (2 suspicions and mistrust between partners underlies decisions for non-disclosure, (3 unequal, gendered power in relationships causes differential likelihood and safety of disclosure among men and women, and (4 incomplete or implicit disclosure are strategies to navigate disclosure challenges. Findings illustrate HIV-serostatus disclosure as a complex process evolving over time, rather than a one-time event.ConclusionPartner communication about HIV serostatus is infrequent and complicated

  3. Vulnerabilidade ao HIV/AIDS e a prevenção da transmissão sexual entre casais sorodiscordantes Vulnerabilidad al VIH/SIDA y la prevención de la transmisión sexual entre parejas donde solo un sujeto está contaminado por el VIH Vulnerability and prevention of sexual HIV transmission among HIV/AIDS serodiscordant couples

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    Renata Karina Reis

    2009-09-01

    influencia en la manutención del sexo seguro son factores de vulnerabilidad para el compañero sexual no contaminado. Los servicios especializados en la atención a individuos con VIH/SIDA necesitan incluir al compañero sexual en las acciones educativas/preventivas promovidas por los profesionales de la salud.This exploratory, descriptive study aimed to describe and analyze the vulnerability of HIV serodiscordant couples. The research was developed at an Aids Outpatient Service in a city in the State of Sao Paulo. Data were collected through individual interviews with 11 HIV/AIDS carriers who had a known serodiscordant partner. Prose analysis was applied for data organization and analyses, and the concept of vulnerability was used as a theoretical reference. The naturalization of HID/AIDS related to an undetectable viral load, the invulnerability feeling that stems from the time spent together by the couple, and its influence in the maintenance of safe sex are vulnerability factors for seronegative sexual partners. Specialized services to assist HIV/AIDS carriers need to include sexual partners in actions promoted by healthcare professionals targeting prevention and/or education.

  4. Obtenção de gametas seguros por meio de associação de técnicas de processamento seminal para casais sorodiscordantes para HIV Safe gametes acquisition through association of seminal processing techniques with HIV serodiscordant couples

    Directory of Open Access Journals (Sweden)

    Priscila Queiroz

    2008-04-01

    ão interferiu nos parâmetros laboratoriais de ciclos de reprodução humana assistida. Por outro lado, demonstrou excelentes resultados na obtenção de gametas seguros para casais sorodiscordantes.PURPOSE: the propose of this study was to analyze the clinical and laboratorial parameters of patients submitted to human assisted reproduction techniques with association of sperm processing techniques, in order to remove virus particles from semen samples of couples in which men was infected by human immunodeficiency virus (HIV. METHODS: it was assessed 11 intracytoplasmatic sperm injection (ICSI cycles from couples whose men were HIV seropositive (HIV Group, and 35 cycles in which semen donors' samples were used in ICSI procedures (Control Group. Semen samples from Control Group were submitted to routine semen analysis, sperm wash and cryopreservation. The man from HIV Group received previous antibiotic therapy; the semen samples were analyzed routinely and prepared by sperm wash and density gradient method before cryopreservation. Those samples were evaluated to viral load and ICSI was performed when no HIV was detected. RESULTS: regards to semen analysis the groups were similar to sperm concentration and progressive motility. Nevertheless, the percentage of sperm with normal morphology were higher on Control Group (14.3% than HIV (5.8%; p=0.002. On embryo parameters assessment, the normal fertilization (CT: 74.7% and HIV: 71.7; p=0.838, respectively and good embryos rate (CT: 42.4% and HIV: 65.1%; p=0.312, respectively were comparable. On the other hand, the Control Group presented better clinic results than HIV Group (ongoing pregnancy rate: 52.9% versus 12.5%; p=0.054, and implantation rate: 42.6 versus 10.4%; p=0.059, respectively, however the differences were not statistically significant. After delivery, no seroconversion was observed on mother and child. CONCLUSIONS: the association of sperm processing techniques in order to remove HIV from semen samples does not

  5. HIV and dyadic intervention: an interdependence and communal coping analysis.

    Directory of Open Access Journals (Sweden)

    Catherine M Montgomery

    Full Text Available The most common form of HIV transmission in sub-Saharan Africa is heterosexual sex between two partners. While most HIV prevention interventions are aimed at the individual, there is mounting evidence of the feasibility, acceptability, and efficacy of dyadic interventions. However, the mechanisms through which dyadic-level interventions achieve success remain little explored. We address this gap by using Lewis et al's interdependence model of couple communal coping and behaviour change to analyse data from partners participating in an HIV prevention trial in Uganda and Zambia.We conducted a comparative qualitative study using in-depth interviews. Thirty-three interviews were conducted in total; ten with couples and twenty-three with staff members at the two sites. The Ugandan site recruited a sero-discordant couple cohort and the Zambian site recruited women alone. Spouses' transformation of motivation is strong where couples are recruited and both partners stand to gain considerably by participating in the research; it is weaker where this is not the case. As such, coping mechanisms differ in the two sites; among sero-discordant couples in Uganda, communal coping is evidenced through joint consent to participate, regular couple counselling and workshops, sharing of HIV test results, and strong spousal support for adherence and retention. By contrast, coping at the Zambian site is predominantly left to the individual woman and occurs against a backdrop of mutual mistrust and male disenfranchisement. We discuss these findings in light of practical and ethical considerations of recruiting couples to HIV research.We argue for the need to consider the broader context within which behaviour change occurs and propose that future dyadic research be situated within the framework of the 'risk environment'.

  6. An economic evaluation of conception strategies for heterosexual serodiscordant couples where the male partner is HIV-positive.

    Science.gov (United States)

    Letchumanan, Michelle; Coyte, Peter C; Loutfy, Mona

    2015-01-01

    To conduct an economic evaluation of the three commonly used interventions that reduce sexual HIV transmission when an HIV-negative female aims to conceive with an HIV-positive male on combination antiretroviral therapy (condomless sex restricted to timed ovulation [CS], sperm washing with intrauterine insemination [SW] and condomless sex restricted to timed ovulation with pre-exposure prophylaxis [CS-PrEP]). As SW and CS-PrEP are only privately available for pregnancy planning for this population in Canada, this study was conducted to inform policy decisions concerning potential public health insurance coverage, as well as to inform fertility counselling in settings with adequate combination antiretroviral therapy access globally. We developed a cohort Markov model with a lifetime horizon and used the perspective of Ontario's Ministry of Health (MOH). Input parameters were drawn from literature, the MOH's Schedule of Benefits and a time trade-off questionnaire designed for this study. Outcome measures included quality-adjusted life-years and incremental cost-effectiveness. Costs and benefits were discounted at annual rates of 3%. Costs were reported in Canadian 2013 dollars and an exchange rate of 1 USD to 1.066 CND was applied where necessary. Sensitivity analysis assessed the uncertainty of model parameters. The base case analysis found that CS-PrEP and SW were each more costly and less effective at conception than CS. The results were robust in the sensitivity analysis and suggest that CS is the dominant conception strategy in this population. Neither CS-PrEP nor SW represent better value for money relative to CS as a conception option for HIV-discordant couples with positive male partners. Based on these findings, CS-PrEP and SW cannot be recommended for public-funding in developed countries.

  7. Barriers to Antiretroviral Initiation in HIV-1-Discordant Couples

    Science.gov (United States)

    Guthrie, Brandon L.; Choi, Robert Y.; Liu, Amy Y.; Mackelprang, Romel D.; Rositch, Anne F.; Bosire, Rose; Manyara, Lucy; Gatuguta, Anne; Kiarie, James N.; Farquhar, Carey

    2011-01-01

    BACKGROUND In Kenya and much of sub-Saharan Africa, nearly half of all couples affected by HIV are discordant. Antiretroviral therapy (ART) slows disease progression in HIV-1-infected individuals, and reduces transmission to uninfected partners. We examined time to ART initiation and factors associated with delayed initiation in HIV-1-discordant couples in Nairobi. METHODS HIV-1-discordant couples were enrolled and followed quarterly for up to 2 years. Clinical staff administered questionnaires and conducted viral loads and CD4 counts. Participants with a CD4 count meeting ART criteria were referred to a nearby PEPFAR-funded treatment center. Barriers to ART initiation among participants with a CD4 count eligible for ART were assessed by Cox regression. RESULTS Of 439 HIV-1-infected participants (63.6% females and 36.4% males) 146 met CD4 count criteria for ART during follow-up. Median time from meeting CD4 criteria until ART initiation was 8.9 months, with 42.0% of eligible participants on ART by 6 months and 63.4% on ART by 1 year. The CD4 count at the time of eligibility was inversely associated with time to ART initiation (HR=0.49, p< 0.001). Compared to homeowners, those paying higher rents started ART 48% more slowly (p=0.062) and those paying lower rents started 71% more slowly (p=0.002). CONCLUSIONS Despite access to regular health care, referrals to treatment centers, and free access to ART, over a third of participants with an eligible CD4 count had not started ART within 1 year. Factors of lower socioeconomic status may slow ART initiation and targeted approaches are needed to avoid delays in treatment initiation. PMID:21826010

  8. Beyond HIV-serodiscordance: Partnership communication dynamics that affect engagement in safer conception care.

    Directory of Open Access Journals (Sweden)

    Lynn T Matthews

    Full Text Available We explored acceptability and feasibility of safer conception methods among HIV-affected couples in Uganda.We recruited HIV-positive men and women on antiretroviral therapy (ART ('index' from the Uganda Antiretroviral Rural Treatment Outcomes cohort who reported an HIV-negative or unknown-serostatus partner ('partner', HIV-serostatus disclosure to partner, and personal or partner desire for a child within two years. We conducted in-depth interviews with 40 individuals from 20 couples, using a narrative approach with tailored images to assess acceptability of five safer conception strategies: ART for the infected partner, pre-exposure prophylaxis (PrEP for the uninfected partner, condomless sex timed to peak fertility, manual insemination, and male circumcision. Translated and transcribed data were analyzed using thematic analysis.11/20 index participants were women, median age of 32.5 years, median of 2 living children, and 80% had HIV-RNA <400 copies/mL. Awareness of HIV prevention strategies beyond condoms and abstinence was limited and precluded opportunity to explore or validly assess acceptability or feasibility of safer conception methods. Four key partnership communication challenges emerged as primary barriers to engagement in safer conception care, including: (1 HIV-serostatus disclosure: Although disclosure was an inclusion criterion, partners commonly reported not knowing the index partner's HIV status. Similarly, the partner's HIV-serostatus, as reported by the index, was frequently inaccurate. (2 Childbearing intention: Many couples had divergent childbearing intentions and made incorrect assumptions about their partner's desires. (3 HIV risk perception: Participants had disparate understandings of HIV transmission and disagreed on the acceptable level of HIV risk to meet reproductive goals. (4 Partnership commitment: Participants revealed significant discord in perceptions of partnership commitment. All four types of partnership

  9. Unsafe sex in regular partnerships among heterosexual persons living with HIV: evidence from a large representative sample of individuals attending outpatients services in France (ANRS-EN12-VESPA Study).

    Science.gov (United States)

    Bouhnik, Anne-Déborah; Préau, Marie; Lert, France; Peretti-Watel, Patrick; Schiltz, Marie-Ange; Obadia, Yolande; Spire, Bruno

    2007-01-01

    Risky sexual behaviour remains frequent among people living with HIV. We analysed factors associated with unsafe sex within serodiscordant couples among heterosexual individuals living with HIV in France. In 2003, a face-to-face survey was conducted among individuals selected in a random stratified sample of 102 French hospital departments delivering HIV care. This analysis included adults heterosexual participants in a regular partnership for at least 12 months with a seronegative/unknown serostatus partner, HIV-diagnosed for at least 12 months. Unsafe sex was defined as reporting inconsistent condom use in the prior 12 months. Among men and women, participants who reported unsafe sex were compared with those who did not. 663 heterosexual adults reported being in a serodiscordant regular partnership. Women accounted for 41% of participants and 26% of the sample were immigrants. Unsafe sex with the steady partner was reported by 26% of men and 34% of women (p=0.024). For men, factors independently associated with unsafe sex were being in a relationship for more than 10 years, being in a difficult financial situation and reporting regular consumption of alcohol to excess. Among women, having a history of drug use, not being aware of partner's serostatus, and reporting a difficult financial situation were independently associated with unsafe sex. In addition, immigrant women were associated with safer sex. A high number of serodiscordant couples continue to report risky sexual behaviour, and related factors are gender-specific. Couple-level interventions are essential in order to prevent HIV-transmission and to encourage negotiation within couples.

  10. HIV testing among male partners of pregnant women in Nigeria: a missing link in the elimination of mother-to-child transmission of HIV.

    Science.gov (United States)

    Olakunde, Babayemi O; Adeyinka, Daniel A; Oladele, Tolulope; Ozigbu, Chamberline E

    2018-03-01

    In this study, we assessed male partner testing and the serodiscordance rate among pregnant women and their partners in the prevention of mother-to-child transmission (PMTCT) programme in Nigeria. We conducted a retrospective analysis of the consolidated national health sector PMTCT data over a five-year period (2012-2016). Over the period, a total of 11,833,062 pregnant women were tested for HIV with a positivity rate of 2.2%. About 266,188 (2.2%) of sexual partners of pregnant women who presented at PMTCT clinics had an HIV test within the period. The uptake of male partner testing varied across the years, ranging from 22,269 (1.7%) in 2012 to 90,603 (2.9%) in 2014 (χ 2 for trend = 1320; p HIV-negative pregnant women who tested was higher than the proportion of partners of HIV-positive pregnant women (81% versus 19%, respectively). The serodiscordance rate among partners who tested over the five-year period was 18%. The serodiscordance rate declined from 24% in 2012 to 13% in 2016 (χ 2 for trend = 1202; p HIV combination prevention approach in the HIV response.

  11. Sexual and Reproductive Health in HIV Serodiscordant Couples

    African Journals Online (AJOL)

    AJRH Managing Editor

    counseling and testing programmes where condom use was recommended for ... and a 75% risk reduction in the TDF-FTC group, ... provide the couple and individual partners with ..... Elective caesarean-section versus vaginal delivery in.

  12. HIV-1 transmitting couples have similar viral load set-points in Rakai, Uganda.

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    T Déirdre Hollingsworth

    2010-05-01

    Full Text Available It has been hypothesized that HIV-1 viral load set-point is a surrogate measure of HIV-1 viral virulence, and that it may be subject to natural selection in the human host population. A key test of this hypothesis is whether viral load set-points are correlated between transmitting individuals and those acquiring infection. We retrospectively identified 112 heterosexual HIV-discordant couples enrolled in a cohort in Rakai, Uganda, in which HIV transmission was suspected and viral load set-point was established. In addition, sequence data was available to establish transmission by genetic linkage for 57 of these couples. Sex, age, viral subtype, index partner, and self-reported genital ulcer disease status (GUD were known. Using ANOVA, we estimated the proportion of variance in viral load set-points which was explained by the similarity within couples (the 'couple effect'. Individuals with suspected intra-couple transmission (97 couples had similar viral load set-points (p = 0.054 single factor model, p = 0.0057 adjusted and the couple effect explained 16% of variance in viral loads (23% adjusted. The analysis was repeated for a subset of 29 couples with strong genetic support for transmission. The couple effect was the major determinant of viral load set-point (p = 0.067 single factor, and p = 0.036 adjusted and the size of the effect was 27% (37% adjusted. Individuals within epidemiologically linked couples with genetic support for transmission had similar viral load set-points. The most parsimonious explanation is that this is due to shared characteristics of the transmitted virus, a finding which sheds light on both the role of viral factors in HIV-1 pathogenesis and on the evolution of the virus.

  13. Families Living with Blood-Borne Viruses: The Case for Extending the Concept of “Serodiscordance”

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    Asha Persson

    2017-01-01

    Full Text Available The concept of “serodiscordance” (mixed infection status is primarily associated with epidemiological concerns about HIV transmission risk in couples. We make the case for extending this concept to include families with mixed HIV and viral hepatitis status. Social research on couples with mixed HIV and hepatitis C status has laid an important foundation for illuminating how experiences of serodiscordance within intimate partnerships are much broader than concerns about risk. This body of work attests to serodiscordance holding promise as a valuable concept for understanding viral infections as socially situated and intensely relational phenomena. However, serodiscordance is still limited as a concept because of its near universal focus on couples. It is rarely applied to wider relationships, including family networks beyond the couple. Despite evidence in the literature that families are affected by blood-borne viruses in multiple social, emotional, financial, and generational ways, the concept of serodiscordance does not capture these broader dynamics. Making serodiscordance more inclusive is an important step in recognising the diverse ways families’ everyday lives, relationships, and futures can be entangled with HIV, hepatitis C, and hepatitis B, and for understanding how today’s era of effective treatment options might shape the “family life” of viral infections.

  14. Perspectives of healthcare providers and HIV-affected individuals and couples during the development of a Safer Conception Counseling Toolkit in Kenya: stigma, fears, and recommendations for the delivery of services.

    Science.gov (United States)

    Mmeje, Okeoma; Njoroge, Betty; Akama, Eliud; Leddy, Anna; Breitnauer, Brooke; Darbes, Lynae; Brown, Joelle

    2016-01-01

    Reproduction is important to many HIV-affected individuals and couples and healthcare providers (HCPs) are responsible for providing resources to help them safely conceive while minimizing the risk of sexual and perinatal HIV transmission. In order to fulfill their reproductive goals, HIV-affected individuals and their partners need access to information regarding safer methods of conception. The objective of this qualitative study was to develop a Safer Conception Counseling Toolkit that can be used to train HCPs and counsel HIV-affected individuals and couples in HIV care and treatment clinics in Kenya. We conducted a two-phased qualitative study among HCPs and HIV-affected individuals and couples from eight HIV care and treatment sites in Kisumu, Kenya. We conducted in-depth interviews (IDIs) and focus group discussions (FGDs) to assess the perspectives of HCPs and HIV-affected individuals and couples in order to develop and refine the content of the Toolkit. Subsequently, IDIs were conducted among HCPs who were trained using the Toolkit and FGDs among HIV-affected individuals and couples who were counseled with the Toolkit. HIV-related stigma, fears, and recommendations for delivery of safer conception counseling were assessed during the discussions. One hundred and six individuals participated in FGDs and IDIs; 29 HCPs, 49 HIV-affected women and men, and 14 HIV-serodiscordant couples. Participants indicated that a safer conception counseling and training program for HCPs is needed and that routine provision of safer conception counseling may promote maternal and child health by enhancing reproductive autonomy among HIV-affected couples. They also reported that the Toolkit may help dispel the stigma and fears associated with reproduction in HIV-affected couples, while supporting them in achieving their reproductive goals. Additional research is needed to evaluate the Safer Conception Toolkit in order to support its implementation and use in HIV care and

  15. Reassessment of HIV-1 acute phase infectivity: accounting for heterogeneity and study design with simulated cohorts.

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    Steve E Bellan

    2015-03-01

    Full Text Available The infectivity of the HIV-1 acute phase has been directly measured only once, from a retrospectively identified cohort of serodiscordant heterosexual couples in Rakai, Uganda. Analyses of this cohort underlie the widespread view that the acute phase is highly infectious, even more so than would be predicted from its elevated viral load, and that transmission occurring shortly after infection may therefore compromise interventions that rely on diagnosis and treatment, such as antiretroviral treatment as prevention (TasP. Here, we re-estimate the duration and relative infectivity of the acute phase, while accounting for several possible sources of bias in published estimates, including the retrospective cohort exclusion criteria and unmeasured heterogeneity in risk.We estimated acute phase infectivity using two approaches. First, we combined viral load trajectories and viral load-infectivity relationships to estimate infectivity trajectories over the course of infection, under the assumption that elevated acute phase infectivity is caused by elevated viral load alone. Second, we estimated the relative hazard of transmission during the acute phase versus the chronic phase (RHacute and the acute phase duration (dacute by fitting a couples transmission model to the Rakai retrospective cohort using approximate Bayesian computation. Our model fit the data well and accounted for characteristics overlooked by previous analyses, including individual heterogeneity in infectiousness and susceptibility and the retrospective cohort's exclusion of couples that were recorded as serodiscordant only once before being censored by loss to follow-up, couple dissolution, or study termination. Finally, we replicated two highly cited analyses of the Rakai data on simulated data to identify biases underlying the discrepancies between previous estimates and our own. From the Rakai data, we estimated RHacute = 5.3 (95% credibility interval [95% CrI]: 0.79-57 and dacute

  16. What is the benefit of the biomedical and behavioral interventions in preventing HIV transmission?

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    Ricardo Kuchenbecker

    2015-09-01

    Full Text Available ABSTRACTIntroduction:Scientific evidence supports the sinergy between biomedical and behavioral interventions aimed at preventing the transmission of HIV as a strategy to eradicate AIDS.Objective:To characterize comparatively the benefits from biomedical and behavioral interventions to prevent HIV transmission.Methods:Narrative review. We performed a comparative analysis of the benefits of studied interventions by means of estimating the number needed to treat (NNT. Evaluated interventions: counseling activities for behavior change to prevent exposure to HIV; antiretroviral pre-exposure prophylaxis (PrEP and antiretroviral post-exposure prophylasis (PEP for HIV and treatment of serodiscordant couples as a strategy for prevention of HIV transmission (TasP.Results:counseling interventions and TasP have smaller NNTs, equal to, respectively, 11 (95%CI 9 - 18 at 12 months and 34 (95%CI 23 - 54 in 42 months comparatively to PrEP interventions, that resulted in 41 (95%CI 28 - 67 individuals receiving antiretrovirals in order to prevent one case of HIV infection at 36 months for men and serodiscordant couples. PEP interventions are associated with protective effects estimated at 81%. Lack of trials evaluating PEP prevents estimate of NNT.Conclusion:The estimate of the NNT can be a helpful parameter in the comparison between the effectiveness of different behavioral and biomedical HIV prevention strategies. Studies evaluating the benefit and safety of combined behavioral and biomedical interventions are needed, especially considering the attributable fraction of each component. Integration of behavioral and biomedical interventions is required to achieve complete suppression of the virus, and thus reducing viral replication, infectivity and the number of cases.

  17. Sexual risk reduction among Zambian couples | Jones | SAHARA-J ...

    African Journals Online (AJOL)

    Zambia has over 1 million HIV infections nationwide and an urban prevalence rate of 23%. This study compared the impact of male involvement in multiple and single session risk reduction interventions among inconsistent condom users in Zambia and the role of serostatus among HIV-seropositive and serodiscordant ...

  18. High rates of HIV seroconversion in pregnant women and low reported levels of HIV testing among male partners in Southern Mozambique: results from a mixed methods study.

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    Caroline De Schacht

    Full Text Available INTRODUCTION: Prevention of acute HIV infections in pregnancy is required to achieve elimination of pediatric HIV. Identification and support for HIV negative pregnant women and their partners, particularly serodiscordant couples, are critical. A mixed method study done in Southern Mozambique estimated HIV incidence during pregnancy, associated risk factors and factors influencing partner's HIV testing. METHODS: Between April 2008 and November 2011, a prospective cohort of 1230 HIV negative pregnant women was followed during pregnancy. A structured questionnaire, HIV testing, and collection of dried blood spots were done at 2-3 scheduled visits. HIV incidence rates were calculated by repeat HIV testing and risk factors assessed by Poisson regression. A qualitative study including 37 individual interviews with men, women, and nurses and 11 focus group discussions (n = 94 with men, women and grandmothers explored motivators and barriers to uptake of male HIV testing. RESULTS: HIV incidence rate was estimated at 4.28/100 women-years (95%CI: 2.33-7.16. Significant risk factors for HIV acquisition were early sexual debut (RR 3.79, 95%CI: 1.04-13.78, p = 0.04 and living in Maputo Province (RR 4.35, 95%CI: 0.97-19.45, p = 0.05. Nineteen percent of women reported that their partner had tested for HIV (93% knew the result with 8/213 indicating an HIV positive partner, 56% said their partner had not tested and 19% did not know their partner test status. Of the 14 seroconversions, only one reported being in a serodiscordant relationship. Fear of discrimination or stigma was reported as a key barrier to male HIV testing, while knowing the importance of getting tested and receiving care was the main motivator. CONCLUSIONS: HIV incidence during pregnancy is high in Southern Mozambique, but knowledge of partners' HIV status remains low. Knowledge of both partners' HIV status is critical for maximal effectiveness of prevention and treatment services to reach

  19. Beyond HIV-serodiscordance: Partnership communication dynamics that affect engagement in safer conception care.

    Science.gov (United States)

    Matthews, Lynn T; Burns, Bridget F; Bajunirwe, Francis; Kabakyenga, Jerome; Bwana, Mwebesa; Ng, Courtney; Kastner, Jasmine; Kembabazi, Annet; Sanyu, Naomi; Kusasira, Adrine; Haberer, Jessica E; Bangsberg, David R; Kaida, Angela

    2017-01-01

    We explored acceptability and feasibility of safer conception methods among HIV-affected couples in Uganda. We recruited HIV-positive men and women on antiretroviral therapy (ART) ('index') from the Uganda Antiretroviral Rural Treatment Outcomes cohort who reported an HIV-negative or unknown-serostatus partner ('partner'), HIV-serostatus disclosure to partner, and personal or partner desire for a child within two years. We conducted in-depth interviews with 40 individuals from 20 couples, using a narrative approach with tailored images to assess acceptability of five safer conception strategies: ART for the infected partner, pre-exposure prophylaxis (PrEP) for the uninfected partner, condomless sex timed to peak fertility, manual insemination, and male circumcision. Translated and transcribed data were analyzed using thematic analysis. 11/20 index participants were women, median age of 32.5 years, median of 2 living children, and 80% had HIV-RNA perception: Participants had disparate understandings of HIV transmission and disagreed on the acceptable level of HIV risk to meet reproductive goals. (4) Partnership commitment: Participants revealed significant discord in perceptions of partnership commitment. All four types of partnership miscommunication introduced constraints to autonomous reproductive decision-making, particularly for women. Such miscommunication was common, as only 2 of 20 partnerships in our sample were mutually-disclosed with agreement across all four communication themes. Enthusiasm for safer conception programming is growing. Our findings highlight the importance of addressing gendered partnership communication regarding HIV disclosure, reproductive goals, acceptable HIV risk, and commitment, alongside technical safer conception advice. Failing to consider partnership dynamics across these domains risks limiting reach, uptake, adherence to, and retention in safer conception programming.

  20. Differences in knowledge, attitudes and behaviors of Israeli HIV-uninfected gay men in HIV-discordant vs. concordant steady relationships.

    Science.gov (United States)

    Tairy, Daniel; Levy, Itzchak; Turner, Dan; Livnat, Yuval; Mor, Zohar

    2018-06-01

    HIV-discordant gay male couples may play an important role in HIV-transmissions. This cross-sectional study compared the knowledge, attitudes and sexual behaviors of HIV-uninfected gay men, between those in HIV-discordant and those in HIV-concordant steady relationships. Anonymous questionnaires were distributed electronically in designated gay-related internet sites and in AIDS-clinics in 2015. The dependent variable was defined as a steady relationship of an HIV-uninfected man with an HIV-infected partner. Risky sexual behavior was defined as unprotected anal intercourse (UAI) with a sex partner whose HIV-status was either positive or unknown. Of 2,319 responders, 460 (20%) were HIV-uninfected gay men in steady relationships, of whom 72 were in HIV-discordant relationships and 388 were in HIV-concordant relationships. Those in HIV-discordant relationships presented better established knowledge regarding HIV-transmission, more lenient attitudes regarding UAI, and reported being involved in riskier sexual behavior, both within and outside their steady relationship compared to men in HIV-concordant relationships. UAI was performed by 48% of the HIV-discordant couples and was associated with the use of sero-positioning strategy and with achieving undetectable viral-load. These findings reflect the complexity of constant use of condoms during long-term sero-discordant relationships. Targeted interventions for HIV-prevention in HIV-discordant couples should be employed for balancing the partners' desire for intimacy and sexual pleasure in the relationship, while reducing the risk for acquiring HIV. ART: Antiretroviral therapy; PEP: Post exposure prophylaxis; PrEP: Pre exposure prophylaxis; STI: Sexually transmitted infections; UAI: Unprotected anal intercourse.

  1. Internalized stigma and HIV status disclosure among HIV-positive black men who have sex with men.

    Science.gov (United States)

    Overstreet, Nicole M; Earnshaw, Valerie A; Kalichman, Seth C; Quinn, Diane M

    2013-01-01

    Black men who have sex with men (BMSM) are severely affected by the HIV epidemic, yet research on the relationship between HIV stigma and status disclosure is relatively limited among this population. Within this epidemic, internalized HIV stigma, the extent to which people living with HIV/AIDS endorse the negative beliefs associated with HIV as true of themselves, can negatively shape interpersonal outcomes and have important implications for psychological and physical health. In a sample of HIV-positive BMSM (N=156), the current study examined the effect of internalized stigma on HIV status disclosure to sexual partners, which can inform sexual decision-making in serodiscordant couples, and HIV status disclosure to family members, which can be beneficial in minimizing the psychological distress associated with HIV. Results revealed that greater internalized stigma was associated with less HIV status disclosure to participants' last sexual partner and to family members. Findings from this study provide evidence that internalized negative beliefs about one's HIV status are linked to adverse interpersonal consequences. Implications of these findings are discussed with regard to prevention and intervention efforts to reduce HIV stigmatization.

  2. Pre-exposure prophylaxis for HIV-1 prevention does not diminish the pregnancy prevention effectiveness of hormonal contraception.

    Science.gov (United States)

    Murnane, Pamela M; Heffron, Renee; Ronald, Allan; Bukusi, Elizabeth A; Donnell, Deborah; Mugo, Nelly R; Were, Edwin; Mujugira, Andrew; Kiarie, James; Celum, Connie; Baeten, Jared M

    2014-07-31

    For women at risk of HIV-1, effective contraception and effective HIV-1 prevention are global priorities. In a clinical trial of pre-exposure prophylaxis (PrEP) for HIV-1 prevention in HIV-1-serodiscordant couples, we estimated the effectiveness of hormonal contraceptives (oral contraceptive pills, injectable depot medroxyprogesterone acetate, and hormonal implants) for pregnancy prevention relative to no contraception among 1785 HIV-1-uninfected women followed up to 36 months. We compared the effectiveness of each method among women assigned PrEP versus placebo. Contraception was not required for participation, but was offered on-site and was recorded monthly; incident pregnancy was determined by monthly urine testing. For women using no contraception, overall pregnancy incidence was 15.4% per year. Women reporting oral contraceptive use had comparable pregnancy incidence to women using no contraception, and this lack of contraceptive effectiveness was similar for those assigned PrEP and placebo (17.7 and 10.0% incidence per year, respectively; P-value for difference in effect by PrEP use = 0.24). Women reporting injectable contraception had reduced pregnancy incidence compared to those reporting no contraception, which did not differ by arm (PrEP 5.1%, placebo 5.3% per year; P-value for difference = 0.47). Contraceptive effectiveness was highest among women using implants (pregnancy incidence <1% per year in both arms). PrEP had no adverse impact on hormonal contraceptive effectiveness for pregnancy prevention. As seen previously in similar populations, women reporting contraceptive pill use had little protection from pregnancy, possibly due to poor adherence. Injectable or implantable hormonal contraception and PrEP provide effective prevention for pregnancy and HIV-1.

  3. Sexual behaviour of heterosexual men and women receiving antiretroviral pre-exposure prophylaxis for HIV prevention: a longitudinal analysis.

    Science.gov (United States)

    Mugwanya, Kenneth K; Donnell, Deborah; Celum, Connie; Thomas, Katherine K; Ndase, Patrick; Mugo, Nelly; Katabira, Elly; Ngure, Kenneth; Baeten, Jared M

    2013-12-01

    Scarce data are available to assess sexual behaviour of individuals using antiretroviral pre-exposure prophylaxis for HIV prevention. Increased sexual risk taking by individuals using effective HIV prevention strategies, like pre-exposure prophylaxis, could offset the benefits of HIV prevention. We studied whether the use of pre-exposure prophylaxis in HIV-uninfected men and women in HIV-serodiscordant couples was associated with increased sexual risk behaviour. We undertook a longitudinal analysis of data from the Partners PrEP Study, a double-blind, randomised, placebo-controlled trial of daily oral pre-exposure prophylaxis among HIV-uninfected partners of heterosexual HIV-serodiscordant couples (n=3163, ≥18 years of age). Efficacy for HIV prevention was publicly reported in July 2011, and participants continued monthly follow-up thereafter. We used regression analyses to compare the frequency of sex-unprotected by a condom-during the 12 months after compared with the 12 months before July 2011, to assess whether knowledge of pre-exposure prophylaxis efficacy for HIV prevention caused increased sexual risk behaviour. We analysed 56 132 person-months from 3024 HIV-uninfected individuals (64% male). The average frequency of unprotected sex with the HIV-infected study partner was 59 per 100 person-months before unmasking versus 53 after unmasking; we recorded no immediate change (p=0·66) or change over time (p=0·25) after July, 2011. We identified a significant increase in unprotected sex with outside partners after July, 2011, but the effect was small (average of 6·8 unprotected sex acts per year vs 6·2 acts in a predicted counterfactual scenario had patients remained masked, p=0·04). Compared with before July, 2011, we noted no significant increase in incident sexually transmitted infections or pregnancy after July, 2011. Pre-exposure prophylaxis, provided as part of a comprehensive prevention package, might not result in substantial changes in risk

  4. Intimate partner sexual and physical violence among women in Togo, West Africa: Prevalence, associated factors, and the specific role of HIV infection

    Directory of Open Access Journals (Sweden)

    Juan Burgos-Soto

    2014-05-01

    Full Text Available Background: A substantial proportion of newly diagnosed HIV infections in sub-Saharan Africa occur within serodiscordant cohabiting heterosexual couples. Intimate partner violence is a major concern for couple-oriented HIV preventive approaches. This study aimed at estimating the prevalence and associated factors of intimate partner physical and sexual violence among HIV-infected and -uninfected women in Togo. We also described the severity and consequences of this violence as well as care-seeking behaviors of women exposed to intimate partner violence. Methods: A cross-sectional survey was conducted between May and July 2011 within Sylvanus Olympio University Hospital in Lomé. HIV-infected women attending HIV care and uninfected women attending postnatal care and/or children immunization visits were interviewed. Intimate partner physical and sexual violence and controlling behaviors were assessed using an adapted version of the WHO Multi-country study on Women's Health and Life Events questionnaire. Results: Overall, 150 HIV-uninfected and 304 HIV-infected women accepted to be interviewed. The prevalence rates of lifetime physical and sexual violence among HIV-infected women were significantly higher than among uninfected women (63.1 vs. 39.3%, p<0.01 and 69.7 vs. 35.3%, p<0.01, respectively. Forty-two percent of the women reported having ever had physical injuries as a consequence of intimate partner violence. Among injured women, only one-third had ever disclosed real causes of injuries to medical staff and none of them had been referred to local organizations to receive appropriate psychological support. Regardless of HIV status and after adjustment on potential confounders, the risk of intimate partner physical and sexual violence was strongly and significantly associated with male partner multi-partnership and early start of sexual life. Among uninfected women, physical violence was significantly associated with gender submissive

  5. Enhanced prenatal HIV couple oriented counselling session and couple communication about HIV (ANRS 12127 Prenahtest Trial)

    NARCIS (Netherlands)

    Plazy, M.; Orne-Gliemann, J.; Balestre, E.; Miric, M.; Darak, S.; Butsashvili, M.; Tchendjou, P.; Dabis, F.; du Lou, A. Desgrees

    Background. - The Prenahtest study investigated the efficacy of a couple-oriented HIV counselling session (COC) in encouraging couple HIV counselling and testing, and improving intra-couple communication about sexual and reproductive health. We report here on the effect of COC on intra-couple

  6. Reassessment of HIV-1 Acute Phase Infectivity: Accounting for Heterogeneity and Study Design with Simulated Cohorts

    Science.gov (United States)

    Bellan, Steve E.; Dushoff, Jonathan; Galvani, Alison P.; Meyers, Lauren Ancel

    2015-01-01

    Background The infectivity of the HIV-1 acute phase has been directly measured only once, from a retrospectively identified cohort of serodiscordant heterosexual couples in Rakai, Uganda. Analyses of this cohort underlie the widespread view that the acute phase is highly infectious, even more so than would be predicted from its elevated viral load, and that transmission occurring shortly after infection may therefore compromise interventions that rely on diagnosis and treatment, such as antiretroviral treatment as prevention (TasP). Here, we re-estimate the duration and relative infectivity of the acute phase, while accounting for several possible sources of bias in published estimates, including the retrospective cohort exclusion criteria and unmeasured heterogeneity in risk. Methods and Findings We estimated acute phase infectivity using two approaches. First, we combined viral load trajectories and viral load-infectivity relationships to estimate infectivity trajectories over the course of infection, under the assumption that elevated acute phase infectivity is caused by elevated viral load alone. Second, we estimated the relative hazard of transmission during the acute phase versus the chronic phase (RHacute) and the acute phase duration (d acute) by fitting a couples transmission model to the Rakai retrospective cohort using approximate Bayesian computation. Our model fit the data well and accounted for characteristics overlooked by previous analyses, including individual heterogeneity in infectiousness and susceptibility and the retrospective cohort's exclusion of couples that were recorded as serodiscordant only once before being censored by loss to follow-up, couple dissolution, or study termination. Finally, we replicated two highly cited analyses of the Rakai data on simulated data to identify biases underlying the discrepancies between previous estimates and our own. From the Rakai data, we estimated RHacute = 5.3 (95% credibility interval [95% CrI]: 0

  7. Nurturing the Continuum of HIV Testing, Treatment and Prevention Matrix Cascade in Reducing HIV Transmission.

    Science.gov (United States)

    Yah, Clarence S

    2017-11-01

    Despite the shift in antiretroviral therapy (ARVs) eligibility cascade from CD4 ≤ 200 to CD4 ≤ 350 to CD4 ≤ 500 mm 3 , HIV related morbidity and mortality continue to escalate annually, as do HIV infections. The new paradigm of treatment for all HIV positives individual irrespective of CD4 count may significantly reduce HIV and related illnesses. The author assumes that all HIV infected partners should be eligible for HIV treatment and care, irrespective of CD4 count. A second assumption is that high risk HIV negative partners have free access to continuum of HIV pre-exposure prophylaxis (PrEP), post exposure prophylaxis (PEP) and other prevention packages. A literature review search was used to extract evidence-based ARVs-HIV treatment and prevention interventions among HIV positives and high risk partners respectively. Only articles published in English and indexed in journal nuclei were used for the study. The information was used to nurture understanding of HIV treatment and prevention approaches as well as HIV incidence multiplier effect among HIV serodiscordant partners. The imputed HIV incident reference was assumed at 1.2 per 100 person-years (2). This was based on the imputation that retention in care, adherence and other predetermined factors are functions of an effective health care delivery system. The model showed a reduced HIV transmission from 1.2 per 100 person-years to 1.032 per 100 person-years in 6 months. The average threshold period of HIV suppressed partners on ARVs to an undetectable level. The combined multiplier protective-effect probability of transmitting HIV from HIV positive partners on ARVs-suppressed viremic load to HIV negative partners on PrEP/PEP-prevention was detected at 86. The model showed a significant reduction in HIV incidence. Placing serodiscordant sexual partners in HIV treatment and prevention plays a significant role in reducing and controlling HIV infection. Therefore, the policy of enrolling all HIV positives

  8. Optimizing Prevention of HIV and Unplanned Pregnancy in Discordant African Couples.

    Science.gov (United States)

    Wall, Kristin M; Kilembe, William; Vwalika, Bellington; Haddad, Lisa B; Khu, Naw Htee; Brill, Ilene; Onwubiko, Udodirim; Chomba, Elwyn; Tichacek, Amanda; Allen, Susan

    2017-08-01

    Dual method use, which combines condoms with a more effective modern contraceptive to optimize prevention of HIV and unplanned pregnancy, is underutilized in high-risk heterosexual couples. Heterosexual HIV-discordant Zambian couples were enrolled from couples' voluntary HIV counseling and testing services into an open cohort with 3-monthly follow-up (1994-2012). Relative to dual method use, defined as consistent condom use plus modern contraception, we examine predictors of (1) condom-only use (suboptimal pregnancy prevention) or (2) modern contraceptive use with inconsistent condom use (effective pregnancy prevention and suboptimal HIV prevention). Among 3,049 couples, dual method use occurred in 28% of intervals in M+F- and 23% in M-F+, p HIV+ (adjusted hazard ratio, aHR = 1.15); baseline oral contraceptive pill (aHR = 0.76), injectable (aHR = 0.48), or implant (aHR = 0.60) use; woman's age (aHR = 1.04 per 5 years) and lifetime number of sex partners (aHR = 1.01); postpartum periods (aHR = 1.25); and HIV stage of the index partner III/IV versus I (aHR = 1.10). Predictors (p HIV+ male circumcision (aHR = 1.51), while time-varying implant use was associated with more consistent condom use (aHR = 0.80). Three-quarters of follow-up intervals did not include dual method use. This highlights the need for counseling to reduce unintended pregnancy and HIV transmission and enable safer conception.

  9. Pregnancy and transmission of Human Immunodefiency Virus (HIV ...

    African Journals Online (AJOL)

    Background: Serodiscordant couples, have been used to study heterosexual transmission risk because of the high frequency of sexual acts that occur in stable relationships. The hormonal changes during pregnancy could influence heterosexual transmission in serodiscordant relationships. The prevalence of ...

  10. Experience of sexual violence among women in HIV discordant unions after voluntary HIV counselling and testing

    Science.gov (United States)

    Emusu, Donath; Ivankova, Nataliya; Jolly, Pauline; Kirby, Russell; Foushee, Herman; Wabwire-Mangen, Fred; Katongole, Drake; Ehiri, John

    2009-01-01

    HIV-serodiscordant relationships are those in which one partner is infected with HIV while the other is not. We investigated experiences of sexual violence among women in HIV discordant unions attending HIV post-test club services in Uganda. A volunteer sample of 26 women from three AIDS Information Centres in Uganda who reported having experienced sexual violence in a larger epidemiological study were interviewed, using the qualitative critical incident technique. Data were analysed using TEXTPACK, a software application for computer-assisted content analysis. Incidents of sexual violence narrated by the women included use of physical force and verbal threats. Overall, four themes that characterise the women’s experience of sexual violence emerged from the analysis: knowledge of HIV test results, prevalence of sexual violence, vulnerability and proprietary views and reactions to sexual violence. Alcohol abuse by the male partners was an important factor in the experience of sexual violence among the women. Their experiences evoked different reactions and feelings, including concern over the need to have children, fear of infection, desire to separate from their spouses/partners, helplessness, anger and suicidal tendencies. HIV counselling and testing centres should be supported with the capacity to address issues related to sexual violence for couples who are HIV discordant. PMID:20024712

  11. Effects of early versus delayed initiation of antiretroviral treatment on clinical outcomes of HIV-1 infection: results from the phase 3 HPTN 052 randomised controlled trial

    Science.gov (United States)

    Grinsztejn, Beatriz; Hosseinipour, Mina C; Ribaudo, Heather J; Swindells, Susan; Eron, Joseph; Chen, Ying Q; Wang, Lei; Ou, San-San; Anderson, Maija; McCauley, Marybeth; Gamble, Theresa; Kumarasamy, Nagalingeshwaran; Hakim, James G; Kumwenda, Johnstone; Pilotto, Jose H S; Godbole, Sheela V; Chariyalertsak, Suwat; de Melo, Marineide Gonçalves; Mayer, Kenneth H; Eshleman, Susan H; Piwowar-Manning, Estelle; Makhema, Joseph; Mills, Lisa A; Panchia, Ravindre; Sanne, Ian; Gallant, Joel; Hoffman, Irving; Taha, Taha E; Nielsen-Saines, Karin; Celentano, David; Essex, Max; Havlir, Diane; Cohen, Myron S

    2014-01-01

    Summary Background Use of antiretroviral treatment for HIV-1 infection has decreased AIDS-related morbidity and mortality and prevents sexual transmission of HIV-1. However, the best time to initiate antiretroviral treatment to reduce progression of HIV-1 infection or non-AIDS clinical events is unknown. We reported previously that early antiretroviral treatment reduced HIV-1 transmission by 96%. We aimed to compare the effects of early and delayed initiation of antiretroviral treatment on clinical outcomes. Methods The HPTN 052 trial is a randomised controlled trial done at 13 sites in nine countries. We enrolled HIV-1-serodiscordant couples to the study and randomly allocated them to either early or delayed antiretroviral treatment by use of permuted block randomisation, stratified by site. Random assignment was unblinded. The HIV-1-infected member of every couple initiated antiretroviral treatment either on entry into the study (early treatment group) or after a decline in CD4 count or with onset of an AIDS-related illness (delayed treatment group). Primary events were AIDS clinical events (WHO stage 4 HIV-1 disease, tuberculosis, and severe bacterial infections) and the following serious medical conditions unrelated to AIDS: serious cardiovascular or vascular disease, serious liver disease, end-stage renal disease, new-onset diabetes mellitus, and non-AIDS malignant disease. Analysis was by intention-to-treat. This trial is registered with ClinicalTrials.gov, number NCT00074581. Findings 1763 people with HIV-1 infection and a serodiscordant partner were enrolled in the study; 886 were assigned early antiretroviral treatment and 877 to the delayed treatment group (two individuals were excluded from this group after randomisation). Median CD4 counts at randomisation were 442 (IQR 373–522) cells per μL in patients assigned to the early treatment group and 428 (357–522) cells per μL in those allocated delayed antiretroviral treatment. In the delayed group

  12. Couple interdependence impacts HIV-related health behaviours among pregnant couples in southwestern Kenya: a qualitative analysis.

    Science.gov (United States)

    Rogers, Anna Joy; Achiro, Lillian; Bukusi, Elizabeth A; Hatcher, Abigail M; Kwena, Zachary; Musoke, Pamela L; Turan, Janet M; Weke, Elly; Darbes, Lynae A

    2016-01-01

    HIV infection is frequently transmitted within stable couple partnerships. In order to prevent HIV acquisition in HIV-negative couples, as well as improve coping in couples with an HIV-positive diagnosis, it has been suggested that interventions be aimed at strengthening couple relationships, in addition to addressing individual behaviours. However, little is known about factors that influence relationships to impact joint decision-making related to HIV. We conducted qualitative in-depth interviews with 40 pregnant women and 40 male partners in southwestern Kenya, an area of high HIV prevalence. Drawing from the interdependence model of communal coping and health behaviour change, we employed thematic analysis methods to analyze interview transcripts in Dedoose software with the aim of identifying key relationship factors that could contribute to the development of a couples-based intervention to improve health outcomes for pregnant women and their male partners. In accordance with the interdependence model, we found that couples with greater relationship-centred motivations described jointly engaging in more health-enhancing behaviours, such as couples HIV testing, disclosure of HIV status, and cooperation to improve medication and clinic appointment adherence. These couples often had predisposing factors such as stronger communication skills and shared children, and were less likely to face potential challenges such as polygamous marriages, wife inheritance, living separately, or financial difficulties. For HIV-negative couples, joint decision-making helped them face the health threat of acquiring HIV together. For couples with an HIV-positive diagnosis, communal coping helped reduce risk of interspousal transmission and improve long-term health prospects. Conversely, participants felt that self-centred motivations led to more concurrent sexual partnerships, reduced relationship satisfaction, and mistrust. Couples who lacked interdependence were more likely to

  13. Hormonal contraception does not increase women's HIV acquisition risk in Zambian discordant couples, 1994-2012.

    Science.gov (United States)

    Wall, Kristin M; Kilembe, William; Vwalika, Bellington; Htee Khu, Naw; Brill, Ilene; Chomba, Elwyn; Johnson, Brent A; Haddad, Lisa; Tichacek, Amanda; Allen, Susan

    2015-06-01

    To determine the impact of hormonal contraceptive methods on risk of HIV acquisition among HIV-negative women cohabiting with HIV-positive male partners. From 1994-2012, HIV discordant couples recruited from a couples' voluntary HIV counseling and testing center in Lusaka, Zambia were followed longitudinally. HIV-negative partners were tested quarterly. This analysis is restricted to couples in which the man was HIV-positive and the woman was HIV-negative at enrollment and the man was not on antiretroviral treatment. Multivariate Cox models evaluated associations between time-varying contraceptive methods and HIV acquisition among women. Sensitivity analyses explored exposure misclassification and time-varying confounder mediation. Among 1393 couples, 252 incident infections occurred in women over 2842 couple-years (8.9 infections per 100 couple-years; 95% CI, 7.8-10.0). Multivariate Cox models indicated that neither injectable [adjusted hazard ratio (aHR)=1.2; 95% CI, 0.8-1.7], oral contraceptive pill (OCP, aHR=1.3; 95% CI, 0.9-1.8), or implant (aHR=1.1; 95% CI, 0.5-2.2) use was significantly associated with HIV acquisition relative to non-hormonal contraception controlling for woman's age, literacy and time-varying measures of genital ulceration/inflammation. This remained true when only looking at the subset of infections acquired from the spouse (82% of infections) and additionally controlling for baseline HIV viral load of the male partner, pregnancy status, and time-varying measures of sperm on a vaginal swab wet prep and self-reported unprotected sex. OCP and injectable users reported more unprotected sex (pcontraception and HIV acquisition risk in women. Condom use and reinforced condom counseling should always be recommended for HIV discordant couples. HIV testing of sex partners together is critical to establish HIV risk, ascertain couple fertility intentions and counsel appropriately. These findings add to a controversial literature and uniquely address

  14. Southern African guidelines on the safe use of pre-exposure prophylaxis in persons at risk of acquiring HIV-1 infection

    Directory of Open Access Journals (Sweden)

    Linda-Gail Bekker

    2016-03-01

    Full Text Available The Southern African HIV Clinicians Society published its first set of oral pre-exposure prophylaxis (PrEP guidelines in June 2012 for men who have sex with men (MSM who are at risk of HIV infection. With the flurry of data that has been generated in PrEP clinical research since the first guideline, it became evident that there was a need to revise and expand the PrEP guidelines with new evidence of safety and efficacy of PrEP in several populations, including MSM, transgender persons, heterosexual men and women, HIV-serodiscordant couples and people who inject drugs. This need is particularly relevant following the World Health Organization (WHO Consolidated Treatment Guidelines released in September 2015. These guidelines advise that PrEP is a highly effective, safe, biomedical option for HIV prevention that can be incorporated with other combination prevention strategies in Southern Africa, given the high prevalence of HIV in the region. PrEP should be tailored to populations at highest risk of HIV acquisition, whilst further data from studies in the region accrue to guide optimal deployment to realise the greatest impact regionally. PrEP may be used intermittently during periods of perceived HIV acquisition risk, rather than continually and lifelong, as is the case with antiretroviral treatment. Recognition and accurate measurement of potential risk in individuals and populations also warrants discussion, but are not extensively covered in these guidelines.

  15. Southern African guidelines on the safe use of pre-exposure prophylaxis in persons at risk of acquiring HIV-1 infection

    Science.gov (United States)

    Rebe, Kevin; Venter, Francois; Maartens, Gary; Moorhouse, Michelle; Conradie, Francesca; Wallis, Carole; Black, Vivian; Harley, Beth; Eakles, Robyn

    2016-01-01

    The Southern African HIV Clinicians Society published its first set of oral pre-exposure prophylaxis (PrEP) guidelines in June 2012 for men who have sex with men (MSM) who are at risk of HIV infection. With the flurry of data that has been generated in PrEP clinical research since the first guideline, it became evident that there was a need to revise and expand the PrEP guidelines with new evidence of safety and efficacy of PrEP in several populations, including MSM, transgender persons, heterosexual men and women, HIV-serodiscordant couples and people who inject drugs. This need is particularly relevant following the World Health Organization (WHO) Consolidated Treatment Guidelines released in September 2015. These guidelines advise that PrEP is a highly effective, safe, biomedical option for HIV prevention that can be incorporated with other combination prevention strategies in Southern Africa, given the high prevalence of HIV in the region. PrEP should be tailored to populations at highest risk of HIV acquisition, whilst further data from studies in the region accrue to guide optimal deployment to realise the greatest impact regionally. PrEP may be used intermittently during periods of perceived HIV acquisition risk, rather than continually and lifelong, as is the case with antiretroviral treatment. Recognition and accurate measurement of potential risk in individuals and populations also warrants discussion, but are not extensively covered in these guidelines. PMID:29568613

  16. Erectile dysfunction drug receipt, risky sexual behavior and sexually transmitted diseases in HIV-infected and HIV-uninfected men.

    Science.gov (United States)

    Cook, Robert L; McGinnis, Kathleen A; Samet, Jeffrey H; Fiellin, David A; Rodriguez-Barradas, Maria C; Rodriquez-Barradas, Maria C; Kraemer, Kevin L; Gibert, Cynthia L; Braithwaite, R Scott; Goulet, Joseph L; Mattocks, Kristin; Crystal, Stephen; Gordon, Adam J; Oursler, Krisann K; Justice, Amy C

    2010-02-01

    Health care providers may be concerned that prescribing erectile dysfunction drugs (EDD) will contribute to risky sexual behavior. To identify characteristics of men who received EDD prescriptions, determine whether EDD receipt is associated with risky sexual behavior and sexually transmitted diseases (STDs), and determine whether these relationships vary for certain sub-groups. Cross-sectional study. Two thousand seven hundred and eighty-seven sexually-active, HIV-infected and HIV-uninfected men recruited from eight Veterans Health Affairs outpatient clinics. Data were obtained from participant surveys, electronic medical records, and administrative pharmacy data. EDD receipt was defined as two or more prescriptions for an EDD, risky sex as having unprotected sex with a partner of serodiscordant or unknown HIV status, and STDs, according to self-report. Overall, 28% of men received EDD in the previous year. Eleven percent of men reported unprotected sex with a serodiscordant/unknown partner in the past year (HIV-infected 15%, HIV-uninfected 6%, P sexual behavior (11% vs. 10%, p = 0.9) and STDs (7% vs 7%, p = 0.7). In multivariate analyses, EDD receipt was not significantly associated with risky sexual behavior or STDs in the entire sample or in subgroups of substance users or men who had sex with men. EDD receipt was common but not associated with risky sexual behavior or STDs in this sample of HIV-infected and uninfected men. However, risky sexual behaviors persist in a minority of HIV-infected men, indicating ongoing need for prevention interventions.

  17. HIV discordant couples: What is new? | Kongnyuy | Clinics in Mother ...

    African Journals Online (AJOL)

    We reviewed the existing literature on the HIV discordant couples: determinants of seroconversion, reproductive options, ethical issues and future perspectives. About 10% to 20% of couples in Sub-Saharan Africa are HIV discordant. Factors influencing the risk of seroconversion in HIV discordant couples include the ...

  18. Use of Condoms among Human Immunodeficiency Virus Positive Women Attending Antenatal Clinic in Nnewi, South East Nigeria.

    Science.gov (United States)

    Udigwe, Go; Mbachu, Ii; Onyegbule, Oa; Oguaka, V

    2014-09-01

    Consistent use of condom provides protection from transmission of human immunodeficiency virus (HIV) infection in couples with sero-discordant HIV status. It also protects against acquiring other strains in HIV positive concordant couples. This study evaluated the use of barrier method of contraception among HIV patients. This was a descriptive cross-sectional study conducted among pregnant women in Nnamdi Azikiwe University Teaching Hospital Nnewi. An interviewer administered questionnaire was used to obtain relevant information from the subjects. Data was analyzed using SPSS software version 20.0 (Chicago, IL, USA, August 2011). A total of 126 HIV positive pregnant women participated in this study. The mean age of the women was 30.4 (5) years while the mean parity was 2.6 (1). All the patients had at least primary education with 63.5% (80/126) having secondary education as the highest educational attainment while 87.3% (110/126) were in monogamous marriage. The partner's HIV status showed that 41.3% (52/126) tested negative to HIV antibodies while 42.8% (54/126) tested positive to HIV antibodies and 15.9% (20/126) do not know partner's HIV status. Only 61.9% (78/126) of the couples use condom during sexual intercourse. Further analysis showed that 26.2% (33/126) use condom consistently except during timed intercourse for conception. There was significant association between type of relationship and use of barrier method of contraception. There was no significant association between sero-discordant couples and highest educational status with use of barrier method of conception. Condom use among HIV positive couples is low and raises great concern on transmission of the virus to partners and babies born to positive mothers.

  19. Hormonal contraception does not increase women's HIV acquisition risk in Zambian discordant couples, 1994–2012

    Science.gov (United States)

    Wall, Kristin M.; Kilembe, William; Vwalika, Bellington; Khu, Naw Htee; Brill, Ilene; Chomba, Elwyn; Johnson, Brent A.; Haddad, Lisa; Tichacek, Amanda; Allen, Susan

    2015-01-01

    Objective To determine the impact of hormonal contraceptive methods on risk of HIV acquisition among HIV-negative women cohabiting with HIV-positive male partners. Study design From 1994–2012, HIV discordant couples recruited from a couples’ voluntary HIV counseling and testing center in Lusaka, Zambia were followed longitudinally. HIV-negative partners were tested quarterly. This analysis is restricted to couples in which the man was HIV-positive and the woman was HIV-negative at enrollment and the man was not on antiretroviral treatment. Multivariate Cox models evaluated associations between time-varying contraceptive methods and HIV acquisition among women. Sensitivity analyses explored exposure misclassification and time-varying confounder mediation. Results Among 1393 couples, 252 incident infections occurred in women over 2842 couple-years (8.9 infections per 100 couple-years; 95% CI, 7.8–10.0). Multivariate Cox models indicated that neither injectable [adjusted hazard ratio (aHR)=1.2; 95% CI, 0.8–1.7], oral contraceptive pill (OCP, aHR=1.3; 95% CI, 0.9–1.8), or implant (aHR=1.1; 95% CI, 0.5–2.2) use was significantly associated with HIV acquisition relative to non-hormonal contraception controlling for woman's age, literacy and time-varying measures of genital ulceration/inflammation. This remained true when only looking at the subset of infections acquired from the spouse (82% of infections) and additionally controlling for baseline HIV viral load of the male partner, pregnancy status, and time-varying measures of sperm on a vaginal swab wet prep and self-reported unprotected sex. OCP and injectable users reported more unprotected sex (pcontraception and HIV acquisition risk in women. Condom use and reinforced condom counseling should always be recommended for HIV discordant couples. HIV testing of sex partners together is critical to establish HIV risk, ascertain couple fertility intentions and counsel appropriately. Implications These findings

  20. Prevalence of HIV infection among premarital couples in southeast ...

    African Journals Online (AJOL)

    The Catholic Church in Nigeria offers premarital HIV screening to couples, yet instances of voluntary screening are rare in southeast Nigeria. This study examines the contribution of such tests to HIV detection, and evaluates the prevalence of HIV infection in southeast Nigeria among couples who are planning to marry.

  1. Acyclovir and Transmission of HIV-1 from Persons Infected with HIV-1 and HSV-2

    Science.gov (United States)

    Celum, Connie; Wald, Anna; Lingappa, Jairam R.; Magaret, Amalia S.; Wang, Richard S.; Mugo, Nelly; Mujugira, Andrew; Baeten, Jared M.; Mullins, James I.; Hughes, James P.; Bukusi, Elizabeth A.; Cohen, Craig R.; Katabira, Elly; Ronald, Allan; Kiarie, James; Farquhar, Carey; Stewart, Grace John; Makhema, Joseph; Essex, Myron; Were, Edwin; Fife, Kenneth H.; de Bruyn, Guy; Gray, Glenda E.; McIntyre, James A.; Manongi, Rachel; Kapiga, Saidi; Coetzee, David; Allen, Susan; Inambao, Mubiana; Kayitenkore, Kayitesi; Karita, Etienne; Kanweka, William; Delany, Sinead; Rees, Helen; Vwalika, Bellington; Stevens, Wendy; Campbell, Mary S.; Thomas, Katherine K.; Coombs, Robert W.; Morrow, Rhoda; Whittington, William L.H.; McElrath, M. Juliana; Barnes, Linda; Ridzon, Renee; Corey, Lawrence

    2010-01-01

    BACKGROUND Most persons who are infected with human immunodeficiency virus type 1 (HIV-1) are also infected with herpes simplex virus type 2 (HSV-2), which is frequently reactivated and is associated with increased plasma and genital levels of HIV-1. Therapy to suppress HSV-2 reduces the frequency of reactivation of HSV-2 as well as HIV-1 levels, suggesting that suppression of HSV-2 may reduce the risk of transmission of HIV-1. METHODS We conducted a randomized, placebo-controlled trial of suppressive therapy for HSV-2 (acyclovir at a dose of 400 mg orally twice daily) in couples in which only one of the partners was seropositive for HIV-1 (CD4 count, ≥250 cells per cubic millimeter) and that partner was also infected with HSV-2 and was not taking antiretroviral therapy at the time of enrollment. The primary end point was transmission of HIV-1 to the partner who was not initially infected with HIV-1; linkage of transmissions was assessed by means of genetic sequencing of viruses. RESULTS A total of 3408 couples were enrolled at 14 sites in Africa. Of the partners who were infected with HIV-1, 68% were women, and the baseline median CD4 count was 462 cells per cubic millimeter. Of 132 HIV-1 seroconversions that occurred after randomization (an incidence of 2.7 per 100 person-years), 84 were linked within couples by viral sequencing: 41 in the acyclovir group and 43 in the placebo group (hazard ratio with acyclovir, 0.92, 95% confidence interval [CI], 0.60 to 1.41; P = 0.69). Suppression with acyclovir reduced the mean plasma concentration of HIV-1 by 0.25 log10 copies per milliliter (95% CI, 0.22 to 0.29; P<0.001) and the occurrence of HSV-2–positive genital ulcers by 73% (risk ratio, 0.27; 95% CI, 0.20 to 0.36; P<0.001). A total of 92% of the partners infected with HIV-1 and 84% of the partners not infected with HIV-1 remained in the study for 24 months. The level of adherence to the dispensed study drug was 96%. No serious adverse events related to acyclovir

  2. Effectiveness of semen washing to prevent HIV transmission and assist pregnancy in HIV-discordant couples: a systematic review and meta-analysis

    Science.gov (United States)

    Zafer, Maryam; Horvath, Hacsi; Mmeje, Okeoma; van der Poel, Sheryl; Semprini, Augusto; Rutherford, George; Brown, Joelle

    2015-01-01

    Objective To evaluate the effectiveness of semen washing in HIV-discordant couples in which the male partner is infected Design Systematic review and meta-analysis Setting All countries Patient(s) Forty single-arm, open label studies among HIV-discordant couples that underwent intrauterine insemination (IUI) or in vitro fertilization (IVF) with or without intracytoplasmic sperm injection (ICSI) using washed semen Intervention(s) Semen washing followed by IUI, IVF, or IVF/ICSI Main outcome measure(s) Primary outcome: HIV transmission to HIV-uninfected women; secondary outcomes: HIV transmission to newborns and proportion of couples achieving a clinical pregnancy Result(s) No HIV transmission occurred in 11,585 cycles of assisted reproduction using washed semen among 3,994 women (95% confidence interval [CI] = 0–0.0001). Among the subset of HIV-infected men without plasma viral suppression at the time of semen washing, no HIV seroconversions occurred among 1,023 women following 2,863 cycles of assisted reproduction using washed semen (95%CI= 0–0.0006). Studies that measured HIV transmission to infants reported no cases of vertical transmission (0/1,026, 95% CI= 0–0.0029). Overall, 56.3% (2,357/4,184, 95%CI=54.8%–57.8%) of couples achieved a clinical pregnancy using washed semen. Conclusion(s) Semen washing appears to significantly reduce the risk of transmission in HIV-discordant couples desiring children, regardless of viral suppression in the male partner. There are no randomized, controlled studies or studies from low-income countries, especially those with a large burden of HIV. Continued development of lower-cost semen washing and assisted reproduction technologies is needed. Integration of semen washing into HIV prevention interventions could help further reduce the spread of HIV. PMID:26688556

  3. Premarital HIV Testing on Prospective Couples in A Teaching ...

    African Journals Online (AJOL)

    Premarital HIV Testing on Prospective Couples in A Teaching Hospital in Sub Saharan Africa. ... Background: Most religious bodies insist on premarital screening for prospective couples. Aim: To determine the level of voluntary screening, prevalence and risk factors of HIV among premarital couples. Material and methods: ...

  4. Determinants In HIV Counselling And Testing In Couples In North ...

    African Journals Online (AJOL)

    Determinants In HIV Counselling And Testing In Couples In North Rift Kenya. PO Ayuo, E Were, K Wools-Kaloustian, J Baliddawa, J Sidle, K Fife. Abstract. Background: Voluntary HIV counselling and testing (VCT) has been shown to be an acceptable and effective tool in the fight against HIV/AIDS. Couple HIV Counselling ...

  5. HIV-discordant couples

    African Journals Online (AJOL)

    Winnie

    2006-06-02

    Jun 2, 2006 ... These may broadly be divided into factors that affect the transmissibility of HIV between couples per sex act and factors influencing the number of sex acts during which exposure may occur. Examples of the former include use of condoms or other barrier methods and certain sexual behaviours, such as sex.

  6. Implementation of Couples' Voluntary HIV Counseling and Testing ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Couples' Voluntary HIV Counseling and Testing (CVCT) is an effective HIV ... Through this project, the Rwanda Zambia HIV Research Group will apply more than ... to provide support, training, and technical assistance to pilot the expansion of ...

  7. Implementation of Couples' Voluntary HIV Counseling and Testing ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Couples' Voluntary HIV Counseling and Testing (CVCT) is an effective HIV ... Through this project, the Rwanda Zambia HIV Research Group will apply more than 20 ... training, and technical assistance to pilot the expansion of CVCT in local ...

  8. Gender Differences in Depressive Symptoms Among HIV-Positive Concordant and Discordant Heterosexual Couples in China.

    Science.gov (United States)

    Li, Li; Liang, Li-Jung; Lin, Chunqing; Ji, Guoping; Xiao, Yongkang

    2017-03-01

    HIV seropositive individuals and their heterosexual partners/spouses, either seropositive or seronegative, are facing several mental health challenges. The objective of this study was to examine gender differences in depressive symptoms among HIV-positive concordant and HIV-discordant couples. We identified heterosexual couples from participants of a randomized controlled trial conducted in Anhui province, China. A total of 265 couples, comprising 129 HIV+ male/HIV- female couples, 98 HIV- male/HIV+ female couples, and 38 HIV-positive concordant couples, were included in the analyses. We collected data using the computer-assisted personal interview method. We used a linear mixed-effects regression model to assess whether gender differences in depressive symptoms varied across couple types. HIV-positive women reported a significantly higher level of depressive symptoms than their partners/spouses. HIV-positive women with HIV-positive partners had higher depressive symptoms than those with HIV-negative partners, whereas HIV-positive men reported similar levels of depressive symptoms regardless of their partners' serostatus. Among the concordant couples, those with the highest annual family income showed the greatest gender differences in depressive symptoms. We suggest that family interventions should be gender- and couple-type specific and that mental health counseling is warranted not only for HIV-positive women but also for HIV-negative women in an HIV-affected relationship.

  9. Is the risk of HIV acquisition increased during and immediately after pregnancy? A secondary analysis of pooled HIV community-based studies from the ALPHA network.

    Directory of Open Access Journals (Sweden)

    Milly Marston

    Full Text Available Previous studies of HIV acquisition in pregnancy have been in specific population groups, such as sero-discordant couples which have shown an increased risk of HIV acquisition during pregnancy and studies of sexually active women where the results have been ambiguous. However these studies are unable to tell us what the overall impact of pregnancy is on HIV acquisition in the general population.Data from six community-based HIV cohorts were pooled to give 2,628 sero-conversions and a total of 178,000 person years of observation. Multiple imputation was used to allow for the uncertainty of exact sero-conversion date in surveillance intervals greater than the length of a pregnancy. Results were combined using Rubin's rules to give appropriate error bounds. The analysis was stratified into two periods: pre- and post- widespread availability of prevention of mother-to-child HIV transmission services. This allows us to assess whether there is reporting bias relating to a person's knowledge of their own HIV status which would become more widespread in the latter time period.Results suggest that women while pregnant have a lower risk of acquiring HIV infection over all periods (HRR 0.79, 95%CI 0.70-0.89 than women who were not pregnant. There is no evidence for a difference in the rate of HIV acquisition between postpartum and non-pregnant women (HRR 0.92 95%CI 0.84-1.03.Although there may be immunological reasons for increased risk of HIV acquisition during pregnancy, at a population level this study indicates a lower risk of HIV acquisition for pregnant women. Pregnant women may be more likely to be concordant with their current sexual partner than non-pregnant women, i.e. either already HIV positive prior to the pregnancy or if negative at the time of becoming pregnant more likely to have a negative partner.

  10. Adolescent pre-exposure prophylaxis for HIV prevention: current perspectives

    Science.gov (United States)

    Machado, Daisy Maria; de Sant’Anna Carvalho, Alexandre Machado; Riera, Rachel

    2017-01-01

    Adolescents are a critical population that is disproportionately impacted by the HIV epidemic. More than 2 million adolescents between the age group of 10 and 19 years are living with HIV, and millions are at risk of infection. HIV risks are considerably higher among girls, especially in high-prevalence settings such as eastern and southern Africa. In addition to girls, there are other vulnerable adolescent subgroups, such as teenagers, who use intravenous (IV) drugs, gay and bisexual boys, transgender youth, male sex workers, and people who fall into more than one of these categories. Pre-exposure prophylaxis (PrEP) is a new intervention for people at high risk for acquiring HIV, with an estimated HIV incidence of >3%. Recent data from trials show evidence of the efficacy of PrEP as a powerful HIV prevention tool in high-risk populations, including men who have sex with men, HIV-1-serodiscordant heterosexual couples, and IV drug users. The reported efficacy in those trials of the daily use of oral tenofovir, alone or in combination with emtricitabine, to prevent HIV infection ranged from 44% to 75% and was heavily dependent on adherence. Despite the proven efficacy of PrEP in adult trials, concerns remain about its feasibility in real-life scenarios due to stigma, cost, and limited clinician experience with PrEP delivery. Recent studies are attempting to expand the inquiry into the efficacy of such HIV prophylaxis approaches in adolescent populations, but there are still many gaps in knowledge, and no country has yet approved it for use with adolescents. The aim of this review was to identify and summarize the evidence from studies on PrEP for adolescents. We have compiled and reviewed published studies focusing on safety, feasibility, adherence to therapeutics, self-perception, and legal issues related to PrEP in people aged between 10 and 24 years. PMID:29238237

  11. “I don’t know if this is right…but this is what I’m offering”: Healthcare provider knowledge, practice, and attitudes towards safer conception for HIV-affected couples in the context of Southern African guidelines

    Science.gov (United States)

    Schwartz, Sheree; Phofa, Rebecca; Yende, Nompumelelo; Bassett, Jean; Sanne, Ian; Van Rie, Annelies

    2016-01-01

    The 2011 guidelines for safer conception for HIV-affected individuals and couples were adopted by the South African Department of Health in December 2012. We assessed implementation gaps and facilitators and barriers to delivering safer conception services through examining patient and healthcare provider (HCP) experiences. At Witkoppen Health and Welfare Centre, a primary care clinic in Johannesburg, we conducted in-depth interviews (IDIs) with 9 HCPs (doctors, nurses and counselors) and IDIs and focus group discussions with 42 HIV-affected men and women interested in having a child. Data were analyzed using a grounded theory approach. HCPs were supportive of fertility intentions of HIV-affected couples and demonstrated some knowledge of safer conception methods, especially ART initiation to suppress viral load in infected partners. Unfortunately, HCPs did not follow the key recommendation that HCPs initiate conversations on fertility intentions with HIV-affected men and women. Providers and clients reported that conversations about conception only occur when client-initiated, placing the onus on HIV-affected individuals. Important barriers underlying this were the misconception held by some HCPs that uninfected partners in serodiscordant partnerships are “latently” infected and the desire by most HCPs to protect or control knowledge around fertility and safer conception methods out of concern over what clients will do with this knowledge before they are virally suppressed or ready to conceive. Almost all participants who had conceived or attempted conception did so without safer conception methods knowledge. HCP concern over conception readiness, perception of what clients will do with safer conception knowledge, and gaps in safer conception knowledge prevent HCPs from initiating conversations with HIV-affected patients on the issue of childbearing. Examining these findings in the context of existing South African guidelines illuminates areas that need to be

  12. Number of Psychosocial Strengths Predicts Reduced HIV Sexual Risk Behaviors Above and Beyond Syndemic Problems Among Gay and Bisexual Men.

    Science.gov (United States)

    Hart, Trevor A; Noor, Syed W; Adam, Barry D; Vernon, Julia R G; Brennan, David J; Gardner, Sandra; Husbands, Winston; Myers, Ted

    2017-10-01

    Syndemics research shows the additive effect of psychosocial problems on high-risk sexual behavior among gay and bisexual men (GBM). Psychosocial strengths may predict less engagement in high-risk sexual behavior. In a study of 470 ethnically diverse HIV-negative GBM, regression models were computed using number of syndemic psychosocial problems, number of psychosocial strengths, and serodiscordant condomless anal sex (CAS). The number of syndemic psychosocial problems correlated with serodiscordant CAS (RR = 1.51, 95% CI 1.18-1.92; p = 0.001). When adding the number of psychosocial strengths to the model, the effect of syndemic psychosocial problems became non-significant, but the number of strengths-based factors remained significant (RR = 0.67, 95% CI 0.53-0.86; p = 0.002). Psychosocial strengths may operate additively in the same way as syndemic psychosocial problems, but in the opposite direction. Consistent with theories of resilience, psychosocial strengths may be an important set of variables predicting sexual risk behavior that is largely missing from the current HIV behavioral literature.

  13. Safer sex decision-making among men with haemophilia and HIV and their female partners.

    Science.gov (United States)

    Parish, K L; Cotton, D; Huszti, H C; Parsons, J T

    2001-01-01

    An exploratory qualitative study of adult heterosexual men with haemophilia and HIV and women who were their sexual partners was conducted as formative research to better understand cognitive factors involved in behavioural intentions and practices which comprise HIV risk-reduction for sexual transmission. The study sought to generate hypotheses, uncover themes, and develop a broad perspective on possible determinants of behaviours related to HIV transmission risk reduction. Qualitative analysis of these data served as a basis for developing a subsequent quantitative, hypothesis-testing survey and an intervention. Face-to-face interviews were conducted with 23 single men and 28 married men with haemophilia and HIV infection, and 28 married women partners selected through stratified, purposeful sampling. The interviews identified beliefs, attitudes, and values underlying decisions regarding target behaviours related to preventing sexual transmission of HIV, including (1) using condoms consistently during vaginal intercourse and (2) talking to partners about risk reduction. The interviews elicited information about perceived advantages and disadvantages of performing each of the targeted behaviours, and factors that facilitate or prevent performing them. Qualitative analysis of coded responses yielded important themes regarding how choices are made about sexual activity and safer sex. Most notably, communication between partners (1) plays a direct, key role in facilitating condom use and (2) forms the basis for maintaining emotional intimacy in these relationships. The link between condom use and communicating about safer sex was viewed as pivotal in achieving HIV prevention for individuals in serodiscordant couples. Recommendations for risk reduction intervention development are discussed.

  14. "I don't know if this is right … but this is what I'm offering": healthcare provider knowledge, practice, and attitudes towards safer conception for HIV-affected couples in the context of Southern African guidelines.

    Science.gov (United States)

    West, Nora; Schwartz, Sheree; Phofa, Rebecca; Yende, Nompumelelo; Bassett, Jean; Sanne, Ian; Van Rie, Annelies

    2016-01-01

    The 2011 guidelines for safer conception for HIV-affected individuals and couples were adopted by the South African Department of Health in December 2012. We assessed implementation gaps and facilitators and barriers to delivering safer conception services through examining patient and healthcare provider (HCP) experiences. At Witkoppen Health and Welfare Centre, a primary care clinic in Johannesburg, we conducted in-depth interviews (IDIs) with nine HCPs (doctors, nurses, and counselors) and IDIs and focus group discussions with 42 HIV-affected men and women interested in having a child. Data were analyzed using a grounded theory approach. HCPs were supportive of fertility intentions of HIV-affected couples and demonstrated some knowledge of safer conception methods, especially ART initiation to suppress viral load in infected partners. Unfortunately, HCPs did not follow the key recommendation that HCPs initiate conversations on fertility intentions with HIV-affected men and women. Providers and clients reported that conversations about conception only occur when client-initiated, placing the onus on HIV-affected individuals. Important barriers underlying this were the misconception held by some HCPs that uninfected partners in serodiscordant partnerships are "latently" infected and the desire by most HCPs to protect or control knowledge around fertility and safer conception methods out of concern over what clients will do with this knowledge before they are virally suppressed or ready to conceive. Almost all participants who had conceived or attempted conception did so without safer conception methods knowledge. HCP concern over conception readiness, perception of what clients will do with safer conception knowledge, and gaps in safer conception knowledge prevent HCPs from initiating conversations with HIV-affected patients on the issue of childbearing. Examining these findings in the context of existing South African guidelines illuminates areas that need to be

  15. Sources of Information on HIV and Sexual and Reproductive Health for Couples Living with HIV in Rural Southern Malawi

    Directory of Open Access Journals (Sweden)

    Belinda Chimphamba Gombachika

    2013-01-01

    Full Text Available With wider access to antiretroviral therapy, people living with HIV are reconsidering their reproductive decisions: remarrying and having children. The purpose of the paper is to explore sources of information for reproductive decision used by couples living with HIV in patrilineal and matrilineal districts of Malawi. Data were collected from forty couples from July to December 2010. Our results illuminate five specific issues: some of the informants (1 remarry after divorce/death of a spouse, (2 establish new marriage relationship with spouses living with HIV, and (3 have children hence the need for information to base their decisions. There are (4 shared and interactive couple decisions, and (5 informal networks of people living with HIV are the main sources of information. In addition, in matrilineal community, cultural practices about remarriage set up structures that constrained information availability unlike in patrilineal community where information on sexual and reproductive health, HIV, and AIDS was disseminated during remarriage counselling. However, both sources are not able to provide comprehensive information due to complexity and lack of up to date information. Therefore, health workers should, offer people living with HIV comprehensive information that takes into consideration the cultural specificity of groups, and empower already existing and accepted local structures with sexual and reproductive health, HIV, and AIDS knowledge.

  16. A Group Intervention for HIV/STI Risk Reduction among Indian Couples

    Directory of Open Access Journals (Sweden)

    Ritu Nehra

    2013-12-01

    Full Text Available Background: HIV in India is transmitted primarily by heterosexual contact. The present study sought to test the feasibility of a group HIV/STI risk reduction intervention among heterosexual couples in India. Methods: Focus groups and key informant interviews were used in 2008 to culturally tailor the intervention. Thirty sexually active and HIV/STI negative couples were enrolled and assessed regarding risk behavior and sexual barrier acceptability. Gender-concordant group sessions used cognitive behavioral strategies for HIV/STI prevention. Results: At baseline, male condom use was low (36%; no participants reported use of female condoms or vaginal gels. HIV knowledge was low; women had more HIV knowledge and more positive attitudes towards condom use than men. Post-intervention, willingness to use all barrier products (t = 10.0, P< .001 and intentions to avoid risk behavior increased (t = 5.62, P< .001. Conclusion: This study illustrates the feasibility of utilizing a group intervention to enhance HIV/STI risk reduction among Indian couples.

  17. How Best to Obtain Valid, Verifiable Data Online From Male Couples? Lessons Learned From an eHealth HIV Prevention Intervention for HIV-Negative Male Couples.

    Science.gov (United States)

    Mitchell, Jason; Lee, Ji-Young; Stephenson, Rob

    2016-09-20

    As interest increases in the development of eHealth human immunodeficiency virus (HIV)-preventive interventions for gay male couples, Web-based methods must also be developed to help increase the likelihood that couples enrolled and data collected from them represent true unique dyads. Methods to recruit and collect reliable and valid data from both members of a couple are lacking, yet are crucial for uptake of novel sexual health and HIV-prevention eHealth interventions. Methods to describe best practices to recruit male couples using targeted advertisements on Facebook are also lacking in the literature, yet could also help in this uptake. The objective of our study was to describe challenges and lessons learned from experiences from two phases (developmental phase and online randomized controlled trial [RCT]) of an eHealth HIV-prevention intervention for concordant HIV-negative male couples in terms of (1) recruiting male couples using targeted advertisements on Facebook, (2) validating that data came from two partners of the couple, and (3) verifying that the two partners of the couple are in a relationship with each other. The developmental phase refined the intervention via in-person focus groups, whereas the pilot-testing phase included an online RCT. For both phases, couples were recruited via targeted Facebook advertisements. Advertisements directed men to a study webpage and screener; once eligible, participants provided consent electronically. A partner referral system was embedded in the consenting process to recruit the relationship partner of the participant. Both men of the couple had to meet all eligibility criteria-individually and as a couple-before they could enroll in the study. Verification of couples' relationships was assessed via the concurrence of predetermined screener items from both partners, done manually in the developmental phase and electronically in the pilot-testing phase. A system of decision rules was developed to assess the

  18. Effectiveness of semen washing to prevent human immunodeficiency virus (HIV) transmission and assist pregnancy in HIV-discordant couples: a systematic review and meta-analysis.

    Science.gov (United States)

    Zafer, Maryam; Horvath, Hacsi; Mmeje, Okeoma; van der Poel, Sheryl; Semprini, Augusto E; Rutherford, George; Brown, Joelle

    2016-03-01

    To evaluate the effectiveness of semen washing in human immunodeficiency virus (HIV)-discordant couples in which the male partner is infected. Systematic review and meta-analysis. Not applicable. Forty single-arm open-label studies among HIV-discordant couples that underwent intrauterine insemination (IUI) or in vitro fertilization (IVF) with or without intracytoplasmic sperm injection (ICSI) using washed semen. Semen washing followed by IUI, IVF, or IVF/ICSI. HIV transmission to HIV-uninfected women; secondary outcomes: HIV transmission to newborns and proportion of couples achieving a clinical pregnancy. No HIV transmission occurred in 11,585 cycles of assisted reproduction with the use of washed semen among 3,994 women. Among the subset of HIV-infected men without plasma viral suppression at the time of semen washing, no HIV seroconversions occurred among 1,023 women after 2,863 cycles of assisted reproduction with the use of washed semen. Studies that measured HIV transmission to infants reported no cases of vertical transmission. Overall, 56.3% of couples (2,357/4,184) achieved a clinical pregnancy with the use of washed semen. Semen washing appears to significantly reduce the risk of transmission in HIV-discordant couples desiring children, regardless of viral suppression in the male partner. There are no randomized controlled studies or studies from low-income countries, especially those with a large burden of HIV. Continued development of lower-cost semen washing and assisted reproduction technologies is needed. Integration of semen washing into HIV prevention interventions could help to further reduce the spread of HIV. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  19. Management of Infertility in HIV infected couples: A Review ...

    African Journals Online (AJOL)

    for fertility services in the HIV-positive population has thus increased and may be employed for management of infertility and protection from transmission or acquisition of HIV infection. As such, preconception counseling, sexual health and fertility screening have become routine in the management of HIV-positive couples.

  20. “The More Support You Have the Better”: Partner Support and Dyadic HIV Care Across the Continuum for Gay and Bisexual Men

    Science.gov (United States)

    Goldenberg, Tamar; Stephenson, Rob

    2015-01-01

    Background Gay, bisexual, and other men who have sex with men account for a disproportionate burden of HIV incidence in the United States, with one-third to two-thirds of these new HIV infections occurring within main partnerships. Early initiation and adherence to highly active antiretroviral treatment is a key factor in treating and preventing the transmission of HIV; however, the average rate of adherence in the United States is low. Social support has been examined as a source of improving health for people experiencing a variety of chronic health conditions. This study aims to understand perceptions of how dyadic HIV care could influence partner-specific support for same-sex male couples with a goal of improving adherence. Methods Data were collected from 5 focus group (n = 35) discussions with gay and bisexual men in same-sex male relationships in Atlanta, GA. Participants discussed perceptions of how dyadic HIV care would impact partner support among serodiscordant and seroconcordant HIV-positive same-sex male couples. Verbatim transcripts were segmented thematically and systematically analyzed to examine patterns. Results Participants described how dyadic HIV care can facilitate emotional, informational, and instrumental support at various stages across the continuum of care, depending on partner dynamics. Participants stated that dyadic HIV care can provide an additional “sense of togetherness” and “solidarity” that helps to “alleviate stress.” Conclusions Results suggest that dyadic approaches for HIV care across the continuum may be useful in promoting partner support and improving adherence. Future research should further examine dyadic interventions for HIV treatment among same-sex male couples. PMID:25867781

  1. Determinants in HIV counselling and testing in couples in North Rift Kenya.

    Science.gov (United States)

    Ayuo, P O; Were, E; Wools-Kaloustian, K; Baliddawa, J; Sidle, J; Fife, K

    2009-02-01

    Voluntary HIV counselling and testing (VCT) has been shown to be an acceptable and effective tool in the fight against HIV/AIDS. Couple HIV Counselling and Testing (CHCT) however, is a relatively new concept whose acceptance and efficacy is yet to be determined. To describe factors that motivate couples to attend VCT as a couple. A cross sectional qualitative study. Moi Teaching and Referral Hospital and Moi University, School of Medicine, Eldoret, Kenya Seventy one individuals were interviewed during KII (9) and dyad interviews (31 couples). Ten FGDs involving a total of 109 individuals were held. Cultural practices, lack of CHCT awareness, stigma and fear of results deter CHCT utilisation. Location of centre where it is unlikely to be associated with HIV testing, qualified professional staff and minimal waiting times would enhance CHCT utilisation. CHCT as a tool in the fight against HIV/AIDS in this region of Kenya is feasible as the factors that would deter couples are not insurmountable.

  2. Bacterial vaginosis associated with increased risk of female-to-male HIV-1 transmission: a prospective cohort analysis among African couples.

    Directory of Open Access Journals (Sweden)

    Craig R Cohen

    -1 transmission to male partners. Several limitations may affect the generalizability of our results including: all participants underwent couples HIV counseling and testing and enrolled in an HIV-1 prevention trial, and index participants had a baseline CD4 count ≥ 250 cells/mm³ and were HSV-2 seropositive. Given the high prevalence of BV and the association of BV with increased risk of both female HIV-1 acquisition and transmission found in our study, if this association proves to be causal, BV could be responsible for a substantial proportion of new HIV-1 infections in Africa. Normalization of vaginal flora in HIV-1-infected women could mitigate female-to-male HIV-1 transmission.ClinicalTrials.com NCT00194519.

  3. Smoking, internalized heterosexism, and HIV disease management among male couples.

    Science.gov (United States)

    Gamarel, K E; Neilands, T B; Dilworth, S E; Taylor, J M; Johnson, M O

    2015-01-01

    High rates of cigarette smoking have been observed among HIV-positive individuals. Smoking has been linked to HIV-related medical complications and non-AIDS defining cancers and negatively impacts on immune function and virologic control. Although internalized heterosexism has been related to smoking behaviors, little is known about associations between partners' reports of smoking, internalized heterosexism, and HIV medication management in male couples with HIV. A sample of 266 male couples completed baseline assessments for a cohort study examining relationship factors and HIV treatment. A computer-based survey assessed self-reported smoking behaviors, alcohol use, internalized heterosexism, and antiretroviral therapy (ART) adherence. HIV-positive men also provided blood samples to assess viral load. Approximately 30% of the sample reported that they are currently smoking cigarettes. After adjusting for demographic characteristics, men in a primary relationship with a partner who reported currently smoking had more than five-fold greater odds of reporting smoking. Higher levels of internalized heterosexism and financial hardship were each independently associated with greater odds of reporting smoking. Among HIV-positive men on ART (n = 371), having a partner who reported smoking was associated with almost three-fold greater odds of having a detectable viral load. Our findings add new support to the evidence of romantic partners influencing each other's health behaviors, and demonstrate an association between smoking and disease management within male couples. Future research should explore the interpersonal and social contexts of smoking in order to develop interventions that meet the unique needs of male couples.

  4. Differences in Gay Male Couples' Use of Drugs and Alcohol With Sex by Relationship HIV Status.

    Science.gov (United States)

    Mitchell, Jason W

    2016-07-01

    Prior studies with men who have sex with men have documented a strong association between substance use with sex and risk for acquisition of HIV. However, few studies have been conducted about gay male couples' use of substances with sex, despite the fact that between one third and two thirds of men who have sex with men acquire HIV from their relationship partners. The present study sought to (1) describe whether one or both partners in the male couple uses substances with sex-by substance type-within and/or outside of their relationship, and (2) assess whether differences exist in those who use substances with sex within and outside the relationship by the couples' HIV status. Dyadic data for this analysis were collected in the United States from a nation-wide cross-sectional Internet study about male couples' relationships and behaviors. Couple-level descriptive and comparative analyses were employed with 361 male couples. Except for alcohol, most couples did not use substances with sex. Of those who did, rates of who used it with sex and substance type within the relationship varied; most couples only had one partner who used substances with sex outside the relationship. Significantly higher proportions of concordantly HIV-negative and HIV-positive couples had both partners who used substances (all types) with sex within their relationship over discordant couples. Most couples had one partner who used outside the relationship; only marijuana and erectile dysfunction medication use with sex significantly differed by couples' HIV status. Findings indicate the need to conduct additional research for prevention development. © The Author(s) 2014.

  5. Contraceptive options for women living with HIV.

    Science.gov (United States)

    Phillips, Sharon; Steyn, Petrus; Temmerman, Marleen

    2014-08-01

    Women living with HIV are often of reproductive age, and many desire effective contraceptive options to delay or prevent pregnancy. We review the safety of various hormonal and non-hormonal contraceptive methods for women living with human immunodeficiency virus (HIV). Additionally, we discuss drug interactions between contraceptive methods and antiretrovirals and the safety of methods with respect to onward transmission to HIV-negative partners for women in sero-discordant partnerships. In general, most methods are safe for most women living with HIV. An understanding of the reproductive goals of each individual patient, as well as her medical condition and medication, should be taken into account when counselling women on their contraceptive options. Further research is needed to understand drug interactions between contraceptives and antiretrovirals better and how to fulfil the contraceptive needs of HIV-positive women. Copyright © 2014. Published by Elsevier Ltd.

  6. Gender inequality and the risk of HIV among married couples in North India.

    Science.gov (United States)

    Bloom, Shelah S; Agrawal, Alpna; Singh, Kaushalendra K; Suchindran, Chirayath M

    2015-01-01

    This study investigated the distribution and determinants of HIV risks among married couples in North India. Gender inequality emerged as a potential driver of HIV risks in this region. Data collection took place in 2003 in a probability survey of 3385 couples living in India's most populous state - Uttar Pradesh - and Uttaranchal. Couples' analyses utilizing generalized estimating equations showed that compared with husbands, wives were less knowledgeable about HIV (OR = 0.31, 95% CI = 0.27-0.36), more likely to consider themselves at risk for infection (OR = 6.86, 95% CI = 4.65-10.13), and less likely to feel that a wife had the right to refuse sex with her husband (OR = 0.50, 95% CI = 0.44-0.58). The proportion of husbands reporting non-marital sex in the past year was 7.1% and transactional sex in the past year, 2.2%. Among their wives, 73.4% were unaware of their husbands' non-marital sexual behaviors and only 28.9% of husbands reported condom use during their last non-marital sexual encounter. Logistic regression analyses showed that husbands' alcohol use, husbands' mobility, and urban residence were positively associated with husbands' non-marital sexual behaviors adjusting for other covariates. The data demonstrate that HIV prevention programs among couples in North India should consider both sexual risks and gender inequalities which potentially fuel HIV spread in this region.

  7. Gender Differences in Depressive Symptoms Among HIV-Positive Concordant and Discordant Heterosexual Couples in China

    OpenAIRE

    Li, Li; Liang, Li-Jung; Lin, Chunqing; Ji, Guoping; Xiao, Yongkang

    2016-01-01

    HIV seropositive individuals and their heterosexual partners/spouses, either seropositive or seronegative, are facing several mental health challenges. The objective of this study was to examine gender differences in depressive symptoms among HIV-positive concordant and HIV-discordant couples. We identified heterosexual couples from participants of a randomized controlled trial conducted in Anhui province, China. A total of 265 couples, comprising 129 HIV+ male/HIV− female couples, 98 HIV− ma...

  8. HIV-infected presumptive tuberculosis patients without tuberculosis: How many are eligible for antiretroviral therapy in Karnataka, India?

    Directory of Open Access Journals (Sweden)

    Ajay M.V. Kumar

    2017-03-01

    Full Text Available For certain subgroups within people living with the human immunodeficiency virus (HIV [active tuberculosis (TB, pregnant women, children <5 years old, and serodiscordant couples], the World Health Organization recommends antiretroviral therapy (ART irrespective of CD4 count. Another subgroup which has received increased attention is “HIV-infected presumptive TB patients without TB”. In this study, we assess the proportion of HIV-infected presumptive TB patients eligible for ART in Karnataka State (population 60 million, India. This was a cross-sectional analysis of data of HIV-infected presumptive TB patients diagnosed in May 2015 abstracted from national TB and HIV program records. Of 42,585 presumptive TB patients, 28,964 (68% were tested for HIV and 2262 (8% were HIV positive. Of the latter, 377 (17% had active TB. Of 1885 “presumptive TB patients without active TB”, 1100 (58% were already receiving ART. Of the remaining 785 who were not receiving ART, 617 (79% were assessed for ART eligibility and of those, 548 (89% were eligible for ART. About 90% of “HIV-infected presumptive TB patients without TB” were eligible for ART. This evidence supports a public health approach of starting all “HIV-infected presumptive TB patients without TB” on ART irrespective of CD4 count in line with global thinking about ‘test and treat’.

  9. Risk Factor Associated with Negative Spouse HIV Seroconversion among Sero-Different Couples: A Nested Case-Control Retrospective Survey Study in 30 Counties in Rural China.

    Directory of Open Access Journals (Sweden)

    Houlin Tang

    Full Text Available Antiretroviral therapy (ART and condom use have been proven to reduce the risk of sexual transmission of human immunodeficiency virus (HIV among HIV sero-different couples, but its full implementation remains a challenge. This study aims to assess HIV seroconversion rate of HIV-negative spouse and its associated risk factors among HIV sero-different couples in rural China.An open cohort of HIV sero-different couples enrolled in 30 counties in China between October 1, 2010, and September 30, 2012, and followed-up to December 31, 2012, was constructed retrospectively. A nested case-control study of risk factors of HIV seroconversion among sero-different couples was conducted in April and May of 2013, based on the open cohort. Sero-different couples with the HIV-negative spouse seroconverting at least 3 months after the previous negative diagnosis during cohort observation period were labeled as "case couples". The "control couples" were selected randomly from the same cohort that did not have the HIV-negative spouse seroconversion during the same period. The "case couples" and "control couples" were matched on gender, age, and region of residence. Sexual behaviors among HIV sero-different couples before and after the index spouses notifying their HIV infection status to their HIV-negative spouses were collected via face-to-face interview. Univariate and multivariate logistic regression models were used to assess factors associated with HIV seroconversion among HIV sero-different couples.Of 4481 HIV sero-different couples, a total of 53 seroconversions were observed within 5218 person-years of follow-up. The incidence rate was 1.02 (95%CI: 0.76-1.33 per 100 person-years. Forty "case couples" confirmed HIV-negative spouse seroconversions infected via marital sexual transmission, were matched to 80 "control couples". Of the 120 couples, 81(67.5% were receiving ART, and 70 (58.3% reported consistently used condoms during intercourse after the index

  10. Risk Factor Associated with Negative Spouse HIV Seroconversion among Sero-Different Couples: A Nested Case-Control Retrospective Survey Study in 30 Counties in Rural China.

    Science.gov (United States)

    Tang, Houlin; Wu, Zunyou; Mao, Yurong; Cepeda, Javier; Morano, Jamie

    2016-01-01

    Antiretroviral therapy (ART) and condom use have been proven to reduce the risk of sexual transmission of human immunodeficiency virus (HIV) among HIV sero-different couples, but its full implementation remains a challenge. This study aims to assess HIV seroconversion rate of HIV-negative spouse and its associated risk factors among HIV sero-different couples in rural China. An open cohort of HIV sero-different couples enrolled in 30 counties in China between October 1, 2010, and September 30, 2012, and followed-up to December 31, 2012, was constructed retrospectively. A nested case-control study of risk factors of HIV seroconversion among sero-different couples was conducted in April and May of 2013, based on the open cohort. Sero-different couples with the HIV-negative spouse seroconverting at least 3 months after the previous negative diagnosis during cohort observation period were labeled as "case couples". The "control couples" were selected randomly from the same cohort that did not have the HIV-negative spouse seroconversion during the same period. The "case couples" and "control couples" were matched on gender, age, and region of residence. Sexual behaviors among HIV sero-different couples before and after the index spouses notifying their HIV infection status to their HIV-negative spouses were collected via face-to-face interview. Univariate and multivariate logistic regression models were used to assess factors associated with HIV seroconversion among HIV sero-different couples. Of 4481 HIV sero-different couples, a total of 53 seroconversions were observed within 5218 person-years of follow-up. The incidence rate was 1.02 (95%CI: 0.76-1.33) per 100 person-years. Forty "case couples" confirmed HIV-negative spouse seroconversions infected via marital sexual transmission, were matched to 80 "control couples". Of the 120 couples, 81(67.5%) were receiving ART, and 70 (58.3%) reported consistently used condoms during intercourse after the index spouse was

  11. Contexts of vulnerability and the acceptability of new biomedical HIV prevention technologies among key populations in South Africa: A qualitative study.

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    Millicent Atujuna

    Full Text Available New biomedical prevention technologies (NPTs may contribute to substantially reducing incident HIV infections globally. We explored acceptability and preferences for NPTs among key and other vulnerable populations in two South African townships.We conducted six focus groups and 12 in-depth interviews with adolescents, and adult heterosexual men, women, and men who have sex with men (MSM (n = 48, and eight in-depth interviews with key informant healthcare workers. The interview guide described pre-exposure prophylaxis (PrEP, vaginal rings, rectal microbicides and HIV vaccines, and explored acceptability and product preferences. Focus groups and in-depth interviews (45-80 minutes were conducted in Xhosa, audiotaped, and transcribed and translated into English. Data were coded and reviewed using framework analysis with NVivo software.Overall, initial enthusiasm and willingness to use NPTs evolved into concerns about how particular NPTs might affect or require alterations in one's everyday lifestyle and practices. Different product preferences and motivations emerged by population based on similarity to existing practices and contexts of vulnerability. Adult women and female adolescents preferred a vaginal ring and HIV vaccine, motivated by longer duration of protection to mitigate feared repercussions from male partners, including threats to their marriage and safety, and a context of ubiquitous rape. Male adolescents preferred an HIV vaccine, seen as protection in serodiscordant relationships and convenient in obviating the HIV stigma and cost involved in buying condoms. Adult men preferred PrEP, given familiarity with oral medications and mistrust of injections, seen as enabling serodiscordant couples to have a child. MSM preferred a rectal microbicide given familiarity with gel-based lubricants, with concerns about duration of protection in the context of unplanned consensual sex and rape.Biomedical interventions to prevent HIV transmission

  12. Contexts of vulnerability and the acceptability of new biomedical HIV prevention technologies among key populations in South Africa: A qualitative study.

    Science.gov (United States)

    Atujuna, Millicent; Newman, Peter A; Wallace, Melissa; Eluhu, Megan; Rubincam, Clara; Brown, Ben; Bekker, Linda-Gail

    2018-01-01

    New biomedical prevention technologies (NPTs) may contribute to substantially reducing incident HIV infections globally. We explored acceptability and preferences for NPTs among key and other vulnerable populations in two South African townships. We conducted six focus groups and 12 in-depth interviews with adolescents, and adult heterosexual men, women, and men who have sex with men (MSM) (n = 48), and eight in-depth interviews with key informant healthcare workers. The interview guide described pre-exposure prophylaxis (PrEP), vaginal rings, rectal microbicides and HIV vaccines, and explored acceptability and product preferences. Focus groups and in-depth interviews (45-80 minutes) were conducted in Xhosa, audiotaped, and transcribed and translated into English. Data were coded and reviewed using framework analysis with NVivo software. Overall, initial enthusiasm and willingness to use NPTs evolved into concerns about how particular NPTs might affect or require alterations in one's everyday lifestyle and practices. Different product preferences and motivations emerged by population based on similarity to existing practices and contexts of vulnerability. Adult women and female adolescents preferred a vaginal ring and HIV vaccine, motivated by longer duration of protection to mitigate feared repercussions from male partners, including threats to their marriage and safety, and a context of ubiquitous rape. Male adolescents preferred an HIV vaccine, seen as protection in serodiscordant relationships and convenient in obviating the HIV stigma and cost involved in buying condoms. Adult men preferred PrEP, given familiarity with oral medications and mistrust of injections, seen as enabling serodiscordant couples to have a child. MSM preferred a rectal microbicide given familiarity with gel-based lubricants, with concerns about duration of protection in the context of unplanned consensual sex and rape. Biomedical interventions to prevent HIV transmission, rather than

  13. Case series of fertility treatment in HIV-discordant couples (male positive, female negative: the Ontario experience.

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    Trent Newmeyer

    Full Text Available The success of combination antiretroviral therapies for the treatment of human immunodeficiency virus (HIV has resulted in prolonged life expectancy (over 40 years from diagnosis and an improved quality of life for people living with HIV. The risk of vertical HIV transmission during pregnancy has been reduced to less than 1%. As a result of these breakthroughs and as many of these individuals are of reproductive age, fertility issues are becoming increasingly important for this population. One population in which conception planning and reduction of horizontal HIV transmission warrants further research is HIV-discordant couples where the male partner is HIV-positive and the female partner is HIV-negative. Sperm washing is a technique carried out in a fertility clinic that separates HIV from the seminal fluid. Although sperm washing followed by intrauterine insemination significantly reduces the risk of horizontal HIV transmission, there has been limited access to the procedure in North America. Furthermore, little is known about the conception decision-making experiences of HIV-discordant couples who might benefit from sperm washing. Chart reviews and semi-structured interviews were completed with 12 HIV-discordant couples in Ontario, Canada. Couples were recruited through HIV clinics and one fertility clinic that offered sperm washing. Participants identified a number of factors that affected their decision-making around pregnancy planning. Access to sperm washing and other fertility services was an issue (cost, travel and few clinics. Participants identified a lack of information on the procedure (availability, safety. Sources of support (social networks, healthcare providers were unevenly distributed, especially among those who did not disclose their HIV status to friends and family. Finally, the stigmatisation of HIV continues to have a negative affect on HIV-discordant couples and their intentions to conceive. Access to sperm washing and

  14. Outcomes of Assisted Reproductive Techniques for HIV-1-discordant Couples Using Thawed Washed Sperm in Taiwan: Comparison With Control and Testicular Sperm Extraction/Microscopic Epididymal Sperm Aspiration Groups

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    Ming-Yih Wu

    2011-08-01

    Conclusion: The preliminary data showed good ART results in HIV-1-discordant couples. Fertility services should not be withheld from individuals with HIV-1, although larger series are needed to reach conclusions about safety.

  15. Can the Catholic Church agree to condom use by HIV-discordant couples?

    Science.gov (United States)

    Bovens, L

    2009-12-01

    Does the position of the Roman Catholic Church on contraception also imply that the usage of condoms by HIV-discordant couples is illicit? A standard argument is to appeal to the doctrine of double effect to condone such usage, but this meets with the objection that there exists an alternative action that brings about the good effect-namely, abstinence. I argue against this objection, because an HIV-discordant couple does not bring about any bad outcome through condom usage-there is no disrespect displayed for the generative function of sex. One might retort that the badness of condom usage consists in thwarting the unitive function of sex. I argue that also this objection cannot be upheld. In conclusion, if there are no in-principle objections against condom usage for HIV-discordant couples, then policies that deny access to condoms to such couples are indefensible. HIV-discordant couples have a right to continue consummating their marriage in a manner that is minimally risky and this right cannot be trumped by utilitarian concerns that the distribution of condoms might increase promiscuity and along with it the HIV infection rate.

  16. Developing a Video-Based eHealth Intervention for HIV-Positive Gay, Bisexual, and Other Men Who Have Sex with Men: Study Protocol for a Randomized Controlled Trial.

    Science.gov (United States)

    Hirshfield, Sabina; Downing, Martin J; Parsons, Jeffrey T; Grov, Christian; Gordon, Rachel J; Houang, Steven T; Scheinmann, Roberta; Sullivan, Patrick S; Yoon, Irene S; Anderson, Ian; Chiasson, Mary Ann

    2016-06-17

    Gay, bisexual, and other men who have sex with men (GBMSM) accounted for 67% of new US human immunodeficiency virus (HIV) infections in 2012; however, less than 40% of HIV-positive GBMSM are virally suppressed. Preventing transmission from virally unsuppressed men who have condomless anal sex (CAS) with serodiscordant partners is a public health imperative. New HIV infections in GBMSM are attributed in part to online access to sex partners; therefore, low-cost eHealth interventions are a unique opportunity to reach men where they meet partners. To describe the protocol of a randomized controlled trial evaluating whether video-based messaging delivered online may lead to reductions in serodiscordant CAS and increased HIV disclosure. Sex Positive!([+]) is a two-arm, phase III, video-based randomized controlled trial delivered online to GBMSM living with HIV. Participants in the intervention arm receive 10 video vignettes grounded in social learning and social cognitive theories that are designed to elicit critical thinking around issues of HIV transmission and disclosure. Participants in the attention control arm receive 10 video vignettes that focus on healthy living. All videos are optimized for mobile viewing. The study protocol includes five online assessments conducted over a 1-year period among 1500 US white, black, or Hispanic/Latino GBMSM living with HIV who report suboptimal antiretroviral therapy (ART) adherence or a detectable viral load in the past 12 months and recent CAS (past 6 months) with HIV-negative or unknown status male partners. Compared to the control arm, we hypothesize that men who watch the intervention videos will report at 12-month follow-up significantly fewer serodiscordant CAS partners, increased HIV disclosure, and improved social cognition (eg, condom use self-efficacy, perceived responsibility). Participant recruitment began in June 2015 and ended in December 2015. This protocol describes the underlying theoretical framework and

  17. 'Testing Together Challenges the Relationship': Consequences of HIV Testing as a Couple in a High HIV Prevalence Setting in Rural South Africa.

    Directory of Open Access Journals (Sweden)

    Hanani Tabana

    Full Text Available We conducted qualitative individual and combined interviews with couples to explore their experiences since the time of taking an HIV test and receiving the test result together, as part of a home-based HIV counselling and testing intervention.This study was conducted in October 2011 in rural KwaZulu-Natal, South Africa, about 2 years after couples tested and received results together. Fourteen couples were purposively sampled: discordant, concordant negative and concordant positive couples.Learning about each other's status together challenged relationships of the couples in different ways depending on HIV status and gender. The mutual information confirmed suspected infidelity that had not been discussed before. Negative women in discordant partnerships remained with their positive partner due to social pressure and struggled to maintain their HIV negative status. Most of the couple relationships were characterized by silence and mistrust. Knowledge of sero-status also led to loss of sexual intimacy in some couples especially the discordant. For most men in concordant negative couples, knowledge of status was an awakening of the importance of fidelity and an opportunity for behaviour change, while for concordant positive and discordant couples, it was seen as proof of infidelity. Although positive HIV status was perceived as confirmation of infidelity, couples continued their relationship and offered some support for each other, living and managing life together. Sexual life in these couples was characterized by conflict and sometimes violence. In the concordant negative couples, trust was enhanced and behaviour change was promised.Findings suggest that testing together as couples challenged relationships in both negative and positive ways. Further, knowledge of HIV status indicated potential to influence behaviour change especially among concordant negatives. In the discordant and concordant positive couples, traditional gender roles exposed

  18. Canadian HIV Pregnancy Planning Guidelines: No. 278, June 2012.

    Science.gov (United States)

    Loutfy, Mona R; Margolese, Shari; Money, Deborah M; Gysler, Mathias; Hamilton, Scot; Yudin, Mark H

    2012-10-01

    Four main clinical issues need to be considered for HIV-positive individuals and couples with respect to pregnancy planning and counselling: (1) pre-conceptional health; (2) transmission from mother to infant, which has been significantly reduced by combined antiretroviral therapy; (3) transmission between partners during conception, which requires different prevention and treatment strategies depending on the status and needs of those involved; and (4) management of infertility issues. The objective of the Canadian HIV Pregnancy Planning Guidelines is to provide clinical information and recommendations for health care providers to assist HIV-positive individuals and couples with their fertility and pregnancy planning decisions. These guidelines are evidence- and community-based and flexible, and they take into account diverse and intersecting local/population needs and the social determinants of health. Intended outcomes are (1) reduction of risk of vertical transmission and horizontal transmission of HIV, (2) improvement of maternal and infant health outcomes in the presence of HIV, (3) reduction of the stigma associated with pregnancy and HIV, and (4) increased access to pregnancy planning and fertility services. PubMed and Medline were searched for articles published in English or French to December 20, 2010, using the following terms: "HIV" and "pregnancy" or "pregnancy planning" or "fertility" or "reproduction" or "infertility" or "parenthood" or "insemination" or "artificial insemination" or "sperm washing" or "IVF" or "ICSI" or "IUI." Other search terms included "HIV" and 'horizontal transmission" or "sexual transmission" or "serodiscordant." The following conference databases were also searched: Conference on Retroviruses and Opportunistic Infections, International AIDS Conference, International AIDS Society, Interscience Conference on Antimicrobial Agents and Chemotherapy, the Canadian Association of HIV/AIDS Research, and the Ontario HIV Treatment

  19. Home-Based HIV Testing and Counseling for Male Couples (Project Nexus): A Protocol for a Randomized Controlled Trial.

    Science.gov (United States)

    Stephenson, Rob; Freeland, Ryan; Sullivan, Stephen P; Riley, Erin; Johnson, Brent A; Mitchell, Jason; McFarland, Deborah; Sullivan, Patrick S

    2017-05-30

    HIV prevalence remains high among men who have sex with men (MSM) in the United States, yet the majority of research has focused on MSM as individuals, not as dyads, and has discussed HIV risks primarily in the context of casual sex. Nexus is an online prevention program that combines home-based HIV testing and couples HIV testing and counseling (CHTC). It allows partners in dyadic MSM relationships to receive HIV testing and care in the comfort of their designated residence, via video-based chat. By using video-based technologies (eg, VSee video chat), male couples receive counseling and support from a remote online counselor, while testing for HIV at home. This randomized control trial (RCT) aims to examine the effects of video-based counseling combined with home-based HIV testing on couples' management of HIV risk, formation and adherence to explicit sexual agreements, and sexual risk-taking. The research implements a prospective RCT of 400 online-recruited male couples: 200 self-reported concordant-negative couples and 200 self-reported discordant couples. Couples in the control arm will receive one or two home-based HIV self-testing kits and will be asked to report their results via the study's website. Couples in the experimental arm will receive one or two home-based HIV self-testing kits and will conduct these tests together under the facilitation of a remotely located counselor during a prescheduled VSee-based video CHTC session. Study assessments are taken at baseline, as well as at 3- and 6-month follow-up sessions. Project Nexus was launched in April 2016 and is ongoing. To date, 219 eligible couples have been enrolled and randomized. Combining home-based HIV testing with video-based counseling creates an opportunity to expand CHTC to male couples who (1) live outside metro areas, (2) live in rural areas without access to testing services or LGBTQ resources, or (3) feel that current clinic-based testing is not for them (eg, due to fears of

  20. The Impact of Couple HIV Testing and Counseling on Consistent Condom Use Among Pregnant Women and Their Male Partners: An Observational Study.

    Science.gov (United States)

    Rosenberg, Nora E; Graybill, Lauren A; Wesevich, Austin; McGrath, Nuala; Golin, Carol E; Maman, Suzanne; Bhushan, Nivedita; Tsidya, Mercy; Chimndozi, Limbikani; Hoffman, Irving F; Hosseinipour, Mina C; Miller, William C

    2017-08-01

    In sub-Saharan Africa couple HIV testing and counseling (CHTC) has been associated with substantial increases in safe sex, especially when at least one partner is HIV infected. However, this relationship has not been characterized in an Option B+ context. The study was conducted at the antenatal clinic at Bwaila District Hospital in Lilongwe, Malawi in 2016 under an Option B+ program. Ninety heterosexual couples with an HIV-infected pregnant woman (female-positive couples) and 47 couples with an HIV-uninfected pregnant woman (female-negative couples) were enrolled in an observational study. Each couple member was assessed immediately before and 1 month after CHTC for safe sex (abstinence or consistent condom use in the last month). Generalized estimating equations were used to model change in safe sex before and after CHTC and to compare safe sex between female-positive and female-negative couples. Mean age was 26 years among women and 32 years among men. Before CHTC, safe sex was comparable among female-positive couples (8%) and female-negative couples (2%) [risk ratio (RR): 3.7, 95% confidence interval (CI): 0.5 to 29.8]. One month after CHTC, safe sex was higher among female-positive couples (75%) than among female-negative couples (3%) (RR: 30.0, 95% CI: 4.3 to 207.7). Safe sex increased substantially after CTHC for female-positive couples (RR 9.6, 95% CI: 4.6 to 20.0), but not for female-negative couples (RR: 1.2, 95% CI: 0.1 to 18.7). Engaging pregnant couples in CHTC can have prevention benefits for couples with an HIV-infected pregnant woman, but additional prevention approaches may be needed for couples with an HIV-uninfected pregnant woman.

  1. Current perspectives in HIV post-exposure prophylaxis

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    Sultan B

    2014-10-01

    Full Text Available Binta Sultan,1,2 Paul Benn,1 Laura Waters1 1Department of Genitourinary Medicine, Mortimer Market Centre, Central and North West London NHS Foundation Trust, London, UK; 2Centre for Sexual Health and HIV Research, University College London, London, UK Abstract: The incidence of human immunodeficiency virus (HIV infection continues to rise among core groups and efforts to reduce the numbers of new infections are being redoubled. Post-exposure prophylaxis (PEP is the use of short-term antiretroviral therapy (ART to reduce the risk of acquisition of HIV infection following exposure. Current guidelines recommend a 28-day course of ART within 36–72 hours of exposure to HIV. As long as individuals continue to be exposed to HIV there will be a role for PEP in the foreseeable future. Nonoccupational PEP, the vast majority of which is for sexual exposure (PEPSE, has a significant role to play in HIV prevention efforts. Awareness of PEP and its availability for both clinicians and those who are eligible to receive it are crucial to ensure that PEP is used to its full potential in any HIV prevention strategy. In this review, we provide current evidence for the use of PEPSE, assessment of the risk of HIV transmission, indications for PEP, drug regimens, and management of patients started on PEP. We summarize national and international guidelines for the use of PEPSE. We explore the place of PEP within the wider strategy of reducing HIV incidence rates in the era of treatment as prevention and pre-exposure prophylaxis. We also consider the implications of recent data from interventional and observational studies demonstrating significant reductions in the risk of HIV transmission within a serodiscordant relationship if the HIV-positive partner is taking effective ART upon PEP guidelines. Keywords: post-exposure prophylaxis, pre-exposure prophylaxis, treatment as prevention, human immunodeficiency virus

  2. Adolescent pre-exposure prophylaxis for HIV prevention: current perspectives

    Directory of Open Access Journals (Sweden)

    Machado DM

    2017-11-01

    Full Text Available Daisy Maria Machado,1 Alexandre Machado de Sant’Anna Carvalho,2 Rachel Riera3 1Disciplina de Infectologia Pediátrica, Departamento de Pediatria, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, 2Universidade Federal do Rio de Janeiro, Rio de Janeiro, 3Disciplina de Medicina Baseada em Evidências, Departamento de Medicina, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, Brazil Abstract: Adolescents are a critical population that is disproportionately impacted by the HIV epidemic. More than 2 million adolescents between the age group of 10 and 19 years are living with HIV, and millions are at risk of infection. HIV risks are considerably higher among girls, especially in high-prevalence settings such as eastern and southern Africa. In addition to girls, there are other vulnerable adolescent subgroups, such as teenagers, who use intravenous (IV drugs, gay and bisexual boys, transgender youth, male sex workers, and people who fall into more than one of these categories. Pre-exposure prophylaxis (PrEP is a new intervention for people at high risk for acquiring HIV, with an estimated HIV incidence of >3%. Recent data from trials show evidence of the efficacy of PrEP as a powerful HIV prevention tool in high-risk populations, including men who have sex with men, HIV-1-serodiscordant heterosexual couples, and IV drug users. The reported efficacy in those trials of the daily use of oral tenofovir, alone or in combination with emtricitabine, to prevent HIV infection ranged from 44% to 75% and was heavily dependent on adherence. Despite the proven efficacy of PrEP in adult trials, concerns remain about its feasibility in real-life scenarios due to stigma, cost, and limited clinician experience with PrEP delivery. Recent studies are attempting to expand the inquiry into the efficacy of such HIV prophylaxis approaches in adolescent populations, but there are still many gaps in knowledge, and no

  3. HIV-negative male couples' attitudes about pre-exposure prophylaxis (PrEP) and using PrEP with a sexual agreement.

    Science.gov (United States)

    Mitchell, Jason W; Lee, Ji-Young; Woodyatt, Cory; Bauermeister, José; Sullivan, Patrick; Stephenson, Rob

    2016-08-01

    One efficacious strategy to help prevent HIV is oral pre-exposure prophylaxis (PrEP), a daily regimen of antiretroviral treatment taken by HIV-negative individuals. Two of the recommendations of Centers for Disease Control and Prevention (CDC) guidelines for PrEP pertain to being in a relationship (i.e., male couples). Despite the recognition of how primary partners in male couples' relationships shape HIV risk and CDC's PrEP guidelines, there is a paucity of data that examine HIV-negative male couples' attitudes toward PrEP use and using PrEP with a sexual agreement. A sexual agreement is an explicit agreement made between two individuals about what sex and other related behaviors may occur within and outside of their relationship. In this qualitative study, we examine HIV-negative male couples' attitudes toward PrEP use and whether they thought PrEP could be integrated into a sexual agreement. Data for this study are drawn from couple-level interviews conducted in 2014 with 29 HIV-negative male couples who had a sexual agreement and were from Atlanta or Detroit. Both passive (e.g., flyers) and active (e.g., targeted Facebook advertisements) recruitment methods were used; the sample was stratified by agreement type. Thematic analysis was applied to identify the following themes regarding HIV-negative male couples' attitudes toward PrEP use: (1) PrEP and condom use; (2) concerns about PrEP (e.g., effectiveness, side effects, and promoting sexually risky behavior); and (3) accessibility of PrEP. Some thought PrEP could be a part of couples' agreement because it could help reduce sexual anxiety and sexual risk, and would help keep the couple safe. Others described PrEP use with an agreement as something for "others". Some were also concerned that incorporating PrEP could usurp the need for a sexual agreement in a couples' relationship. These themes highlight the need to improve informational messaging and promotion efforts about PrEP among HIV-negative male couples

  4. Reproductive decisions of couples living with HIV in Malawi: What ...

    African Journals Online (AJOL)

    policies and guidelines on HIV, AIDS and sexual and reproductive health in Malawi for ... reflect the social cultural experiences of couples living with HIV. In addition, there is ... then, treatment is available free of charge in the public hospital facilities. ... started implementing an integrated antiretroviral / PMTCT programme ...

  5. Assessment of a couples HIV counseling and testing program for pregnant women and their partners in antenatal care (ANC) in 7 provinces, Thailand.

    Science.gov (United States)

    Lolekha, Rangsima; Kullerk, Nareeluck; Wolfe, Mitchell I; Klumthanom, Kanyarat; Singhagowin, Thapanaporn; Pattanasin, Sarika; Sombat, Potjaman; Naiwatanakul, Thananda; Leartvanangkul, Chailai; Voramongkol, Nipunporn

    2014-12-24

    Couples HIV testing and counseling (CHTC) at antenatal care (ANC) settings allows pregnant women to learn the HIV status of themselves and their partners. Couples can make decisions together to prevent HIV transmission. In Thailand, men were tested at ANC settings only if their pregnant partners were HIV positive. A CHTC program based in ANC settings was developed and implemented at 16 pilot hospitals in 7 provinces during 2009-2010. Cross-sectional data were collected using standard data collection forms from all pregnant women and accompanying partners who presented at first ANC visit at 16 hospitals. CHTC data for women and partners were analyzed to determine service uptake and HIV test results among couples. In-depth interviews were conducted among hospital staff of participating hospitals during field supervision visits to assess feasibility and acceptability of CHTC services. During October 2009-April 2010, 4,524 women initiating ANC were enrolled. Of these, 2,435 (54%) women came for ANC alone; 2,089 (46%) came with partners. Among men presenting with partners, 2,003 (96%) received couples counseling. Of these, 1,723 (86%) men and all pregnant women accepted HIV testing. Among 1,723 couples testing for HIV, 1,604 (93%) returned for test results. Of these, 1,567 (98%) were concordant negative, 6 (0.4%) were concordant positive and 17 (1%) were HIV discordant (7 male+/female- and 10 male-/female+). Nine of ten (90%) executive hospital staff reported high acceptability of CHTC services. CHTC implemented in ANC settings helps identify more HIV-positive men whose partners were negative than previous practice, with high acceptability among hospital staff.

  6. Perceptions and Definitions of Power Within the Context of HIV-Negative Male Couples' Relationships.

    Science.gov (United States)

    Mitchell, Jason W; Sophus, Amber I

    2017-07-01

    Examining dynamics within relationships is critical for development of effective HIV prevention interventions for male couples. The dynamic of power has received little attention in research with male couples, though power has been reported to affect HIV risk among heterosexual couples. To help address this knowledge gap, the present cross-sectional analysis used mixed methods with dyadic data from 142 HIV-negative male couples to (1) assess partnered men's perception of who has the most power in their relationship and why, (2) examine whether partners concur about who has the most power and their reasoning for this selection, and (3) assess whether male couples' concurrence about who has the most power is associated with their engagement of condomless anal sex within and/or outside the relationship, type of relationship, and aspects of their sexual agreement. Individual- and couple-level responses about who has the most power were quantitatively assessed, whereas for why, their responses were coded qualitatively. Fifty-six percent of couples concurred about who has the most power in their relationship and of these, many said it was equal. Regarding why, themes of responses ranged from "compromise" and "shared responsibility" for those who concurred about who has the most power versus "dominant/compliant personality" and "money" among the couples who disagreed about who has the most power in their relationship. Concordance about who has the most power was only associated with condomless anal sex within the relationship. Further research is warranted to examine how power may affect other dynamics of male couples' relationships and risk-related behaviors.

  7. Gender inequality and the risk of HIV among married couples in North India

    OpenAIRE

    Bloom, Shelah S.; Agrawal, Alpna; Singh, Kaushalendra K.; Suchindran, Chirayath M.

    2014-01-01

    This study investigated the distribution and determinants of HIV risks among married couples in North India. Gender inequality emerged as a potential driver of HIV risks in this region. Data collection took place in 2003 in a probability survey of 3,385 couples living in India’s most populous state – Uttar Pradesh – and Uttaranchal. Couples’ analyses utilizing generalized estimating equations showed that compared with husbands, wives were less knowledgeable about HIV (OR=0.31, 95% CI= 0.27–0....

  8. Unintended pregnancy among HIV positive couples receiving integrated HIV counseling, testing, and family planning services in Zambia.

    Science.gov (United States)

    Wall, Kristin M; Haddad, Lisa; Vwalika, Bellington; Htee Khu, Naw; Brill, Ilene; Kilembe, William; Stephenson, Rob; Chomba, Elwyn; Vwalika, Cheswa; Tichacek, Amanda; Allen, Susan

    2013-01-01

    We describe rates of unintended pregnancy among HIV positive couples in Lusaka, Zambia. We also identify factors associated with unintended pregnancy among oral contraceptive pill (OCP) using couples in this cohort. Data were analyzed from couples randomized in a factorial design to two family planning intervention videos. Rates of unintended pregnancy were stratified by contraceptive method used at time of pregnancy. Predictors of time to unintended pregnancy among OCP users were determined via multivariate Cox modeling. The highest rates of unintended pregnancy were observed among couples requesting condoms only (26.4/100CY) or OCPs (20.7/100CY); these rates were not significantly different. OCP users accounted for 37% of the couple-years (CY) observed and 87% of unintended pregnancies. Rates of unintended pregnancy for injectable (0.7/100CY) and intrauterine device (1.6/100CY) users were significantly lower relative to condom only users. No pregnancies occurred among contraceptive implant users or after tubal ligation. Factors associated (psex without a condom. Long-acting reversible contraceptive methods were effective in the context of integrated couples HIV prevention and contraceptive services. Injectable methods were also effective in this context. Given the high user failure rate of OCPs, family planning efforts should promote longer-acting methods among OCP users wishing to avoid pregnancy. Where other methods are not available or acceptable, OCP adherence counseling is needed, especially among younger and new OCP users. ClinicalTrials.gov NCT00067522.

  9. Short-term mobility and the risk of HIV infection among married couples in the fishing communities along Lake Victoria, Kenya.

    Directory of Open Access Journals (Sweden)

    Zachary A Kwena

    Full Text Available Mobility has long been associated with high HIV prevalence. We sought to assess sex differences in the relationship between mobility and risk for HIV infection among married couples in the fishing communities.We conducted 1090 gender-matched interviews and rapid HIV testing with 545 couples proportionally representing all the different sizes of the fish-landing beaches in Kisumu County. We contacted a random sample of fishermen as our index participants and asked them to enroll in the study together with their spouses. The consenting couples were separated into different private rooms for concurrent interviews and thereafter reunited for couple rapid HIV counselling and testing. In addition to socio-economic and behavioural data, we collected information on overnight travels and divided couples in 4 groups as follows both partners not mobile, both partners mobile, only woman mobile, and only man mobile. Other than descriptive statistics, we used X(2 and U tests to compare groups of variables and multivariate logistic regression to measure association between mobility and HIV infection.We found significant differences in the number of trips women travelled in the preceding month (mean 4.6, SD 7.1 compared to men (mean 3.3, SD 4.9; p<0.01 and when the women did travel, they were more likely to spend more days away from home than their male partners (mean 5.2 [SD 7.2] versus 3.4 SD 5.6; p = 0.01. With an HIV prevalence of 22.7% in women compared to 20.9% among men, mobile women who had non-mobile spouses had 2.1 times the likelihood of HIV infection compared to individuals in couples where both partners were non-mobile.The mobility of fishermen's spouses is associated with HIV infection that is not evident among fishermen themselves. Therefore, interventions in this community could be a combination of sex-specific programming that targets women and combined programming for couples.

  10. East African Medical Journal - Vol 85, No 7 (2008)

    African Journals Online (AJOL)

    Stakeholders perception of HIV sero-discordant couples in western Kenya · EMAIL FREE FULL TEXT EMAIL FREE FULL TEXT · DOWNLOAD FULL TEXT DOWNLOAD FULL TEXT. E Were, K Wools-Kaloustian, J Baliddawa, PO Ayuo, J Sidle, K Fife, 326-333. http://dx.doi.org/10.4314/eamj.v85i7.9650 ...

  11. Qualitative analysis of an educational intervention with HIV-discordant heterosexual Latino couples.

    Science.gov (United States)

    Pérez-Jiménez, David; Orengo-Aguayo, Rosaura E

    2011-12-01

    This qualitative analysis elucidates the potential elements of the intervention that may be effective in terms of a) increasing knowledge about HIV/ AIDS in the members of this population; b) increasing the use of male condoms and the practice of mutual masturbation; and c) changing opinions toward male condom use and mutual masturbation. Five heterosexual HIV-discordant couples participated in the adapted intervention, which consisted of four three-hour-long sessions. One month after the intervention, we conducted a qualitative semi-structured interview with every participant to evaluate issues related to the process and content of the activities comprising the intervention, the impact of the intervention, logistics, and recruitment and retention as well as to make a more general evaluation. The information was submitted to qualitative content analysis. After the intervention, participants reported having better attitudes regarding safer sex, particularly in terms of condom use. A reason given by the participants to feel more positive toward condom use and mutual masturbation was that these practices could prevent the infection of the HIV-negative partner. This study provides important evidence of an intervention that promises to be efficacious in preventing some high-risk sexual behaviors among Latino HIV-discordant heterosexual couples. The evidence presented seems to suggest that an intervention that includes basic relevant information about HIV/AIDS, that explains the benefits of condom use and other safer sex options, and that provides effective negotiation and communication strategies could significantly reduce HIV transmission among these couples.

  12. How reliable are self-reports of HIV status disclosure? Evidence from couples in Malawi.

    Science.gov (United States)

    Conroy, Amy A; Wong, Lauren H

    2015-11-01

    The majority of research on human immunodeficiency virus (HIV) disclosure utilizes the perspective from a single individual, which cannot be substantiated in the absence of supporting data such as from a primary partner. The objectives of this study were to evaluate: (1) the extent to which self-reported HIV disclosure was confirmed by a primary partner; (2) individual and relationship-level predictors of self-reported versus confirmed disclosure; and (3) whether confirmed disclosure was a stronger predictor of correctly assessing a partner's HIV status compared to self-reported disclosure. As part of an 8-wave longitudinal study from 2009 to 2011 in southern Malawi, 366 individuals (183 couples) were interviewed about their primary relationship (wave 3), individually tested for HIV (wave 4), and then asked whether they disclosed to their primary partner (wave 5). While 93% of respondents reported that they disclosed, only 64% of respondents had confirmed reports from their partner. Having communicated with partner about HIV was positively associated with self-reported disclosure; this association remained significant but became more precise in the models for confirmed disclosure. Confirmed disclosure, but not self-report, was a significant predictor of correctly assessing a partner's HIV status. Being male, having lower perceived partner infidelity, having higher relationship unity, and testing HIV-negative were positively and significantly associated with correct assessment. Dyadic data from two partners provide an improved measure of disclosure as compared to a single individual's self-report and could be used to identify behavioral and biomedical opportunities to prevent HIV transmission within couples. Copyright © 2015 Elsevier Ltd. All rights reserved.

  13. A European multicientre study on the comparison of HIV-1 viral loads between VERIS HIV-1 Assay and Roche COBAS® TAQMAN® HIV-1 test, Abbott RealTime HIV-1 Assay, and Siemens VERSANT HIV-1 Assay.

    Science.gov (United States)

    Braun, Patrick; Delgado, Rafael; Drago, Monica; Fanti, Diana; Fleury, Hervé; Hofmann, Jörg; Izopet, Jacques; Kühn, Sebastian; Lombardi, Alessandra; Mancon, Alessandro; Marcos, Mª Angeles; Mileto, Davide; Sauné, Karine; O'Shea, Siobhan; Pérez-Rivilla, Alfredo; Ramble, John; Trimoulet, Pascale; Vila, Jordi; Whittaker, Duncan; Artus, Alain; Rhodes, Daniel

    2017-07-01

    Viral load monitoring is essential for patients under treatment for HIV. Beckman Coulter has developed the VERIS HIV-1 Assay for use on the novel, automated DxN VERIS Molecular Diagnostics System. ¥ OBJECTIVES: Evaluation of the clinical performance of the new quantitative VERIS HIV-1 Assay at multiple EU laboratories. Method comparison with the VERIS HIV-1 Assay was performed with 415 specimens at 5 sites tested with COBAS ® AmpliPrep/COBAS ® TaqMan ® HIV-1 Test, v2.0, 169 specimens at 3 sites tested with RealTime HIV-1 Assay, and 202 specimens from 2 sites tested with VERSANT HIV-1 Assay. Patient monitoring sample results from 4 sites were also compared. Bland-Altman analysis showed the average bias between VERIS HIV-1 Assay and COBAS HIV-1 Test, RealTime HIV-1 Assay, and VERSANT HIV-1 Assay to be 0.28, 0.39, and 0.61 log 10 cp/mL, respectively. Bias at low end levels below 1000cp/mL showed predicted bias to be <0.3 log 10 cp/mL for VERIS HIV-1 Assay versus COBAS HIV-1 Test and RealTime HIV-1 Assay, and <0.5 log 10 cp/mL versus VERSANT HIV-1 Assay. Analysis on 174 specimens tested with the 0.175mL volume VERIS HIV-1 Assay and COBAS HIV-1 Test showed average bias of 0.39 log 10 cp/mL. Patient monitoring results using VERIS HIV-1 Assay demonstrated similar viral load trends over time to all comparators. The VERIS HIV-1 Assay for use on the DxN VERIS System demonstrated comparable clinical performance to COBAS ® HIV-1 Test, RealTime HIV-1 Assay, and VERSANT HIV-1 Assay. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. Acceptability of HIV/AIDS testing among pre-marital couples in Iran (2012).

    Science.gov (United States)

    Ayatollahi, Jamshid; Nasab Sarab, Mohammad Ali Bagheri; Sharifi, Mohammad Reza; Shahcheraghi, Seyed Hossein

    2014-07-01

    Human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS) is a lifestyle-related disease. This disease is transmitted through unprotected sex, contaminated needles, infected blood transfusion and from mother to child during pregnancy and delivery. Prevention of infection with HIV, mainly through safe sex and needle exchange programmes is a solution to prevent the spread of the disease. Knowledge about HIV state helps to prevent and subsequently reduce the harm to the later generation. The purpose of this study was to assess the willingness rate of couples referred to the family regulation pre-marital counselling centre for performing HIV test before marriage in Yazd. In this descriptive study, a simple random sampling was done among people referred to Akbari clinic. The couples were 1000 men and 1000 women referred to the premarital counselling centre for pre-marital HIV testing in Yazd in the year 2012. They were in situations of pregnancy, delivery or nursing and milking. The data were analyzed using Statistical Package for the Social Sciences (SPSS) software and chi-square statistical test. There was a significant statistical difference between the age groups about willingness for HIV testing before marriage (P marriage was significant. Therefore, HIV testing before marriage as a routine test was suggested.

  15. Insights in Public Health: In What Ways are Hawaii's HIV Prevention Services Engaging Gay Male Couples and Using Technology?

    Science.gov (United States)

    Sophus, Amber I; Fujitani, Loren; Vallabhbhai, Samantha; Antonio, Jo Anna; Yang, Pua Lani; Elliott, Elyssa; Mitchell, Jason W

    2018-02-01

    Partner-oriented services and Health Information and Communication technology (HICT) in the forms of mHealth (eg, smartphone applications), eHealth (eg, interactive websites), telemedicine, and social media play an important and growing role in HIV prevention. Accordingly, the present study sought to describe: (1) the primary and secondary HIV prevention services available in Hawai'i, (2) the prevention services that are available for gay male couples and partners, and (3) the prevention services that use HICT. Information about prevention services and use of HICT were obtained from websites and phone calls made to 19 organizations in the state, including the Hawai'i Department of Health. Overall, partner-oriented services were limited and only 1 couples-based service was currently being offered. Technology, namely social media, was used by 14 organizations, primarily to increase HIV awareness and advertise events. These findings may inform how best to adapt and better leverage the use of innovative technological tools to help expand access to HIV testing and counseling, sexual health education, and case management services for gay male couples and other MSM populations in the state.

  16. Qualitative Analysis of an Educational Intervention with HIV-Discordant Heterosexual Latino Couples

    Science.gov (United States)

    Pérez-Jiménez, David; Orengo-Aguayo, Rosaura E.

    2012-01-01

    Objective This qualitative analysis elucidates the potential elements of the intervention that may be effective in terms of a) increasing knowledge about HIV/AIDS in the members of this population; b) increasing the use of male condoms and the practice of mutual masturbation; and c) changing opinions toward male condom use and mutual masturbation. Methods Five heterosexual HIV-discordant couples participated in the adapted intervention, which consisted of four three-hour-long sessions. One month after the intervention, we conducted a qualitative semi-structured interview with every participant to evaluate issues related to the process and content of the activities comprising the intervention, the impact of the intervention, logistics, and recruitment and retention as well as to make a more general evaluation. The information was submitted to qualitative content analysis. Results After the intervention, participants reported having better attitudes regarding safer sex, particularly in terms of condom use. A reason given by the participants to feel more positive toward condom use and mutual masturbation was that these practices could prevent the infection of the HIV-negative partner. Conclusion This study provides important evidence of an intervention that promises to be efficacious in preventing some high-risk sexual behaviors among Latino HIV-discordant heterosexual couples. The evidence presented seems to suggest that an intervention that includes basic relevant information about HIV/AIDS, that explains the benefits of condom use and other safer sex options, and that provides effective negotiation and communication strategies could significantly reduce HIV transmission among these couples. PMID:22263299

  17. Extending the Minority Stress Model to Incorporate HIV-Positive Gay and Bisexual Men's Experiences: a Longitudinal Examination of Mental Health and Sexual Risk Behavior.

    Science.gov (United States)

    Rendina, H Jonathon; Gamarel, Kristi E; Pachankis, John E; Ventuneac, Ana; Grov, Christian; Parsons, Jeffrey T

    2017-04-01

    Minority stress theory represents the most plausible conceptual framework for explaining health disparities for gay and bisexual men (GBM). However, little focus has been given to including the unique stressors experienced by HIV-positive GBM. We explored the role of HIV-related stress within a minority stress model of mental health and condomless anal sex. Longitudinal data were collected on a diverse convenience sample of 138 highly sexually active, HIV-positive GBM in NYC regarding sexual minority (internalized homonegativity and gay-related rejection sensitivity) and HIV-related stressors (internalized HIV stigma and HIV-related rejection sensitivity), emotion dysregulation, mental health (symptoms of depression, anxiety, sexual compulsivity, and hypersexuality), and sexual behavior (condomless anal sex with all male partners and with serodiscordant male partners). Across both sexual minority and HIV-related stressors, internalized stigma was significantly associated with mental health and sexual behavior outcomes while rejection sensitivity was not. Moreover, path analyses revealed that emotion dysregulation mediated the influence of both forms of internalized stigma on symptoms of depression/anxiety and sexual compulsivity/hypersexuality as well as serodiscordant condomless anal sex. We identified two targets of behavioral interventions that may lead to improvements in mental health and reductions in sexual transmission risk behaviors-maladaptive cognitions underlying negative self-schemas and difficulties with emotion regulation. Techniques for cognitive restructuring and emotion regulation may be particularly useful in the development of interventions that are sensitive to the needs of this population while also highlighting the important role that structural interventions can have in preventing these disparities for future generations.

  18. Maternal Tenofovir Disoproxil Fumarate Use During Pregnancy Is Not Associated With Adverse Perinatal Outcomes Among HIV-infected East African Women: A Prospective Study.

    Science.gov (United States)

    Pintye, Jillian; Baeten, Jared M; Celum, Connie; Mugo, Nelly; Ngure, Kenneth; Were, Edwin; Bukusi, Elizabeth A; John-Stewart, Grace; Heffron, Renee A

    2017-12-19

    Tenofovir disoproxil fumarate (TDF) is commonly used in antiretroviral treatment (ART) and pre-exposure prophylaxis regimens. We evaluated the relationship between adverse perinatal outcomes and prenatal TDF use. Longitudinal data were analyzed from human immunodeficiency virus (HIV)-infected women who became pregnant during 2 HIV prevention studies conducted among HIV-serodiscordant couples in Kenya and Uganda. Pregnancies included were singleton, not terminated by an induced abortion, and had documented 3-drug ART use. Multivariate generalized estimating equation models were used to determine the association of prenatal TDF and perinatal outcomes. The most frequent ART regimens were TDF/3TC/EFV (39%) and AZT/3TC/NVP (34%); 49% of pregnancies had prenatal TDF exposure and 6% used a protease inhibitor. Neonatal death, preterm birth, and pregnancy loss occurred in 2%, 8%, and 12% of pregnancies, respectively. No differences were observed between pregnancies with and without exposure to TDF in the frequency of pregnancy loss (adjusted prevalence rate ratio [aPRR] 1.19, P = .8) or neonatal death (aPRR 0.68, P = .6). Preterm birth occurred less frequently among pregnancies exposed to TDF (aPRR, 0.34, P = .02). Maternal TDF use did not adversely affect perinatal outcomes. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

  19. The Study of HIV and Antenatal Care Integration in Pregnancy in Kenya: Design, Methods, and Baseline Results of a Cluster-Randomized Controlled Trial

    Science.gov (United States)

    Turan, Janet M.; Steinfeld, Rachel L.; Onono, Maricianah; Bukusi, Elizabeth A.; Woods, Meghan; Shade, Starley B.; Washington, Sierra; Marima, Reson; Penner, Jeremy; Ackers, Marta L.; Mbori-Ngacha, Dorothy; Cohen, Craig R.

    2012-01-01

    Background Despite strong evidence for the effectiveness of anti-retroviral therapy for improving the health of women living with HIV and for the prevention of mother-to-child transmission (PMTCT), HIV persists as a major maternal and child health problem in sub-Saharan Africa. In most settings antenatal care (ANC) services and HIV treatment services are offered in separate clinics. Integrating these services may result in better uptake of services, reduction of the time to treatment initiation, better adherence, and reduction of stigma. Methodology/Principal Findings A prospective cluster randomized controlled trial design was used to evaluate the effects of integrating HIV treatment into ANC clinics at government health facilities in rural Kenya. Twelve facilities were randomized to provide either fully integrated services (ANC, PMTCT, and HIV treatment services all delivered in the ANC clinic) or non-integrated services (ANC clinics provided ANC and basic PMTCT services and referred clients to a separate HIV clinic for HIV treatment). During June 2009– March 2011, 1,172 HIV-positive pregnant women were enrolled in the study. The main study outcomes are rates of maternal enrollment in HIV care and treatment, infant HIV testing uptake, and HIV-free infant survival. Baseline results revealed that the intervention and control cohorts were similar with respect to socio-demographics, male partner HIV testing, sero-discordance of the couple, obstetric history, baseline CD4 count, and WHO Stage. Challenges faced while conducting this trial at low-resource rural health facilities included frequent staff turnover, stock-outs of essential supplies, transportation challenges, and changes in national guidelines. Conclusions/Significance This is the first randomized trial of ANC and HIV service integration to be conducted in rural Africa. It is expected that the study will provide critical evidence regarding the implementation and effectiveness of this service delivery

  20. The study of HIV and antenatal care integration in pregnancy in Kenya: design, methods, and baseline results of a cluster-randomized controlled trial.

    Directory of Open Access Journals (Sweden)

    Janet M Turan

    Full Text Available Despite strong evidence for the effectiveness of anti-retroviral therapy for improving the health of women living with HIV and for the prevention of mother-to-child transmission (PMTCT, HIV persists as a major maternal and child health problem in sub-Saharan Africa. In most settings antenatal care (ANC services and HIV treatment services are offered in separate clinics. Integrating these services may result in better uptake of services, reduction of the time to treatment initiation, better adherence, and reduction of stigma.A prospective cluster randomized controlled trial design was used to evaluate the effects of integrating HIV treatment into ANC clinics at government health facilities in rural Kenya. Twelve facilities were randomized to provide either fully integrated services (ANC, PMTCT, and HIV treatment services all delivered in the ANC clinic or non-integrated services (ANC clinics provided ANC and basic PMTCT services and referred clients to a separate HIV clinic for HIV treatment. During June 2009- March 2011, 1,172 HIV-positive pregnant women were enrolled in the study. The main study outcomes are rates of maternal enrollment in HIV care and treatment, infant HIV testing uptake, and HIV-free infant survival. Baseline results revealed that the intervention and control cohorts were similar with respect to socio-demographics, male partner HIV testing, sero-discordance of the couple, obstetric history, baseline CD4 count, and WHO Stage. Challenges faced while conducting this trial at low-resource rural health facilities included frequent staff turnover, stock-outs of essential supplies, transportation challenges, and changes in national guidelines.This is the first randomized trial of ANC and HIV service integration to be conducted in rural Africa. It is expected that the study will provide critical evidence regarding the implementation and effectiveness of this service delivery strategy, with important implications for programs striving

  1. What Primary Care Providers Need to Know about Pre-Exposure Prophylaxis (PrEP) for HIV Prevention: Narrative Review

    Science.gov (United States)

    Krakower, Douglas; Mayer, Kenneth H.

    2013-01-01

    As HIV prevalence climbs globally, including more than 50,000 new infections per year in the United States, we need effective HIV prevention strategies. The use of antiretrovirals for pre-exposure prophylaxis (known as “PrEP”) among high-risk HIV-uninfected persons is emerging as one such strategy. Randomized controlled trials have demonstrated that once daily oral PrEP decreased HIV incidence among at-risk MSM and African heterosexuals, including HIV serodiscordant couples. An additional randomized control trial of a pericoital topical application of antiretroviral microbicide gel reduced HIV incidence among at-risk heterosexual South African women. Two other studies in African women did not demonstrate the efficacy of oral or topical PrEP, raising concerns about adherence patterns and efficacy in this population. The FDA Antiretroviral Advisory Panel reviewed these studies and additional data in May 2012 and recommended the approval of oral tenofovir-emtricitabine for PrEP in high-risk populations. Patients may seek PrEP from their primary care providers and those on PrEP require monitoring. Thus, primary care providers should become familiar with PrEP. This review outlines the current state of knowledge about PrEP as it pertains to primary care including identification of individuals likely to benefit from PrEP, counseling to maximize adherence and minimize potential increases in risky behavior, and monitoring for potential drug toxicities, HIV acquisition, and antiretroviral drug resistance. Issues related to cost and insurance coverage are also discussed. Recent data suggest that PrEP, in conjunction with other prevention strategies, holds promise in helping to curtail the HIV epidemic. PMID:22821365

  2. Promotion of couples' voluntary counselling and testing for HIV through influential networks in two African capital cities.

    Science.gov (United States)

    Allen, Susan; Karita, Etienne; Chomba, Elwyn; Roth, David L; Telfair, Joseph; Zulu, Isaac; Clark, Leslie; Kancheya, Nzali; Conkling, Martha; Stephenson, Rob; Bekan, Brigitte; Kimbrell, Katherine; Dunham, Steven; Henderson, Faith; Sinkala, Moses; Carael, Michel; Haworth, Alan

    2007-12-11

    Most new HIV infections in Africa are acquired from cohabiting heterosexual partners. Couples' Voluntary Counselling and Testing (CVCT) is an effective prevention strategy for this group. We present our experience with a community-based program for the promotion of CVCT in Kigali, Rwanda and Lusaka, Zambia. Influence Network Agents (INAs) from the health, religious, non-governmental, and private sectors were trained to invite couples for CVCT. Predictors of successful promotion were identified using a multi-level hierarchical analysis. In 4 months, 9,900 invitations were distributed by 61 INAs, with 1,411 (14.3%) couples requesting CVCT. INAs in Rwanda distributed fewer invitations (2,680 vs. 7,220) and had higher response rates (26.9% vs. 9.6%), than INAs in Zambia. Context of the invitation event, including a discreet location such as the INA's home (OR 3.3-3.4), delivery of the invitation to both partners in the couple (OR 1.6-1.7) or to someone known to the INA (OR 1.7-1.8), and use of public endorsement (OR 1.7-1.8) were stronger predictors of success than INA or couple-level characteristics. Predictors of successful CVCT promotion included strategies that can be easily implemented in Africa. As new resources become available for Africans with HIV, CVCT should be broadly implemented as a point of entry for prevention, care and support.

  3. Impact of marriage on HIV/AIDS risk behaviors among impoverished, at-risk couples: a multilevel latent variable approach.

    Science.gov (United States)

    Stein, Judith A; Nyamathi, Adeline; Ullman, Jodie B; Bentler, Peter M

    2007-01-01

    Studies among normative samples generally demonstrate a positive impact of marriage on health behaviors and other related attitudes. In this study, we examine the impact of marriage on HIV/AIDS risk behaviors and attitudes among impoverished, highly stressed, homeless couples, many with severe substance abuse problems. A multilevel analysis of 368 high-risk sexually intimate married and unmarried heterosexual couples assessed individual and couple-level effects on social support, substance use problems, HIV/AIDS knowledge, perceived HIV/AIDS risk, needle-sharing, condom use, multiple sex partners, and HIV/AIDS testing. More variance was explained in the protective and risk variables by couple-level latent variable predictors than by individual latent variable predictors, although some gender effects were found (e.g., more alcohol problems among men). The couple-level variable of marriage predicted lower perceived risk, less deviant social support, and fewer sex partners but predicted more needle-sharing.

  4. Safer Conception for Couples Affected by HIV: Structural and Cultural Considerations in the Delivery of Safer Conception Care in Uganda.

    Science.gov (United States)

    Mindry, Deborah; Wanyenze, Rhoda K; Beyeza-Kashesya, Jolly; Woldetsadik, Mahlet A; Finocchario-Kessler, Sarah; Goggin, Kathy; Wagner, Glenn

    2017-08-01

    In countries with high HIV prevalence and high fertility desires, the rights of HIV-affected couples to have children are a pressing issue. Conception among people living with HIV carries risks for both horizontal and vertical HIV transmission. In Uganda ~100,000 HIV-infected women become pregnant annually. Providers face a number of challenges to preventing HIV transmission, reducing unplanned pregnancies, and ensuring safer conception. We report findings from interviews with 27 HIV-affected couples (54 individuals) in Uganda. We explored key cultural and structural factors shaping couples' childbearing decisions. Our data reveal a complex intersection of gender norms, familial expectations, relationship dynamics, and HIV stigma influencing their decisions. Participants provided insights regarding provider bias, stigma, and the gendering of reproductive healthcare. To reduce horizontal transmission HIV and family planning clinics must address men's and women's concerns regarding childbearing with specific attention to cultural and structural challenges.

  5. Motivators of couple HIV counseling and testing (CHCT uptake in a rural setting in Uganda

    Directory of Open Access Journals (Sweden)

    Victoria Nannozi

    2017-01-01

    Full Text Available Abstract Background Couple HIV Counseling and Testing (CHCT is one of the key preventive strategies used to reduce the spread of HIV. In Uganda, HIV prevalence among married/living together is 7.2% among women and 7.6% among men. CHCT can help ease disclosure of HIV-positive status, which in turn may help increase opportunities to get social support and reduce new infections. The uptake of CHCT among attendees of health facilities in rural Uganda is as high as 34%. The purpose of this study was to explore the motivators of CHCT uptake in Mukono district, a rural setting in Uganda. Methods The study was conducted in two sub-counties in a rural district (Mukono district about 28 km east of the capital Kampala, using a descriptive and explorative qualitative research design. Specifically, we conducted focus group discussions and key informant interviews with HIV focal persons, village health team (VHT members, religious leaders and political leaders. We also interviewed persons in couple relationships. Data was analysed using NVivo 8 software. Ethical clearance was received from the Mengo Hospital Research Review Board and from the Uganda National Council of Science and Technology. Results The study was conducted from June 2013 to July 2013 We conducted 4 focus group discussions, 10 key informant interviews and interviewed 53 persons in couple relationships. None of the participants were a couple. The women were 68% (36/53 and 49% (26/53 of them were above 29 years old. The motivators of CHCT uptake were; perceived benefit of HIV testing, sickness of a partner or child in the family and suspicion of infidelity. Other important motivators were men involvement in antenatal care (ANC attendance and preparation for marriage. Conclusion The motivators for CHCT uptake included the perceived benefit of HIV testing, sickness of a partner or child, preparation for marriage, lack of trust among couples and men involvement in antenatal care. Greater

  6. Motivators of couple HIV counseling and testing (CHCT) uptake in a rural setting in Uganda.

    Science.gov (United States)

    Nannozi, Victoria; Wobudeya, Eric; Matsiko, Nicholas; Gahagan, Jacqueline

    2017-01-23

    Couple HIV Counseling and Testing (CHCT) is one of the key preventive strategies used to reduce the spread of HIV. In Uganda, HIV prevalence among married/living together is 7.2% among women and 7.6% among men. CHCT can help ease disclosure of HIV-positive status, which in turn may help increase opportunities to get social support and reduce new infections. The uptake of CHCT among attendees of health facilities in rural Uganda is as high as 34%. The purpose of this study was to explore the motivators of CHCT uptake in Mukono district, a rural setting in Uganda. The study was conducted in two sub-counties in a rural district (Mukono district) about 28 km east of the capital Kampala, using a descriptive and explorative qualitative research design. Specifically, we conducted focus group discussions and key informant interviews with HIV focal persons, village health team (VHT) members, religious leaders and political leaders. We also interviewed persons in couple relationships. Data was analysed using NVivo 8 software. Ethical clearance was received from the Mengo Hospital Research Review Board and from the Uganda National Council of Science and Technology. The study was conducted from June 2013 to July 2013 We conducted 4 focus group discussions, 10 key informant interviews and interviewed 53 persons in couple relationships. None of the participants were a couple. The women were 68% (36/53) and 49% (26/53) of them were above 29 years old. The motivators of CHCT uptake were; perceived benefit of HIV testing, sickness of a partner or child in the family and suspicion of infidelity. Other important motivators were men involvement in antenatal care (ANC) attendance and preparation for marriage. The motivators for CHCT uptake included the perceived benefit of HIV testing, sickness of a partner or child, preparation for marriage, lack of trust among couples and men involvement in antenatal care. Greater attention to enhancers of CHCT programming is needed in trying to

  7. The impact of parenting on gay male couples' relationships, sexuality, and HIV risk

    Science.gov (United States)

    Huebner, David M.; Mandic, Carmen Gómez; Mackaronis, Julia E.; Beougher, Sean C.; Hoff, Colleen C.

    2014-01-01

    Parenthood changes couples' relationships across multiple domains, generally decreasing relationship quality, sexual satisfaction, and sexual frequency. Emerging research suggests that gay couples who are parenting might experience similar challenges. However, such changes might have even more profound implications for gay couples' health, and in particular their HIV risk, given the somewhat different ways in which they negotiate and tolerate sexual behaviors with outside partners. We aimed to examine these issues in a qualitative analysis of interviews from 48 gay male couples who were actively parenting children. Findings suggest that parenthood increases men's commitment to their primary relationship while simultaneously decreasing time and energy for relationship maintenance, and generally decreasing sexual satisfaction. These challenges alone did not generally result in greater infidelity or HIV risk, as most men reported successfully coping with such changes through a combination of acceptance and revaluing what is important in their relationships. Additionally, couples reported negotiating agreements regarding sex with outside partners that closely resemble those documented in studies of gay couples who are not parents. Men reported that parenthood typically decreased their opportunities to engage in sex with outside partners, but also posed barriers to talking about these behaviors with their partners and healthcare providers. HIV-related sexual risk behavior was relatively rare, but nevertheless present in some men. Providers should assess sexual function as a regular part of their work with gay couples who parent, and facilitate opportunities for men to discuss their sexual agreements both with their primary partners and with relevant healthcare providers. PMID:25674355

  8. Breaking Binaries? Biomedicine and Serostatus Borderlands among Couples with Mixed HIV Status.

    Science.gov (United States)

    Persson, Asha; Newman, Christy E; Ellard, Jeanne

    2017-01-01

    With recent breakthroughs in HIV treatment and prevention, the meanings of HIV-positivity and HIV-negativity are changing at biomedical and community levels. We explore how binary constructions of HIV serostatus identities are giving way to something more complex that brings both welcome possibilities and potential concerns. We draw on research with couples with mixed HIV status to argue that, in the context of lived experiences, serostatus identities have always been more ambiguous than allowed for in HIV discourse. However, their supposed dichotomous quality seems even more dubious now in view of contemporary biomedical technologies. Invoking the anthropological concept of "borderlands," we consider how biomedicine is generating more diverse serostatus identities, widening the options for how to live with HIV, and eroding the stigmatizing serostatus binary that has haunted the epidemic. But we also ask whether this emerging borderland, and its "normalizing" tendencies, is concomitantly giving rise to new and troubling binaries.

  9. Hypersexual, Sexually Compulsive, or Just Highly Sexually Active? Investigating Three Distinct Groups of Gay and Bisexual Men and Their Profiles of HIV-Related Sexual Risk

    Science.gov (United States)

    Rendina, H. Jonathon; Ventuneac, Ana; Moody, Raymond L.; Grov, Christian

    2015-01-01

    Emerging research supports the notion that sexual compulsivity (SC) and hypersexual disorder (HD) among gay and bisexual men (GBM) might be conceptualized as comprising three groups—Neither SC nor HD; SC only, and Both SC and HD—that capture distinct levels of severity across the SC/HD continuum. We examined data from 370 highly sexually active GBM to assess how the three groups compare across a range of risk factors for HIV infection. Comparisons focused on psychosexual measures—temptation for condomless anal sex (CAS), self-efficacy for avoiding CAS, sexual excitation and inhibition—as well as reports of actual sexual behavior. Nearly half (48.9 %) of this highly sexually active sample was classified as Neither SC nor HD, 30 % as SC Only, and 21.1 % as Both SC and HD. While we found no significant differences between the three groups on reported number of male partners, anal sex acts, or anal sex acts with serodiscordant partners, the Both SC and HD group reported higher numbers of CAS acts and CAS acts with serodiscordant partners and also had a higher proportion of their anal sex acts without condoms compared to the SC Only group. Our findings support the validity of a three-group classification system of SC/HD severity in differentiating psychosexual and HIV-related sexual risk behavior outcomes in a sample of GBM who report similarly high levels of sexual activity. Notwithstanding the need for sex positive HIV prevention programs, interventions that attempt to help Both SC and HD men deal with distress and address their psychosexual needs specifically may derive HIV prevention benefits. PMID:25750052

  10. Clinical presentation and opportunistic infections in HIV-1, HIV-2 and HIV-1/2 dual seropositive patients in Guinea-Bissau

    DEFF Research Database (Denmark)

    Sørensen, Allan; Jespersen, Sanne; Katzenstein, Terese L

    2016-01-01

    HIV-2 is prevalent. In this study, we aimed to characterize the clinical presentations among HIV-1, HIV-2 and HIV-1/2 dual seropositive patients. Methods: In a cross-sectional study, newly diagnosed HIV patients attending the HIV outpatient clinic at Hospital Nacional Sim~ao Mendes in Guinea......-Bissau were enrolled. Demographical and clinical data were collected and compared between HIV-1, HIV-2 and HIV-1/2 dual seropositive patients. Results: A total of 169 patients (76% HIV-1, 17% HIV-2 and 6% HIV 1/2) were included in the study between 21 March 2012 and 14 December 2012. HIV-1 seropositive...... antigen. Conclusion: HIV-1 and HIV-1/2 seropositive patients have lower CD4 cell counts than HIV-2 seropositive patients when diagnosed with HIV with only minor clinical and demographic differences among groups. Few patients were diagnosed with TB and cryptococcal disease was not found to be a major...

  11. Evolving treatment implementation among HIV-infected pregnant women and their partners: results from a national surveillance study in Italy, 2001-2015.

    Science.gov (United States)

    Floridia, Marco; Frisina, Valentina; Ravizza, Marina; Marconi, Anna Maria; Pinnetti, Carmela; Cetin, Irene; Sansone, Matilde; Molinari, Atim; Cervi, Francesca; Meloni, Alessandra; Luzi, Kety; Masuelli, Giulia; Tamburrini, Enrica

    2017-06-01

    The current global and national indications for antiretroviral treatment (ART, usually triple combination therapy) in adolescent and adults, including pregnant women, recommend early ART before immunologic decline, pre-exposure chemoprophylaxis (PrEP), and treatment of HIV-negative partners in serodiscordant couples. There is limited information on the implementation of these recommendations among pregnant women with HIV and their partners. The present analysis was performed in 2016, using data from clinical records of pregnant women with HIV, followed between 2001 and 2015 at hospital or university clinics within a large, nationally representative Italian cohort study. The study period was divided in three intervals of five years each (2001-2005, 2006-2010, 2011-2015), and the analysis evaluated temporal trends in rates of HIV diagnosis in pregnancy, maternal antiretroviral treatment at conception, prevalence of HIV infection among partners of pregnant women with HIV, and proportion of seronegative and seropositive male partners receiving antiretroviral treatment. The analysis included 2755 pregnancies in women with HIV. During the three time intervals considered the rate of HIV diagnosis in pregnancy (overall 23.3%), and the distribution of HIV status among male partners (overall 48.7% HIV-negative, 28.6% HIV-positive and 22.8% unknown) remained substantially unchanged. Significant increases were observed in the proportion of women with HIV diagnosed before pregnancy who were on antiretroviral treatment at conception (from 62.0% in 2001-2005 to 81.3% in 2011-2015, P  HIV-positive partners on antiretroviral treatment (from 73.3% in 2001-2005 to 95.8% in 2011-2015, P  = 0.002). Antiretroviral treatment was administered in 99.1% of the pregnancies that did not end early because of miscarriage, termination, or intrauterine death, and in 75.3% of those not ending in a live birth. No implementation of antiretroviral treatment was introduced among male HIV

  12. Integrating HIV Prevention and Relationship Education for Young Same-Sex Male Couples: A Pilot Trial of the 2GETHER Intervention.

    Science.gov (United States)

    Newcomb, Michael E; Macapagal, Kathryn R; Feinstein, Brian A; Bettin, Emily; Swann, Gregory; Whitton, Sarah W

    2017-08-01

    Young men who have sex with men are at high risk for HIV, and most new HIV infections occur in serious relationships. This pilot study assessed the feasibility, acceptability and preliminary efficacy of the 2GETHER couples-based HIV prevention and relationship education intervention for young same-sex male couples. We enrolled 57 young male couples (N = 114) into a four-session hybrid group and individual intervention. We assessed acceptability via post-session surveys and exit interviews, and we examined preliminary efficacy at a two week posttest. The vast majority of participants (93%) reported exclusively positive impressions of 2GETHER, and all components received high mean ratings. We observed decreases in HIV risk behavior, increases in information, motivation and behavioral skills related to HIV prevention, and improvement in relationship investment between pretest and posttest. Integrating relationship education and sexual health programming may be an effective way to reduce HIV transmissions in young male couples.

  13. μ-opioid modulation of HIV-1 coreceptor expressionand HIV-1 replication

    International Nuclear Information System (INIS)

    Steele, Amber D.; Henderson, Earl E.; Rogers, Thomas J.

    2003-01-01

    A substantial proportion of HIV-1-infected individuals are intravenous drug users (IVDUs) who abuse opiates. Opioids induce a number of immunomodulatory effects that may directly influence HIV-1 disease progression. In the present report, we have investigated the effect of opioids on the expression of the major HIV-1 coreceptors CXCR4 and CCR5. For these studies we have focused on opiates which are ligands for the μ-opioid receptor. Our results show that DAMGO, a selective μ-opioid agonist, increases CXCR4 and CCR5 expression in both CD3 + lymphoblasts and CD14 + monocytes three- to fivefold. Furthermore, DAMGO-induced elevation of HIV-1 coreceptor expression translates into enhanced replication of both X4 and R5 viral strains of HIV-1. We have confirmed the role of the μ-opioid receptor based on the ability of a μ-opioid receptor-selective antagonist to block the effects of DAMGO. We have also found that morphine enhances CXCR4 and CCR5 expression and subsequently increases both X4 and R5 HIV-1 infection. We suggest that the capacity of μ-opioids to increase HIV-1 coreceptor expression and replication may promote viral binding, trafficking of HIV-1-infected cells, and enhanced disease progression

  14. Promotion of couples' voluntary counselling and testing for HIV through influential networks in two African capital cities

    Directory of Open Access Journals (Sweden)

    Bekan Brigitte

    2007-12-01

    Full Text Available Abstract Background Most new HIV infections in Africa are acquired from cohabiting heterosexual partners. Couples' Voluntary Counselling and Testing (CVCT is an effective prevention strategy for this group. We present our experience with a community-based program for the promotion of CVCT in Kigali, Rwanda and Lusaka, Zambia. Methods Influence Network Agents (INAs from the health, religious, non-governmental, and private sectors were trained to invite couples for CVCT. Predictors of successful promotion were identified using a multi-level hierarchical analysis. Results In 4 months, 9,900 invitations were distributed by 61 INAs, with 1,411 (14.3% couples requesting CVCT. INAs in Rwanda distributed fewer invitations (2,680 vs. 7,220 and had higher response rates (26.9% vs. 9.6%, than INAs in Zambia. Context of the invitation event, including a discreet location such as the INA's home (OR 3.3–3.4, delivery of the invitation to both partners in the couple (OR 1.6–1.7 or to someone known to the INA (OR 1.7–1.8, and use of public endorsement (OR 1.7–1.8 were stronger predictors of success than INA or couple-level characteristics. Conclusion Predictors of successful CVCT promotion included strategies that can be easily implemented in Africa. As new resources become available for Africans with HIV, CVCT should be broadly implemented as a point of entry for prevention, care and support.

  15. Immune defence against HIV-1 infection in HIV-1-exposed seronegative persons.

    Science.gov (United States)

    Schmechel, S C; Russell, N; Hladik, F; Lang, J; Wilson, A; Ha, R; Desbien, A; McElrath, M J

    2001-11-01

    Rare individuals who are repeatedly exposed to HIV-1 through unprotected sexual contact fail to acquire HIV-1 infection. These persons represent a unique study population to evaluate mechanisms by which HIV-1 replication is either prevented or controlled. We followed longitudinally a group of healthy HIV-1 seronegative persons each reporting repeated high-risk sexual activities with their HIV-1-infected partner at enrollment. The volunteers were primarily (90%) male homosexuals, maintaining high risk activities with their known infected partner (45%) or multiple other partners (61%). We evaluated the quantity and specificity of HIV-1-specific T cells in 31 exposed seronegatives (ES) using a IFN-gamma ELISPOT assay to enumerate T cells recognizing epitopes within HIV-1 Env, Gag, Pol and Nef. PBMC from only three of the 31 volunteers demonstrated ex vivo HIV-1-specific IFN-gamma secretion, in contrast to nearly 30% exhibiting cytolytic responses in previous studies. These findings suggest that if T cell responses in ES are induced by HIV-1 exposure, the frequency is at low levels in most of them, and below the level of detection using the ELISPOT assay. Alternative approaches to improve the sensitivity of detection may include use of dendritic cells as antigen-presenting cells in the ex vivo assay and more careful definition of the risk behavior and extent of HIV-1 exposure in conjunction with the evaluation of T cell responses.

  16. Synthesis and Anti-HIV-1 Evaluation of New Sonogashira-Modified Emivirine (MKC-442) Analogues

    DEFF Research Database (Denmark)

    Danel, Krzystof; Jørgensen, Per Trolle; La Colla, Paolo

    2009-01-01

    The MKC-442 analogue 6-(3,5-dimethylbenzyl)-5-ethyluracil substituted with a (propargyloxo)methyl group at N(1) has previously been found highly active against HIV-1. The C C bond in the substituent at N(1) is here utilized in a series of chemical reactions in order to develop new agents with hig......The MKC-442 analogue 6-(3,5-dimethylbenzyl)-5-ethyluracil substituted with a (propargyloxo)methyl group at N(1) has previously been found highly active against HIV-1. The C C bond in the substituent at N(1) is here utilized in a series of chemical reactions in order to develop new agents...... with higher activity against HIV-1-resistant mutants. The syntheses involved Pd-catalyzed C,C-coupling reactions, addition of disulfides, and click chemistry on the terminal C C bond as well as addition of bromine to the so formed internal C C bonds. Sonogashira coupling were performed with silyl...

  17. Power and the association with relationship quality in South African couples: Implications for HIV/AIDS interventions.

    Science.gov (United States)

    Conroy, Amy A; McGrath, Nuala; van Rooyen, Heidi; Hosegood, Victoria; Johnson, Mallory O; Fritz, Katherine; Marr, Alexander; Ngubane, Thulani; Darbes, Lynae A

    2016-03-01

    Power imbalances within sexual relationships have significant implications for HIV prevention in sub-Saharan Africa. Little is known about how power influences the quality of a relationship, which could be an important pathway leading to healthy behavior around HIV/AIDS. This paper uses data from 448 heterosexual couples (896 individuals) in rural KwaZulu-Natal, South Africa who completed baseline surveys from 2012 to 2014 as part of a couples-based HIV intervention trial. Using an actor-partner interdependence perspective, we assessed: (1) how both partners' perceptions of power influences their own (i.e., actor effect) and their partner's reports of relationship quality (i.e., partner effect); and (2) whether these associations differed by gender. We examined three constructs related to power (female power, male equitable gender norms, and shared power) and four domains of relationship quality (intimacy, trust, mutually constructive communication, and conflict). For actor effects, shared power was strongly and consistently associated with higher relationship quality across all four domains. The effect of shared power on trust, mutually constructive communication, and conflict were stronger for men than women. The findings for female power and male equitable gender norms were more mixed. Female power was positively associated with women's reports of trust and mutually constructive communication, but negatively associated with intimacy. Male equitable gender norms were positively associated with men's reports of mutually constructive communication. For partner effects, male equitable gender norms were positively associated with women's reports of intimacy and negatively associated with women's reports of conflict. Research and health interventions aiming to improving HIV-related behaviors should consider sources of shared power within couples and potential leverage points for empowerment at the couple level. Efforts solely focused on empowering women should also

  18. Power and the Association with Relationship Quality in South African Couples: Implications for HIV/AIDS Interventions

    Science.gov (United States)

    Conroy, Amy A.; McGrath, Nuala; van Rooyen, Heidi; Hosegood, Victoria; Johnson, Mallory O.; Fritz, Katherine; Marr, Alexander; Ngubane, Thulani; Darbes, Lynae A.

    2016-01-01

    Introduction Power imbalances within sexual relationships have significant implications for HIV prevention in sub-Saharan Africa. Little is known about how power influences the quality of a relationship, which could be an important pathway leading to healthy behavior around HIV/AIDS. Methods This paper uses data from 448 heterosexual couples (896 individuals) in rural KwaZulu-Natal, South Africa who completed baseline surveys from 2012–2014 as part of a couples-based HIV intervention trial. Using an actor-partner interdependence perspective, we assessed: (1) how both partners’ perceptions of power influences their own (i.e., actor effect) and their partner’s reports of relationship quality (i.e., partner effect); and (2) whether these associations differed by gender. We examined three constructs related to power (female power, male equitable gender norms, and shared power) and four domains of relationship quality (intimacy, trust, mutually constructive communication, and conflict). Results For actor effects, shared power was strongly and consistently associated with higher relationship quality across all four domains. The effect of shared power on trust, mutually constructive communication, and conflict were stronger for men than women. The findings for female power and male equitable gender norms were more mixed. Female power was positively associated with women’s reports of trust and mutually constructive communication, but negatively associated with intimacy. Male equitable gender norms were positively associated with men’s reports of mutually constructive communication. For partner effects, male equitable gender norms were positively associated with women’s reports of intimacy and negatively associated with women’s reports of conflict. Conclusions Research and health interventions aiming to improving HIV-related behaviors should consider sources of shared power within couples and potential leverage points for empowerment at the couple level

  19. Interdependence of Inhibitor Recognition in HIV-1 Protease.

    Science.gov (United States)

    Paulsen, Janet L; Leidner, Florian; Ragland, Debra A; Kurt Yilmaz, Nese; Schiffer, Celia A

    2017-05-09

    Molecular recognition is a highly interdependent process. Subsite couplings within the active site of proteases are most often revealed through conditional amino acid preferences in substrate recognition. However, the potential effect of these couplings on inhibition and thus inhibitor design is largely unexplored. The present study examines the interdependency of subsites in HIV-1 protease using a focused library of protease inhibitors, to aid in future inhibitor design. Previously a series of darunavir (DRV) analogs was designed to systematically probe the S1' and S2' subsites. Co-crystal structures of these analogs with HIV-1 protease provide the ideal opportunity to probe subsite interdependency. All-atom molecular dynamics simulations starting from these structures were performed and systematically analyzed in terms of atomic fluctuations, intermolecular interactions, and water structure. These analyses reveal that the S1' subsite highly influences other subsites: the extension of the hydrophobic P1' moiety results in 1) reduced van der Waals contacts in the P2' subsite, 2) more variability in the hydrogen bond frequencies with catalytic residues and the flap water, and 3) changes in the occupancy of conserved water sites both proximal and distal to the active site. In addition, one of the monomers in this homodimeric enzyme has atomic fluctuations more highly correlated with DRV than the other monomer. These relationships intricately link the HIV-1 protease subsites and are critical to understanding molecular recognition and inhibitor binding. More broadly, the interdependency of subsite recognition within an active site requires consideration in the selection of chemical moieties in drug design; this strategy is in contrast to what is traditionally done with independent optimization of chemical moieties of an inhibitor.

  20. Pilot study of home-based delivery of HIV testing and counseling and contraceptive services to couples in Malawi.

    Science.gov (United States)

    Becker, Stan; Taulo, Frank O; Hindin, Michelle J; Chipeta, Effie K; Loll, Dana; Tsui, Amy

    2014-12-20

    HIV counseling and testing for couples is an important component of HIV prevention strategies, particularly in Sub Saharan Africa. The purpose of this pilot study is to estimate the uptake of couple HIV counseling and testing (CHCT) and couple family planning (CFP) services in a single home visit in peri-urban Malawi and to assess related factors. This study involved offering CHCT and CFP services to couples in their homes; 180 couples were sampled from households in a peri-urban area of Blantyre. Baseline data were collected from both partners and follow-up data were collected one week later. A pair of male and female counselors approached each partner separately about HIV testing and counseling and contraceptive services and then, if both consented, CHCT and CFP services (pills, condoms and referrals for other methods) were given. Bivariate and multivariate logistic regression analyses were done to examine the relationship between individual partner characteristics and acceptance of the services. Selected behaviors reported pre- and post-intervention, particularly couple reports on contraceptive use and condom use at last sex, were also tested for differences. 89% of couples accepted at least one of the services (58% CHCT-only, 29% CHCT + CFP, 2% CFP-only). Among women, prior testing experience (p emotional closeness to partner (p contraceptive services to prevent the undesired consequences of sexually transmitted infection and unintended pregnancy via unprotected sex.

  1. Negotiating sexual safety in the era of biomedical HIV prevention: relationship dynamics among male couples using pre-exposure prophylaxis.

    Science.gov (United States)

    Malone, Jowanna; Syvertsen, Jennifer L; Johnson, Blake E; Mimiaga, Matthew J; Mayer, Kenneth H; Bazzi, Angela R

    2018-06-01

    Up to two-thirds of new cases of HIV transmission between gay, bisexual and other men who have sex with men in the USA are attributed to primary relationships. Understanding the relationship dynamics and sexual agreements of male-male couples can provide insight into HIV transmission patterns and prevention needs in this population. The daily use of antiretroviral pre-exposure prophylaxis (PrEP) is highly effective in preventing HIV, but its negotiation and use within social and intimate relationship contexts remain understudied. We conducted semi-structured qualitative interviews with 20 male couples (n = 40 men) in which at least one partner was either using or in the process of initiating PrEP. Congruent with a theoretical focus on social theories of relationships and negotiated risk, couples were interviewed about relationship dynamics, trust, communication and sexual health practices, including their perception and use of PrEP. Overall, we found that couples showed heightened trust and communication when establishing open, sexual agreements and demonstrated high awareness of sexual risks and health practices in the context of PrEP use. This study demonstrates how understanding relationship dynamics can better inform HIV prevention and sexual health promotion efforts for male couples at risk of HIV.

  2. Contraceptive discontinuation and switching among couples receiving integrated HIV and family planning services in Lusaka, Zambia.

    Science.gov (United States)

    Haddad, Lisa; Wall, Kristin M; Vwalika, Bellington; Khu, Naw Htee; Brill, Ilene; Kilembe, William; Stephenson, Rob; Chomba, Elwyn; Vwalika, Cheswa; Tichacek, Amanda; Allen, Susan

    2013-10-01

    To describe predictors of contraceptive method discontinuation and switching behaviours among HIV-positive couples receiving couples' voluntary HIV counselling and testing services in Lusaka, Zambia. Couples were randomized in a factorial design to two-family planning educational intervention videos, received comprehensive family planning services and were assessed every 3 months for contraceptive initiation, discontinuation and switching. We modelled factors associated with contraceptive method upgrading and downgrading via multivariate Andersen-Gill models. Most women continued the initial method selected after randomization. The highest rates of discontinuation/switching were observed for injectable contraceptive and intrauterine device users. Time to discontinuing the more effective contraceptive methods or downgrading to oral contraceptives or condoms was associated with the women's younger age, desire for more children within the next year, heavy menstrual bleeding, bleeding between periods and cystitis/dysuria. Health concerns among women about contraceptive implants and male partners not wanting more children were associated with upgrading from oral contraceptives or condoms. HIV status of the woman or the couple was not predictive of switching or stopping. We found complicated patterns of contraceptive use. The predictors of contraception switching indicate that interventions targeted to younger couples that address common contraception-related misconceptions could improve effective family planning utilization. We recommend these findings be used to increase the uptake and continuation of contraception, especially long-acting reversible contraceptive (LARC) methods, and that fertility goal based, LARC-focused family planning be offered as an integral part of HIV prevention services.

  3. Seroadaptive Behaviors of Men Who Have Sex with Men in Myanmar.

    Science.gov (United States)

    Aung, Tin; Thein, Si Thu; McFarland, Willi

    2016-12-01

    Serosorting (i.e., choosing partners of the same HIV serostatus to reduce the risk of transmission with unprotected sex) and other forms of seroadaptation (i.e., engaging in diverse behaviors according to a hierarchy of risk by type of sex and partner serostatus) are phenomena widely described for men who have sex with men (MSM) in the developed world. We assessed seroadaptive behaviors among MSM surveyed in Yangon, Myanmar in 2013-2014. Among HIV-negative MSM, 43.1 % engaged in some form seroadaptation including serosorting (21.8 %), using condoms with potentially serodiscordant anal sex (19.3 %), and seropositioning (1.7 %). Among HIV-positive MSM, 3.5 % engaged in serosorting, 36.0 % in using condoms with potentially serodiscordant anal sex, 7.0 % in seropositioning, and 46.5 % in any form of seroadaptation. For HIV-negative and HIV-positive MSM, seroadaptation was more common than consistent condom use (38.0 and 26.7 %, respectively). MSM in Myanmar are engaging in seroadaptive behaviors in magnitude and ways similar to MSM in industrialized countries.

  4. Gender-based power and couples' HIV risk in Uttar Pradesh and Uttarakhand, north India.

    Science.gov (United States)

    Agrawal, Alpna; Bloom, Shelah S; Suchindran, Chirayath; Curtis, Siân; Angeles, Gustavo

    2014-12-01

    Gender inequality is a long-recognized driver of the HIV epidemic. However, few studies have investigated the association between gender-based power and HIV risk in India, which has the world's third largest HIV epidemic. Population-based data collected in 2003 from 3,385 couples residing in Uttar Pradesh and Uttarakhand, North India, were used to examine associations between gender-based power (wife's autonomy and husband's inequitable gender attitudes) and indicators of couples' HIV risk (whether the husband had had premarital sex with someone other than his eventual spouse, extramarital sex in the past year or STI symptoms in the past year). Structural equation modeling was used to create composite variables for the gender-based power measures and test their associations with HIV risk measures. Twenty-four percent of husbands had had premarital sex, 7% had had extramarital sex in the past year and 6% had had STI symptoms in the past year. Structural equation models indicated that wives who reported higher levels of autonomy were less likely than other wives to have husbands who had had extramarital sex in the past year (direct association) or STI symptoms in the past year (indirect association). Moreover, husbands who endorsed more inequitable gender attitudes were more likely than others to report having had premarital sex with someone other than their spouse, which in turn was associated with having had extramarital sex and STI symptoms in the past year. If the associations identified in this study reflect a causal relationship between gender-based power and HIV risk behavior, then HIV prevention programs that successfully address inequitable gender roles may reduce HIV risks in North India.

  5. Influenza vaccination of HIV-1-positive and HIV-1-negative former intravenous drug users.

    Science.gov (United States)

    Amendola, A; Boschini, A; Colzani, D; Anselmi, G; Oltolina, A; Zucconi, R; Begnini, M; Besana, S; Tanzi, E; Zanetti, A R

    2001-12-01

    The immunogenicity of an anti-influenza vaccine was assessed in 409 former intravenous drug user volunteers and its effect on the levels of HIV-1 RNA, proviral DNA and on CD4+ lymphocyte counts in a subset HIV-1-positive subjects was measured. HIV-1-positive individuals (n = 72) were divided into three groups on the basis of their CD4+ lymphocyte counts, while the 337 HIV-1-negative participants were allocated into group four. Haemagglutination inhibiting (HI) responses varied from 45.8 to 70% in the HIV-1-positive subjects and were significantly higher in group four (80.7% responses to the H1N1 strain, 81.6% to the H3N2 strain, and 83% to the B strain). The percentage of subjects with HI protective antibody titres (> or = 1:40) increased significantly after vaccination, especially in HIV-1 uninfected subjects. Immunization caused no significant changes in CD4+ counts and in neither plasma HIV-1 RNA nor proviral DNA levels. Therefore, vaccination against influenza may benefit persons infected by HIV-1. Copyright 2001 Wiley-Liss, Inc.

  6. Label-free detection of HIV-1 infected cells via integration of optical tweezers and photoluminescence spectroscopy

    Science.gov (United States)

    Lugongolo, Masixole Yvonne; Ombinda-Lemboumba, Saturnin; Noto, Luyanda Lunga; Maaza, Malik; Mthunzi-Kufa, Patience

    2018-02-01

    The human immunodeficiency virus-1 (HIV-1) is currently detected using conventional qualitative and quantitative tests to determine the presence or absence of HIV in blood samples. However, the approach of these tests detects the presence of either viral antibodies or viral RNA that require labelling which may be costly, sophisticated and time consuming. A label-free approach of detecting the presence of HIV is therefore desirable. Of note optical tweezers can be coupled with other technologies including spectroscopy, which also investigates light-matter interactions. For example, coupling of optical tweezers with luminescence spectroscopy techniques has emerged as a powerful tool in biology for micro-manipulation, detection and analysis of individual cells. Integration of optical techniques has enabled studying biological particles in a label-free manner, whilst detecting functional groups and other essential molecules within mixed populations of cells. In the current study, an optical trapping system coupled to luminescence spectroscopy was utilised to detect the presence of HIV infection in TZM-bl cells in vitro. This was performed by infecting TZM-bl cells with the ZM53 HIV-1 pseudovirus, and incubating them for 48 hours prior analysis. The differences between infected and uninfected cells were thereafter displayed as shown by the spectrographs obtained. Combination of these two techniques has a potential in the field of infectious disease diagnostics.

  7. Semen Bacterial Concentrations and HIV-1 RNA Shedding Among HIV-1-Seropositive Kenyan Men.

    Science.gov (United States)

    Korhonen, Christine J; Srinivasan, Sujatha; Huang, Dandi; Ko, Daisy L; Sanders, Eduard J; Peshu, Norbert M; Krieger, John N; Muller, Charles H; Coombs, Robert W; Fredricks, David N; Graham, Susan M

    2017-03-01

    HIV-1 is transmitted through semen from men to their sexual partners. Genital infections can increase HIV-1 RNA shedding in semen, but shedding also occurs in the absence of typical pathogens. We hypothesized that higher bacterial concentrations in semen would be associated with higher HIV-1 RNA levels. We analyzed semen samples from 42 HIV-1-seropositive Kenyan men using quantitative polymerase chain reaction (PCR) to assess bacterial concentrations and real-time PCR to measure HIV-1 RNA levels. Generalized estimation equations were used to evaluate associations between these 2 measures. Broad-range 16S rRNA gene PCR with pyrosequencing was performed on a subset of 13 samples to assess bacterial community composition. Bacteria were detected in 96.6% of 88 samples by quantitative PCR. Semen bacterial concentration and HIV-1 RNA levels were correlated 0.30 (P = 0.01). The association between bacterial concentration and HIV-1 RNA detection was not significant after adjustment for antiretroviral therapy (ART) (adjusted odds ratio: 1.27, 95% CI: 0.84 to 1.91). Factors associated with semen bacterial concentration included insertive anal sex (adjusted beta 0.92, 95% CI: 0.12 to 1.73) and ART use (adjusted beta: -0.77, 95% CI: -1.50 to 0.04). Among 13 samples with pyrosequencing data, Corynebacterium spp., Staphylococcus spp., and Streptococcus spp. were most frequently detected. Most of these HIV-1-infected men had bacteria in their semen. ART use was associated with undetectable semen HIV-1 RNA and lower semen bacterial concentrations, whereas insertive anal sex was associated with higher bacterial concentrations. Additional studies evaluating the relationship between semen bacteria, inflammation, mucosal immunity, and HIV-1 shedding are needed to understand implications for HIV-1 transmission.

  8. HIV-1 molecular epidemiology among newly diagnosed HIV-1 individuals in Hebei, a low HIV prevalence province in China.

    Science.gov (United States)

    Lu, Xinli; Kang, Xianjiang; Liu, Yongjian; Cui, Ze; Guo, Wei; Zhao, Cuiying; Li, Yan; Chen, Suliang; Li, Jingyun; Zhang, Yuqi; Zhao, Hongru

    2017-01-01

    New human immunodeficiency virus type 1 (HIV-1) diagnoses are increasing rapidly in Hebei. The aim of this study presents the most extensive HIV-1 molecular epidemiology investigation in Hebei province in China thus far. We have carried out the most extensive systematic cross-sectional study based on newly diagnosed HIV-1 positive individuals in 2013, and characterized the molecular epidemiology of HIV-1 based on full length gag-partial pol gene sequences in the whole of Hebei. Nine HIV-1 genotypes based on full length gag-partial pol gene sequence were identified among 610 newly diagnosed naïve individuals. The four main genotypes were circulating recombinant form (CRF)01_AE (53.4%), CRF07_BC (23.4%), subtype B (15.9%), and unique recombinant forms URFs (4.9%). Within 1 year, three new genotypes (subtype A1, CRF55_01B, CRF65_cpx), unknown before in Hebei, were first found among men who have sex with men (MSM). All nine genotypes were identified in the sexually contracted HIV-1 population. Among 30 URFs, six recombinant patterns were revealed, including CRF01_AE/BC (40.0%), CRF01_AE/B (23.3%), B/C (16.7%), CRF01_AE/C (13.3%), CRF01_AE/B/A2 (3.3%) and CRF01_AE/BC/A2 (3.3%), plus two potential CRFs. This study elucidated the complicated characteristics of HIV-1 molecular epidemiology in a low HIV-1 prevalence northern province of China and revealed the high level of HIV-1 genetic diversity. All nine HIV-1 genotypes circulating in Hebei have spread out of their initial risk groups into the general population through sexual contact, especially through MSM. This highlights the urgency of HIV prevention and control in China.

  9. HIV-1 molecular epidemiology among newly diagnosed HIV-1 individuals in Hebei, a low HIV prevalence province in China.

    Directory of Open Access Journals (Sweden)

    Xinli Lu

    Full Text Available New human immunodeficiency virus type 1 (HIV-1 diagnoses are increasing rapidly in Hebei. The aim of this study presents the most extensive HIV-1 molecular epidemiology investigation in Hebei province in China thus far. We have carried out the most extensive systematic cross-sectional study based on newly diagnosed HIV-1 positive individuals in 2013, and characterized the molecular epidemiology of HIV-1 based on full length gag-partial pol gene sequences in the whole of Hebei. Nine HIV-1 genotypes based on full length gag-partial pol gene sequence were identified among 610 newly diagnosed naïve individuals. The four main genotypes were circulating recombinant form (CRF01_AE (53.4%, CRF07_BC (23.4%, subtype B (15.9%, and unique recombinant forms URFs (4.9%. Within 1 year, three new genotypes (subtype A1, CRF55_01B, CRF65_cpx, unknown before in Hebei, were first found among men who have sex with men (MSM. All nine genotypes were identified in the sexually contracted HIV-1 population. Among 30 URFs, six recombinant patterns were revealed, including CRF01_AE/BC (40.0%, CRF01_AE/B (23.3%, B/C (16.7%, CRF01_AE/C (13.3%, CRF01_AE/B/A2 (3.3% and CRF01_AE/BC/A2 (3.3%, plus two potential CRFs. This study elucidated the complicated characteristics of HIV-1 molecular epidemiology in a low HIV-1 prevalence northern province of China and revealed the high level of HIV-1 genetic diversity. All nine HIV-1 genotypes circulating in Hebei have spread out of their initial risk groups into the general population through sexual contact, especially through MSM. This highlights the urgency of HIV prevention and control in China.

  10. A discussion of key values to inform the design and delivery of services for HIV-affected women and couples attempting pregnancy in resource-constrained settings.

    Science.gov (United States)

    Heffron, Renee; Davies, Natasha; Cooke, Ian; Kaida, Angela; Mergler, Reid; van der Poel, Sheryl; Cohen, Craig R; Mmeje, Okeoma

    2015-01-01

    HIV-affected women and couples often desire children and many accept HIV risk in order to attempt pregnancy and satisfy goals for a family. Risk reduction strategies to mitigate sexual and perinatal HIV transmission include biomedical and behavioural approaches. Current efforts to integrate HIV and reproductive health services offer prime opportunities to incorporate strategies for HIV risk reduction during pregnancy attempts. Key client and provider values about services to optimize pregnancy in the context of HIV risk provide insights for the design and implementation of large-scale "safer conception" programmes. Through our collective experience and discussions at a multi-disciplinary international World Health Organization-convened workshop to initiate the development of guidelines and an algorithm of care to support the delivery of services for HIV-affected women and couples attempting pregnancy, we identified four values that are key to the implementation of these programmes: (1) understanding fertility care and an ability to identify potential fertility problems; (2) providing equity of access to resources enabling informed decision-making about reproductive choices; (3) creating enabling environments that reduce stigma associated with HIV and infertility; and (4) creating enabling environments that encourage disclosure of HIV status and fertility status to partners. Based on these values, recommendations for programmes serving HIV-affected women and couples attempting pregnancy include the following: incorporation of comprehensive reproductive health counselling; training to support the transfer and exchange of knowledge between providers and clients; care environments that reduce the stigma of childbearing among HIV-affected women and couples; support for safe and voluntary disclosure of HIV and fertility status; and increased efforts to engage men in reproductive decision-making at times that align with women's desires. Programmes, policies and guidelines

  11. Community Cultural Norms, Stigma and Disclosure to Sexual Partners among Women Living with HIV in Thailand, Brazil and Zambia (HPTN 063.

    Directory of Open Access Journals (Sweden)

    Bisola O Ojikutu

    Full Text Available Serostatus disclosure may facilitate decreased HIV transmission between serodiscordant partners by raising risk awareness and heightening the need for prevention. For women living with HIV (WLWH, the decision to disclose may be influenced by culturally determined, community-level stigma and norms. Understanding the impact of community HIV stigma and gender norms on disclosure among WLWH in different countries may inform intervention development.HPTN063 was a longitudinal, observational study of sexually active HIV-infected individuals, including heterosexual women, in care in Zambia, Thailand and Brazil. At baseline, a questionnaire measuring community HIV stigma and gender norms, anticipated stigma, demographic, partner/relationship characteristics, and intimate partner violence was administered. Longitudinal HIV disclosure to sexual partners was determined via audio-computer assisted self-interview (ACASI at the baseline and quarterly during the one year following up. Logistic regression was conducted to identify the predictors of disclosure.Almost half (45% of women living with HIV acknowledged perceived community HIV stigma (the belief that in their community HIV infection among women is associated with sex work and multiple sexual partners. Many women (42.9% also acknowledged perceived community gender norms (the belief that traditional gender norms such as submissiveness to husbands/male sexual partners is necessary and that social status is lost if one does not procreate. HIV disclosure to current sex partners was reported by 67% of women. In multivariate analysis, among all women, those who were older [OR 0.16, 95%CI(0.06,0.48], reported symptoms of severe depression [OR 0.53, 95%CI(0.31, 0.90], endorsed anticipated stigma [OR 0.30, 95%CI(0.18, 0.50], and were unmarried [OR 0.43, 95%CI(0.26,0.71] were less likely to disclose to current partners. In an analysis stratified by marital status and cohabitation, unmarried [OR 0.41, 95%CI(0

  12. HIV-1 vaccines

    Science.gov (United States)

    Excler, Jean-Louis; Robb, Merlin L; Kim, Jerome H

    2014-01-01

    The development of a safe and effective preventive HIV-1 vaccine remains a public health priority. Despite scientific difficulties and disappointing results, HIV-1 vaccine clinical development has, for the first time, established proof-of-concept efficacy against HIV-1 acquisition and identified vaccine-associated immune correlates of risk. The correlate of risk analysis showed that IgG antibodies against the gp120 V2 loop correlated with decreased risk of HIV infection, while Env-specific IgA directly correlated with increased risk. The development of vaccine strategies such as improved envelope proteins formulated with potent adjuvants and DNA and vectors expressing mosaics, or conserved sequences, capable of eliciting greater breadth and depth of potentially relevant immune responses including neutralizing and non-neutralizing antibodies, CD4+ and CD8+ cell-mediated immune responses, mucosal immune responses, and immunological memory, is now proceeding quickly. Additional human efficacy trials combined with other prevention modalities along with sustained funding and international collaboration remain key to bring an HIV-1 vaccine to licensure. PMID:24637946

  13. Mistrust in marriage-Reasons why men do not accept couple HIV testing during antenatal care- a qualitative study in eastern Uganda

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    Popenoe Rebecca

    2010-12-01

    Full Text Available Abstract Background A policy for couple HIV counseling and testing was introduced in 2006 in Uganda, urging pregnant women and their spouses to be HIV tested together during antenatal care (ANC. The policy aims to identify HIV-infected pregnant women to prevent mother-to-child transmission of HIV through prophylactic antiretroviral treatment, to provide counseling, and to link HIV-infected persons to care. However, the uptake of couple testing remains low. This study explores men's views on, and experiences of couple HIV testing during ANC. Methods The study was conducted at two time points, in 2008 and 2009, in the rural Iganga and Mayuge districts of eastern Uganda. We carried out nine focus group discussions, about 10 participants in each, and in-depth interviews with 13 men, all of whom were fathers. Data were collected in the local language, Lusoga, audio-recorded and thereafter translated and transcribed into English and analyzed using content analysis. Results Men were fully aware of the availability of couple HIV testing, but cited several barriers to their use of these services. The men perceived their marriages as unstable and distrustful, making the idea of couple testing unappealing because of the conflicts it could give rise to. Further, they did not understand why they should be tested if they did not have symptoms. Finally, the perceived stigmatizing nature of HIV care and rude attitudes among health workers at the health facilities led them to view the health facilities providing ANC as unwelcoming. The men in our study had several suggestions for how to improve the current policy: peer sensitization of men, make health facilities less stigmatizing and more male-friendly, train health workers to meet men's needs, and hold discussions between health workers and community members. Conclusions In summary, pursuing couple HIV testing as a main avenue for making men more willing to test and support PMTCT for their wives, does not seem

  14. Macrophage Resistance to HIV-1 Infection Is Enhanced by the Neuropeptides VIP and PACAP

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    Temerozo, Jairo R.; Joaquim, Rafael; Regis, Eduardo G.; Savino, Wilson; Bou-Habib, Dumith Chequer

    2013-01-01

    It is well established that host factors can modulate HIV-1 replication in macrophages, critical cells in the pathogenesis of HIV-1 infection due to their ability to continuously produce virus. The neuropeptides VIP and PACAP induce well-characterized effects on macrophages through binding to the G protein-coupled receptors VPAC1, VPAC2 and PAC1, but their influence on HIV-1 production by these cells has not been established. Here, we describe that VIP and PACAP reduce macrophage production of HIV-1, acting in a synergistic or additive manner to decrease viral growth. Using receptor antagonists, we detected that the HIV-1 inhibition promoted by VIP is dependent on its ligation to VPAC1/2, whereas PACAP decreases HIV-1 growth via activation of the VPAC1/2 and PAC1 receptors. Specific agonists of VPAC2 or PAC1 decrease macrophage production of HIV-1, whereas sole activation of VPAC1 enhances viral growth. However, the combination of specific agonists mimicking the receptor preference of the natural neuropeptides reproduces the ability of VIP and PACAP to increase macrophage resistance to HIV-1 replication. VIP and PACAP up-regulated macrophage secretion of the β-chemokines CCL3 and CCL5 and the cytokine IL-10, whose neutralization reversed the neuropeptide-induced inhibition of HIV-1 replication. Our results suggest that VIP and PACAP and the receptors VPAC2 and PAC1 could be used as targets for developing alternative therapeutic strategies for HIV-1 infection. PMID:23818986

  15. A Conceptual Model of Dyadic Coordination in HIV Care Engagement Among Couples of Black Men Who Have Sex with Men: A Qualitative Dyadic Analysis.

    Science.gov (United States)

    Tan, Judy Y; Campbell, Chadwick K; Tabrisky, Alyssa P; Siedle-Khan, Robert; Conroy, Amy A

    2018-02-20

    Among Black men who have sex with men (MSM), HIV incidence is disproportionately high and HIV care engagement is disproportionately low. There may be important opportunities to leverage the primary relationship to improve engagement in HIV care and treatment among Black MSM couples. Using dyadic qualitative analysis of semi-structured, one-on-one interviews, we explored dyadic aspects of HIV care engagement among 14 Black MSM couples in which at least one partner was HIV-positive and identified as a Black cisgender man. Findings showed that men varied in how involved they were in their HIV-positive partner's care and treatment, and in how they reciprocated their partner's involvement. Patterns of dyadic HIV care engagement supported a conceptual model of dyadic coordination that describes Black MSM relationships in terms of two conceptual dimensions of dyadic HIV care engagement, and guides future intervention designs with Black MSM couples.

  16. Trans-dissemination of exosomes from HIV-1-infected cells fosters both HIV-1 trans-infection in resting CD4+ T lymphocytes and reactivation of the HIV-1 reservoir.

    Science.gov (United States)

    Chiozzini, Chiara; Arenaccio, Claudia; Olivetta, Eleonora; Anticoli, Simona; Manfredi, Francesco; Ferrantelli, Flavia; d'Ettorre, Gabriella; Schietroma, Ivan; Andreotti, Mauro; Federico, Maurizio

    2017-09-01

    Intact HIV-1 and exosomes can be internalized by dendritic cells (DCs) through a common pathway leading to their transmission to CD4 + T lymphocytes by means of mechanisms defined as trans-infection and trans-dissemination, respectively. We previously reported that exosomes from HIV-1-infected cells activate both uninfected quiescent CD4 + T lymphocytes, which become permissive to HIV-1, and latently infected cells, with release of HIV-1 particles. However, nothing is known about the effects of trans-dissemination of exosomes produced by HIV-1-infected cells on uninfected or latently HIV-1-infected CD4 + T lymphocytes. Here, we report that trans-dissemination of exosomes from HIV-1-infected cells induces cell activation in resting CD4 + T lymphocytes, which appears stronger with mature than immature DCs. Using purified preparations of both HIV-1 and exosomes, we observed that mDC-mediated trans-dissemination of exosomes from HIV-1-infected cells to resting CD4 + T lymphocytes induces efficient trans-infection and HIV-1 expression in target cells. Most relevant, when both mDCs and CD4 + T lymphocytes were isolated from combination anti-retroviral therapy (ART)-treated HIV-1-infected patients, trans-dissemination of exosomes from HIV-1-infected cells led to HIV-1 reactivation from the viral reservoir. In sum, our data suggest a role of exosome trans-dissemination in both HIV-1 spread in the infected host and reactivation of the HIV-1 reservoir.

  17. Couple-level Motivations to Test for HIV for Gay Men in Relationships

    Science.gov (United States)

    Beougher, Sean C.; Bircher, Anja E.; Chakravarty, Deepalika; Darbes, Lynae A.; Gómez Mandic, Carmen; Neilands, Torsten B.; Garcia, Carla C.; Hoff, Colleen C.

    2015-01-01

    Previous studies of HIV testing among gay men describe the motivations, facilitators and barriers, behaviors, and demographic characteristics of individuals who test. What little research focuses on HIV testing among gay men in relationships shows that they do not test regularly or, in some cases, at all – their motivations to test have not been investigated. With so little data on HIV testing for this population, and the continued privileging of individually-focused approaches, gay men in relationships fall into a blind spot of research and prevention efforts. This study examined motivations to test for HIV using qualitative data from both partners in 20 gay male couples. Analysis revealed that the partners’ motivations were either event-related (e.g., participants testing the beginning of their relationship or HIV-negative participants in an HIV-discordant relationship testing after risky episode with their discordant primary partner) or partner-related (e.g., participants testing in response to a request or suggestion to test from their primary partner or participants testing out of concern for their primary partner’s health and wellbeing). These data provide insight into relationship-oriented motivations to test for HIV for gay men in relationships and, in doing so, demonstrates their commitment to their primary partner and relationship. These motivations can be leveraged to increase HIV testing among gay men in relationships, a population that tests less often than single gay men, yet, until recently, has been underserved by prevention efforts. PMID:25550145

  18. Developing strategies for HIV-1 eradication

    Science.gov (United States)

    Durand, Christine M.; Blankson, Joel N.; Siliciano, Robert F.

    2014-01-01

    Highly active antiretroviral therapy (HAART) suppresses HIV-1 replication, transforming the outlook for infected patients. However, reservoirs of replication-competent forms of the virus persist during HAART, and when treatment is stopped, high rates of HIV-1 replication return. Recent insights into HIV-1 latency, as well as a report that HIV-1 infection was eradicated in one individual, have renewed interest in finding a cure for HIV-1 infection. Strategies for HIV-1 eradication include gene therapy and hematopoietic stem cell transplantation, stimulating host immunity to control HIV-1 replication, and targeting latent HIV-1 in resting memory CD4+ T cells. Future efforts should aim to provide better understanding of how to reconstitute the CD4+ T cell compartment with genetically engineered cells, exert immune control over HIV-1 replication, and identify and eliminate all viral reservoirs. PMID:22867874

  19. Semen Bacterial Concentrations and HIV-1 RNA Shedding Among HIV-1–Seropositive Kenyan Men

    Science.gov (United States)

    Srinivasan, Sujatha; Huang, Dandi; Ko, Daisy L.; Sanders, Eduard J.; Peshu, Norbert M.; Krieger, John N.; Muller, Charles H.; Coombs, Robert W.; Fredricks, David N.; Graham, Susan M.

    2017-01-01

    Introduction: HIV-1 is transmitted through semen from men to their sexual partners. Genital infections can increase HIV-1 RNA shedding in semen, but shedding also occurs in the absence of typical pathogens. We hypothesized that higher bacterial concentrations in semen would be associated with higher HIV-1 RNA levels. Methods: We analyzed semen samples from 42 HIV-1–seropositive Kenyan men using quantitative polymerase chain reaction (PCR) to assess bacterial concentrations and real-time PCR to measure HIV-1 RNA levels. Generalized estimation equations were used to evaluate associations between these 2 measures. Broad-range 16S rRNA gene PCR with pyrosequencing was performed on a subset of 13 samples to assess bacterial community composition. Results: Bacteria were detected in 96.6% of 88 samples by quantitative PCR. Semen bacterial concentration and HIV-1 RNA levels were correlated 0.30 (P = 0.01). The association between bacterial concentration and HIV-1 RNA detection was not significant after adjustment for antiretroviral therapy (ART) (adjusted odds ratio: 1.27, 95% CI: 0.84 to 1.91). Factors associated with semen bacterial concentration included insertive anal sex (adjusted beta 0.92, 95% CI: 0.12 to 1.73) and ART use (adjusted beta: −0.77, 95% CI: −1.50 to 0.04). Among 13 samples with pyrosequencing data, Corynebacterium spp., Staphylococcus spp., and Streptococcus spp. were most frequently detected. Conclusion: Most of these HIV-1–infected men had bacteria in their semen. ART use was associated with undetectable semen HIV-1 RNA and lower semen bacterial concentrations, whereas insertive anal sex was associated with higher bacterial concentrations. Additional studies evaluating the relationship between semen bacteria, inflammation, mucosal immunity, and HIV-1 shedding are needed to understand implications for HIV-1 transmission. PMID:27861240

  20. "I Do Not Take My Medicine while Hiding" - A Longitudinal Qualitative Assessment of HIV Discordant Couples' Beliefs in Discordance and ART as Prevention in Uganda.

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    Rachel King

    Full Text Available HIV negative members of serostatus discordant couples are at high risk for HIV acquisition, but few interventions are in place to target them in sub-Saharan Africa.In this study, we interviewed 28 couples, 3 times over a period of one year to understand their perceptions and attitudes around discordance, their relationship dynamics, their HIV risk behaviour, their beliefs and attitudes about antiretroviral therapy (ART and their views of the community perceptions of discordance and treatment for HIV.Findings revealed that at baseline there were multiple complex explanations and interpretations about discordance among discordant couples and their surrounding community. Shifts in beliefs and attitudes about discordance, HIV risk reduction and ART over time were enabled through re-testing negative members of discordant couples and repeat counselling but some beliefs remain solidly embedded in cultural imperatives of the importance of childbearing as well as culturally determined and enforced gender roles.Interventions that aim to target discordant couples must embrace the complex and dynamic understandings of HIV diagnosis and treatment in context of fluid relationships, and changing beliefs about HIV risk and treatment.

  1. Dendritic cells exposed to MVA-based HIV-1 vaccine induce highly functional HIV-1-specific CD8(+ T cell responses in HIV-1-infected individuals.

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    Núria Climent

    Full Text Available Currently, MVA virus vectors carrying HIV-1 genes are being developed as HIV-1/AIDS prophylactic/therapeutic vaccines. Nevertheless, little is known about the impact of these vectors on human dendritic cells (DC and their capacity to present HIV-1 antigens to human HIV-specific T cells. This study aimed to characterize the interaction of MVA and MVA expressing the HIV-1 genes Env-Gag-Pol-Nef of clade B (referred to as MVA-B in human monocyte-derived dendritic cells (MDDC and the subsequent processes of HIV-1 antigen presentation and activation of memory HIV-1-specific T lymphocytes. For these purposes, we performed ex vivo assays with MDDC and autologous lymphocytes from asymptomatic HIV-infected patients. Infection of MDDC with MVA-B or MVA, at the optimal dose of 0.3 PFU/MDDC, induced by itself a moderate degree of maturation of MDDC, involving secretion of cytokines and chemokines (IL1-ra, IL-7, TNF-α, IL-6, IL-12, IL-15, IL-8, MCP-1, MIP-1α, MIP-1β, RANTES, IP-10, MIG, and IFN-α. MDDC infected with MVA or MVA-B and following a period of 48 h or 72 h of maturation were able to migrate toward CCL19 or CCL21 chemokine gradients. MVA-B infection induced apoptosis of the infected cells and the resulting apoptotic bodies were engulfed by the uninfected MDDC, which cross-presented HIV-1 antigens to autologous CD8(+ T lymphocytes. MVA-B-infected MDDC co-cultured with autologous T lymphocytes induced a highly functional HIV-specific CD8(+ T cell response including proliferation, secretion of IFN-γ, IL-2, TNF-α, MIP-1β, MIP-1α, RANTES and IL-6, and strong cytotoxic activity against autologous HIV-1-infected CD4(+ T lymphocytes. These results evidence the adjuvant role of the vector itself (MVA and support the clinical development of prophylactic and therapeutic anti-HIV vaccines based on MVA-B.

  2. Barriers and facilitators of HIV prevention with heterosexual Latino couples: beliefs of four stakeholder groups.

    Science.gov (United States)

    Pérez-Jiménez, David; Seal, David W; Serrano-García, Irma

    2009-01-01

    Although HIV prevention interventions for women are efficacious, long-term behavior change maintenance within power-imbalanced heterosexual relationships has been difficult. To explore the feasibility, content, and format of an HIV intervention for Latino couples, the authors conducted 13 focus groups with HIV/AIDS researchers, service providers, and heterosexual men and women in Puerto Rico, the Dominican Republic, and Mexico. Reasons that participants thought that men should be involved in prevention efforts included promotion of shared responsibility, creation of a safe environment for open conversation about sex, and increased sexual negotiation skills. Perceived barriers to men's involvement included cultural taboos, sexual conservatism associated with Catholicism and machismo, and power-imbalanced relationships. Participants stressed the need for recruitment of men within naturally occurring settings or by influential community leaders. Participants indicated that couples-level interventions would be successful if they used strong coed facilitators, included both unigender and mixed-gender discussion opportunities, and addressed personally meaningful topics. Implications of these findings are discussed.

  3. Barriers and Facilitators of HIV Prevention With Heterosexual Latino Couples: Beliefs of Four Stakeholder Groups

    Science.gov (United States)

    Pérez-Jiménez, David; Seal, David W.; Serrano-García, Irma

    2012-01-01

    Although HIV prevention interventions for women are efficacious, long-term behavior change maintenance within power-imbalanced heterosexual relationships has been difficult. To explore the feasibility, content, and format of an HIV intervention for Latino couples, the authors conducted 13 focus groups with HIV/AIDS researchers, service providers, and heterosexual men and women in Puerto Rico, the Dominican Republic, and Mexico. Reasons that participants thought that men should be involved in prevention efforts included promotion of shared responsibility, creation of a safe environment for open conversation about sex, and increased sexual negotiation skills. Perceived barriers to men’s involvement included cultural taboos, sexual conservatism associated with Catholicism and machismo, and power-imbalanced relationships. Participants stressed the need for recruitment of men within naturally occurring settings or by influential community leaders. Participants indicated that couples-level interventions would be successful if they used strong coed facilitators, included both unigender and mixed-gender discussion opportunities, and addressed personally meaningful topics. Implications of these findings are discussed. PMID:19209976

  4. Hyperthermia stimulates HIV-1 replication.

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    Ferdinand Roesch

    Full Text Available HIV-infected individuals may experience fever episodes. Fever is an elevation of the body temperature accompanied by inflammation. It is usually beneficial for the host through enhancement of immunological defenses. In cultures, transient non-physiological heat shock (42-45°C and Heat Shock Proteins (HSPs modulate HIV-1 replication, through poorly defined mechanisms. The effect of physiological hyperthermia (38-40°C on HIV-1 infection has not been extensively investigated. Here, we show that culturing primary CD4+ T lymphocytes and cell lines at a fever-like temperature (39.5°C increased the efficiency of HIV-1 replication by 2 to 7 fold. Hyperthermia did not facilitate viral entry nor reverse transcription, but increased Tat transactivation of the LTR viral promoter. Hyperthermia also boosted HIV-1 reactivation in a model of latently-infected cells. By imaging HIV-1 transcription, we further show that Hsp90 co-localized with actively transcribing provirus, and this phenomenon was enhanced at 39.5°C. The Hsp90 inhibitor 17-AAG abrogated the increase of HIV-1 replication in hyperthermic cells. Altogether, our results indicate that fever may directly stimulate HIV-1 replication, in a process involving Hsp90 and facilitation of Tat-mediated LTR activity.

  5. Nucleolar protein trafficking in response to HIV-1 Tat: rewiring the nucleolus.

    Science.gov (United States)

    Jarboui, Mohamed Ali; Bidoia, Carlo; Woods, Elena; Roe, Barbara; Wynne, Kieran; Elia, Giuliano; Hall, William W; Gautier, Virginie W

    2012-01-01

    The trans-activator Tat protein is a viral regulatory protein essential for HIV-1 replication. Tat trafficks to the nucleoplasm and the nucleolus. The nucleolus, a highly dynamic and structured membrane-less sub-nuclear compartment, is the site of rRNA and ribosome biogenesis and is involved in numerous cellular functions including transcriptional regulation, cell cycle control and viral infection. Importantly, transient nucleolar trafficking of both Tat and HIV-1 viral transcripts are critical in HIV-1 replication, however, the role(s) of the nucleolus in HIV-1 replication remains unclear. To better understand how the interaction of Tat with the nucleolar machinery contributes to HIV-1 pathogenesis, we investigated the quantitative changes in the composition of the nucleolar proteome of Jurkat T-cells stably expressing HIV-1 Tat fused to a TAP tag. Using an organellar proteomic approach based on mass spectrometry, coupled with Stable Isotope Labelling in Cell culture (SILAC), we quantified 520 proteins, including 49 proteins showing significant changes in abundance in Jurkat T-cell nucleolus upon Tat expression. Numerous proteins exhibiting a fold change were well characterised Tat interactors and/or known to be critical for HIV-1 replication. This suggests that the spatial control and subcellular compartimentaliation of these cellular cofactors by Tat provide an additional layer of control for regulating cellular machinery involved in HIV-1 pathogenesis. Pathway analysis and network reconstruction revealed that Tat expression specifically resulted in the nucleolar enrichment of proteins collectively participating in ribosomal biogenesis, protein homeostasis, metabolic pathways including glycolytic, pentose phosphate, nucleotides and amino acids biosynthetic pathways, stress response, T-cell signaling pathways and genome integrity. We present here the first differential profiling of the nucleolar proteome of T-cells expressing HIV-1 Tat. We discuss how these

  6. Methamphetamine inhibits HIV-1 replication in CD4+ T cells by modulating anti-HIV-1 miRNA expression.

    Science.gov (United States)

    Mantri, Chinmay K; Mantri, Jyoti V; Pandhare, Jui; Dash, Chandravanu

    2014-01-01

    Methamphetamine is the second most frequently used illicit drug in the United States. Methamphetamine abuse is associated with increased risk of HIV-1 acquisition, higher viral loads, and enhanced HIV-1 pathogenesis. Although a direct link between methamphetamine abuse and HIV-1 pathogenesis remains to be established in patients, methamphetamine has been shown to increase HIV-1 replication in macrophages, dendritic cells, and cells of HIV transgenic mice. Intriguingly, the effects of methamphetamine on HIV-1 replication in human CD4(+) T cells that serve as the primary targets of infection in vivo are not clearly understood. Therefore, we examined HIV-1 replication in primary CD4(+) T cells in the presence of methamphetamine in a dose-dependent manner. Our results demonstrate that methamphetamine had a minimal effect on HIV-1 replication at concentrations of 1 to 50 μmol/L. However, at concentrations >100 μmol/L, it inhibited HIV-1 replication in a dose-dependent manner. We also discovered that methamphetamine up-regulated the cellular anti-HIV-1 microRNAs (miR-125b, miR-150, and miR-28-5p) in CD4(+) T cells. Knockdown experiments illustrated that up-regulation of the anti-HIV miRNAs inhibited HIV-1 replication. These results are contrary to the paradigm that methamphetamine accentuates HIV-1 pathogenesis by increasing HIV-1 replication. Therefore, our findings underline the complex interaction between drug use and HIV-1 and necessitate comprehensive understanding of the effects of methamphetamine on HIV-1 pathogenesis. Copyright © 2014 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  7. HIV-1 genetic diversity and its distribution characteristics among newly diagnosed HIV-1 individuals in Hebei province, China.

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    Lu, Xinli; Zhao, Cuiying; Wang, Wei; Nie, Chenxi; Zhang, Yuqi; Zhao, Hongru; Chen, Suliang; Cui, Ze

    2016-01-01

    Since the first HIV-1 case in 1989, Hebei province has presented a clearly rising trend of HIV-1 prevalence, and HIV-1 genetic diversity has become the vital barrier to HIV prevention and control in this area. To obtain detailed information of HIV-1 spread in different populations and in different areas of Hebei, a cross-sectional HIV-1 molecular epidemiological investigation was performed across the province. Blood samples of 154 newly diagnosed HIV-1 individuals were collected from ten prefectures in Hebei using stratified sampling. Partial gag and env genes were amplified and sequenced. HIV-1 genotypes were identified by phylogenetic tree analyses. Among the 139 subjects genotyped, six HIV-1 subtypes were identified successfully, including subtype B (41.0 %), CRF01_AE (40.3 %), CRF07_BC (11.5 %), CRF08_BC (4.3 %), unique recombinant forms (URFs) (1.4 %) and subtype C (1.4 %). Subtype B was identified as the most frequent subtype. Two URF recombination patterns were the same as CRF01_AE/B. HIV-1 genotype distribution showed a significant statistical difference in different demographic characteristics, such as source (P  0.05). The differences in HIV-1 genotype distribution were closely associated with transmission routes. Particularly, all six subtype strains were found in heterosexuals, showing that HIV-1 has spread from the high-risk populations to the general populations in Hebei, China. In addition, CRF01_AE instead of subtype B has become the major strain of HIV-1 infection among homosexuals. Our study revealed HIV-1 evolution and genotype distribution by investigating newly diagnosed HIV-1 individuals in Hebei, China. This study provides important information to enhance the strategic plan for HIV prevention and control in China.

  8. Promotion of couples' voluntary HIV counseling and testing: a comparison of influence networks in Rwanda and Zambia.

    Science.gov (United States)

    Kelley, April L; Hagaman, Ashley K; Wall, Kristin M; Karita, Etienne; Kilembe, William; Bayingana, Roger; Tichacek, Amanda; Kautzman, Michele; Allen, Susan A

    2016-08-08

    Many African adults do not know that partners in steady or cohabiting relationships can have different HIV test results. Despite WHO recommendations for couples' voluntary counseling and testing (CVCT), fewer than 10 % of couples have been jointly tested and counseled. We examine the roles and interactions of influential network leaders (INLs) and influential network agents (INAs) in promoting CVCT in Kigali, Rwanda and Lusaka, Zambia. INLs were identified in the faith-based, non-governmental, private, and health sectors. Each INL recruited and mentored several INAs who promoted CVCT. INLs and INAs were interviewed about demographic characteristics, promotional efforts, and working relationships. We also surveyed CVCT clients about sources of CVCT information. In Zambia, 53 INAs and 31 INLs were surveyed. In Rwanda, 33 INAs and 27 INLs were surveyed. Most (75 %-90 %) INAs believed that INL support was necessary for their promotional work. Zambian INLs reported being more engaged with their INAs than Rwandan INLs, with 58 % of Zambian INLs reporting that they gave a lot of support to their INAs versus 39 % in Rwanda. INAs in both Rwanda and Zambia reported promoting CVCT via group forums (77 %-97 %) and speaking to a community leader about CVCT (79 %-88 %) in the past month. More Rwandan INAs and INLs reported previous joint or individual HIV testing compared with their Zambian counterparts, of which more than half had not been tested. In Zambia and Rwanda, 1271 and 3895 CVCT clients were surveyed, respectively. Hearing about CVCT from INAs during one-on-one promotions was the most frequent source of information reported by clients in Zambia (71 %). In contrast, Rwandan couples who tested were more likely to have heard about CVCT from a previously tested couple (59 %). CVCT has long been endorsed for HIV prevention but few couples have been reached. Influential social networks can successfully promote evidence-based HIV prevention in Africa. Support from

  9. Selective elimination of HIV-1-infected cells by Env-directed, HIV-1-based virus-like particles

    International Nuclear Information System (INIS)

    Peretti, Silvia; Schiavoni, Ilaria; Pugliese, Katherina; Federico, Maurizio

    2006-01-01

    We recently showed that both replicating and resting cells cultivated with ganciclovir (GCV) were killed when challenged with vesicular stomatitis virus G glycoprotein pseudotyped HIV-1-based virus-like particles (VLPs) carrying the Nef7 (i.e., an HIV-1 Nef mutant incorporating in virions at high levels)/herpes simplex virus-1 thymidine kinase (HSV-TK) fusion product. On this basis, a novel anti-HIV therapeutic approach based on Nef7/TK VLPs expressing X4 or R5 HIV cell receptor complexes has been attempted. We here report that (CD4-CXCR4) and (CD4-CCR5) Nef7-based VLPs efficiently enter cells infected by X4- or R5-tropic HIV-1 strains, respectively. Importantly, the delivery of the VLP-associated Nef7/TK led to cell death upon GCV treatment. Of interest, VLPs were effective also against non-replicating, HIV-1-infected primary human monocyte-derived macrophages. HIV-targeted VLPs represent a promising candidate for the treatment of persistently HIV-1-infected cells that are part of virus reservoirs resistant to HAART therapies

  10. Use of antiretroviral therapy in households and risk of HIV acquisition in rural KwaZulu-Natal, South Africa, 2004–12: a prospective cohort study

    Science.gov (United States)

    Vandormael, Alain; Newell, Marie-Louise; Bärnighausen, Till; Tanser, Frank

    2014-01-01

    Summary Background Studies of HIV-serodiscordant couples in stable sexual relationships have provided convincing evidence that antiretroviral therapy can prevent the transmission of HIV. We aimed to quantify the preventive effect of a public-sector HIV treatment and care programme based in a community with poor knowledge and disclosure of HIV status, frequent migration, late marriage, and multiple partnerships. Specifically, we assessed whether an individual's hazard of HIV acquisition was associated with antiretroviral therapy coverage among household members of the opposite sex. Methods In this prospective cohort study, we linked patients' records from a public-sector HIV treatment programme in rural KwaZulu-Natal, South Africa, with population-based HIV surveillance data collected between 2004 and 2012. We used information about coresidence to construct estimates of HIV prevalence and antiretroviral therapy coverage for each household. We then regressed the time to HIV seroconversion for 14 505 individuals, who were HIV-uninfected at baseline and individually followed up over time regarding their HIV status, on opposite-sex household antiretroviral therapy coverage, controlling for household HIV prevalence and a range of other potential confounders. Findings 2037 individual HIV seroconversions were recorded during 54 845 person-years of follow-up. For each increase of ten percentage points in opposite-sex household antiretroviral therapy coverage, the HIV acquisition hazard was reduced by 6% (95% CI 2–9), after controlling for other factors. This effect size translates into large reductions in HIV acquisition hazards when household antiretroviral therapy coverage is substantially increased. For example, an increase of 50 percentage points in household antiretroviral therapy coverage (eg, from 20% to 70%) reduced the hazard of HIV acquisition by 26% (95% CI 9–39). Interpretation Our findings provide further evidence that antiretroviral therapy

  11. HIV-1-Specific IgA Monoclonal Antibodies from an HIV-1 Vaccinee Mediate Galactosylceramide Blocking and Phagocytosis

    Science.gov (United States)

    2018-01-01

    ABSTRACT Vaccine-elicited humoral immune responses comprise an array of antibody forms and specificities, with only a fraction contributing to protective host immunity. Elucidation of antibody effector functions responsible for protective immunity against human immunodeficiency virus type 1 (HIV-1) acquisition is a major goal for the HIV-1 vaccine field. Immunoglobulin A (IgA) is an important part of the host defense against pathogens; however, little is known about the role of vaccine-elicited IgA and its capacity to mediate antiviral functions. To identify the antiviral functions of HIV-1-specific IgA elicited by vaccination, we cloned HIV-1 envelope-specific IgA monoclonal antibodies (MAbs) by memory B cell cultures from peripheral blood mononuclear cells from an RV144 vaccinee and produced two IgA clonal cell lines (HG129 and HG130) producing native, nonrecombinant IgA MAbs. The HG129 and HG130 MAbs mediated phagocytosis by monocytes, and HG129 blocked HIV-1 Env glycoprotein binding to galactosylceramide, an alternative HIV-1 receptor. These findings elucidate potential antiviral functions of vaccine-elicited HIV-1 envelope-specific IgA that may act to block HIV-1 acquisition at the portal of entry by preventing HIV-1 binding to galactosylceramide and mediating antibody Fc receptor-mediated virion phagocytosis. Furthermore, these findings highlight the complex and diverse interactions of vaccine-elicited IgA with pathogens that depend on IgA fine specificity and form (e.g., multimeric or monomeric) in the systemic circulation and mucosal compartments. IMPORTANCE Host-pathogen interactions in vivo involve numerous immune mechanisms that can lead to pathogen clearance. Understanding the nature of antiviral immune mechanisms can inform the design of efficacious HIV-1 vaccine strategies. Evidence suggests that both neutralizing and nonneutralizing antibodies can mediate some protection against HIV in animal models. Although numerous studies have characterized the

  12. Identifying HIV-1 dual infections

    Directory of Open Access Journals (Sweden)

    Cornelissen Marion

    2007-09-01

    Full Text Available Abstract Transmission of human immunodeficiency virus (HIV is no exception to the phenomenon that a second, productive infection with another strain of the same virus is feasible. Experiments with RNA viruses have suggested that both coinfections (simultaneous infection with two strains of a virus and superinfections (second infection after a specific immune response to the first infecting strain has developed can result in increased fitness of the viral population. Concerns about dual infections with HIV are increasing. First, the frequent detection of superinfections seems to indicate that it will be difficult to develop a prophylactic vaccine. Second, HIV-1 superinfections have been associated with accelerated disease progression, although this is not true for all persons. In fact, superinfections have even been detected in persons controlling their HIV infections without antiretroviral therapy. Third, dual infections can give rise to recombinant viruses, which are increasingly found in the HIV-1 epidemic. Recombinants could have increased fitness over the parental strains, as in vitro models suggest, and could exhibit increased pathogenicity. Multiple drug resistant (MDR strains could recombine to produce a pan-resistant, transmittable virus. We will describe in this review what is presently known about super- and re-infection among ambient viral infections, as well as the first cases of HIV-1 superinfection, including HIV-1 triple infections. The clinical implications, the impact of the immune system, and the effect of anti-retroviral therapy will be covered, as will as the timing of HIV superinfection. The methods used to detect HIV-1 dual infections will be discussed in detail. To increase the likelihood of detecting a dual HIV-1 infection, pre-selection of patients can be done by serotyping, heteroduplex mobility assays (HMA, counting the degenerate base codes in the HIV-1 genotyping sequence, or surveying unexpected increases in the

  13. Gendered power dynamics and women's negotiation of family planning in a high HIV prevalence setting: a qualitative study of couples in western Kenya.

    Science.gov (United States)

    Harrington, Elizabeth K; Dworkin, Shari; Withers, Mellissa; Onono, Maricianah; Kwena, Zachary; Newmann, Sara J

    2016-01-01

    In sub-Saharan Africa, high burdens of HIV and unmet need for contraception often coexist. Research emphasises the need to engage men and couples in reproductive health, yet couples' negotiations around fertility and family planning in the context of HIV have been sparsely studied. This study examined the gendered power dynamics that frame women's and couples' negotiations of contraceptive use in western Kenya. We conducted 76 in-depth interviews with 38 couples, of whom 22 couples were concordant HIV-positive. Qualitative data were analysed using a grounded theory approach. Direct communication around contraception with men was often challenging due to perceived or expressed male resistance. A substantial minority of women avoided male reproductive decision-making authority through covert contraceptive use, with concern for severe consequences when contraceptive use was discovered. Many men assumed that family planning use signified female promiscuity and that infidelity motivated covert use. Men were more willing to use condoms to avoid HIV re-infection or on the recommendation of HIV care providers, which allowed some women leverage to insist on condom use. Our findings highlight the tension between male dominated reproductive decision making and women's agency and point to the need for gender transformative approaches seeking to challenge masculinities that negatively impact health.

  14. HIV-1 Latency in Monocytes/Macrophages

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    Amit Kumar

    2014-04-01

    Full Text Available Human immunodeficiency virus type 1 (HIV-1 targets CD4+ T cells and cells of the monocyte/macrophage lineage. HIV pathogenesis is characterized by the depletion of T lymphocytes and by the presence of a population of cells in which latency has been established called the HIV-1 reservoir. Highly active antiretroviral therapy (HAART has significantly improved the life of HIV-1 infected patients. However, complete eradication of HIV-1 from infected individuals is not possible without targeting latent sources of infection. HIV-1 establishes latent infection in resting CD4+ T cells and findings indicate that latency can also be established in the cells of monocyte/macrophage lineage. Monocyte/macrophage lineage includes among others, monocytes, macrophages and brain resident macrophages. These cells are relatively more resistant to apoptosis induced by HIV-1, thus are important stable hideouts of the virus. Much effort has been made in the direction of eliminating HIV-1 resting CD4+ T-cell reservoirs. However, it is impossible to achieve a cure for HIV-1 without considering these neglected latent reservoirs, the cells of monocyte/macrophage lineage. In this review we will describe our current understanding of the mechanism of latency in monocyte/macrophage lineage and how such cells can be specifically eliminated from the infected host.

  15. Values and Preferences on the Use of Oral Pre-exposure Prophylaxis (PrEP) for HIV Prevention Among Multiple Populations: A Systematic Review of the Literature.

    Science.gov (United States)

    Koechlin, Florence M; Fonner, Virginia A; Dalglish, Sarah L; O'Reilly, Kevin R; Baggaley, Rachel; Grant, Robert M; Rodolph, Michelle; Hodges-Mameletzis, Ioannis; Kennedy, Caitlin E

    2017-05-01

    Daily oral pre-exposure prophylaxis (PrEP) is the use of antiretroviral drugs by HIV-negative people to prevent HIV infection. WHO released new guidelines in 2015 recommending PrEP for all populations at substantial risk of HIV infection. To prepare these guidelines, we conducted a systematic review of values and preferences among populations that might benefit from PrEP, women, heterosexual men, young women and adolescent girls, female sex workers, serodiscordant couples, transgender people and people who inject drugs, and among healthcare providers who may prescribe PrEP. A comprehensive search strategy reviewed three electronic databases of articles and HIV-related conference abstracts (January 1990-April 2015). Data abstraction used standardised forms to categorise by population groups and relevant themes. Of 3068 citations screened, 76 peer-reviewed articles and 28 conference abstracts were included. Geographic coverage was global. Most studies (N = 78) evaluated hypothetical use of PrEP, while 26 studies included individuals who actually took PrEP or placebo. Awareness of PrEP was low, but once participants were presented with information about PrEP, the majority said they would consider using it. Concerns about safety, side effects, cost and effectiveness were the most frequently cited barriers to use. There was little indication of risk compensation. Healthcare providers would consider prescribing PrEP, but need more information before doing so. Findings from a rapidly expanding evidence base suggest that the majority of populations most likely to benefit from PrEP feel positively towards it. These same populations would benefit from overcoming current implementation challenges with the shortest possible delay.

  16. Development of an epitope-based HIV-1 vaccine strategy from HIV-1 lipopeptide to dendritic-based vaccines.

    Science.gov (United States)

    Surenaud, Mathieu; Lacabaratz, Christine; Zurawski, Gérard; Lévy, Yves; Lelièvre, Jean-Daniel

    2017-10-01

    Development of a safe, effective and globally affordable Human Immunodeficiency Virus strain 1 (HIV-1) vaccine offers the best hope for future control of the HIV-1 pandemic. However, with the exception of the recent RV144 trial, which elicited a modest level of protection against infection, no vaccine candidate has shown efficacy in preventing HIV-1 infection or in controlling virus replication in humans. There is also a great need for a successful immunotherapeutic vaccine since combination antiretroviral therapy (cART) does not eliminate the reservoir of HIV-infected cells. But to date, no vaccine candidate has proven to significantly alter the natural history of an individual with HIV-1 infection. Areas covered: For over 25 years, the ANRS (France Recherche Nord&Sud Sida-HIV hépatites) has been committed to an original program combining basic science and clinical research developing an epitope-based vaccine strategy to induce a multiepitopic cellular response against HIV-1. This review describes the evolution of concepts, based on strategies using HIV-1 lipopeptides towards the use of dendritic cell (DC) manipulation. Expert commentary: Understanding the crucial role of DCs in immune responses allowed moving from the non-specific administration of HIV-1 sequences with lipopeptides to DC-based vaccines. These DC-targeting strategies should improve HIV-1 vaccine efficacy.

  17. HIV-1 phylogenetic analysis shows HIV-1 transits through the meninges to brain and peripheral tissues.

    Science.gov (United States)

    Lamers, Susanna L; Gray, Rebecca R; Salemi, Marco; Huysentruyt, Leanne C; McGrath, Michael S

    2011-01-01

    Brain infection by the human immunodeficiency virus type 1 (HIV-1) has been investigated in many reports with a variety of conclusions concerning the time of entry and degree of viral compartmentalization. To address these diverse findings, we sequenced HIV-1 gp120 clones from a wide range of brain, peripheral and meningeal tissues from five patients who died from several HIV-1 associated disease pathologies. High-resolution phylogenetic analysis confirmed previous studies that showed a significant degree of compartmentalization in brain and peripheral tissue subpopulations. Some intermixing between the HIV-1 subpopulations was evident, especially in patients that died from pathologies other than HIV-associated dementia. Interestingly, the major tissue harboring virus from both the brain and peripheral tissues was the meninges. These results show that (1) HIV-1 is clearly capable of migrating out of the brain, (2) the meninges are the most likely primary transport tissues, and (3) infected brain macrophages comprise an important HIV reservoir during highly active antiretroviral therapy. Copyright © 2010 Elsevier B.V. All rights reserved.

  18. An online randomized controlled trial evaluating HIV prevention digital media interventions for men who have sex with men.

    Directory of Open Access Journals (Sweden)

    Sabina Hirshfield

    Full Text Available As HIV infection continues unabated, there is a need for effective interventions targeting at-risk men who have sex with men (MSM. Engaging MSM online where they meet sexual partners is critical for HIV prevention efforts.A randomized controlled trial (RCT conducted online among U.S. MSM recruited from several gay sexual networking websites assessed the impact of 2 HIV prevention videos and an HIV prevention webpage compared to a control condition for the study outcomes HIV testing, serostatus disclosure, and unprotected anal intercourse (UAI at 60-day follow-up. Video conditions were pooled due to reduced power from low retention (53%, n = 1,631. No participant incentives were provided.Follow-up was completed by 1,631 (53% of 3,092 eligible men. In the 60 days after the intervention, men in the pooled video condition were significantly more likely than men in the control to report full serostatus disclosure ('asked and told' with their last sexual partner (OR 1.32, 95% CI 1.01-1.74. Comparing baseline to follow-up, HIV-negative men in the pooled video (OR 0.70, 95% CI 0.54-0.91 and webpage condition (OR 0.43, 95% CI 0.25-0.72 significantly reduced UAI at follow-up. HIV-positive men in the pooled video condition significantly reduced UAI (OR 0.38, 95% CI 0.20-0.67 and serodiscordant UAI (OR 0.53, 95% CI 0.28-0.96 at follow-up.Findings from this online RCT of MSM recruited from sexual networking websites suggest that a low cost, brief digital media intervention designed to engage critical thinking can increase HIV disclosure to sexual partners and decrease sexual risk. Effective, brief HIV prevention interventions featuring digital media that are made widely available may serve as a complementary part of an overall behavioral and biomedical strategy for reducing sexual risk by addressing the specific needs and circumstances of the target population, and by changing individual knowledge, motivations, and community norms.ClinicalTrials.gov NCT

  19. Modulation of chromatin structure by the FACT histone chaperone complex regulates HIV-1 integration.

    Science.gov (United States)

    Matysiak, Julien; Lesbats, Paul; Mauro, Eric; Lapaillerie, Delphine; Dupuy, Jean-William; Lopez, Angelica P; Benleulmi, Mohamed Salah; Calmels, Christina; Andreola, Marie-Line; Ruff, Marc; Llano, Manuel; Delelis, Olivier; Lavigne, Marc; Parissi, Vincent

    2017-07-28

    Insertion of retroviral genome DNA occurs in the chromatin of the host cell. This step is modulated by chromatin structure as nucleosomes compaction was shown to prevent HIV-1 integration and chromatin remodeling has been reported to affect integration efficiency. LEDGF/p75-mediated targeting of the integration complex toward RNA polymerase II (polII) transcribed regions ensures optimal access to dynamic regions that are suitable for integration. Consequently, we have investigated the involvement of polII-associated factors in the regulation of HIV-1 integration. Using a pull down approach coupled with mass spectrometry, we have selected the FACT (FAcilitates Chromatin Transcription) complex as a new potential cofactor of HIV-1 integration. FACT is a histone chaperone complex associated with the polII transcription machinery and recently shown to bind LEDGF/p75. We report here that a tripartite complex can be formed between HIV-1 integrase, LEDGF/p75 and FACT in vitro and in cells. Biochemical analyzes show that FACT-dependent nucleosome disassembly promotes HIV-1 integration into chromatinized templates, and generates highly favored nucleosomal structures in vitro. This effect was found to be amplified by LEDGF/p75. Promotion of this FACT-mediated chromatin remodeling in cells both increases chromatin accessibility and stimulates HIV-1 infectivity and integration. Altogether, our data indicate that FACT regulates HIV-1 integration by inducing local nucleosomes dissociation that modulates the functional association between the incoming intasome and the targeted nucleosome.

  20. Effect of HSV-2 infection on subsequent HIV acquisition: an updated systematic review and meta-analysis.

    Science.gov (United States)

    Looker, Katharine J; Elmes, Jocelyn A R; Gottlieb, Sami L; Schiffer, Joshua T; Vickerman, Peter; Turner, Katherine M E; Boily, Marie-Claude

    2017-12-01

    HIV and herpes simplex virus type 2 (HSV-2) infections cause a substantial global disease burden and are epidemiologically correlated. Two previous systematic reviews of the association between HSV-2 and HIV found evidence that HSV-2 infection increases the risk of HIV acquisition, but these reviews are now more than a decade old. For this systematic review and meta-analysis, we searched PubMed, MEDLINE, and Embase (from Jan 1, 2003, to May 25, 2017) to identify studies investigating the risk of HIV acquisition after exposure to HSV-2 infection, either at baseline (prevalent HSV-2 infection) or during follow-up (incident HSV-2 infection). Studies were included if they were a cohort study, controlled trial, or case-control study (including case-control studies nested within a cohort study or clinical trial); if they assessed the effect of pre-existing HSV-2 infection on HIV acquisition; and if they determined the HSV-2 infection status of study participants with a type-specific assay. We calculated pooled random-effect estimates of the association between prevalent or incident HSV-2 infection and HIV seroconversion. We also extended previous investigations through detailed meta-regression and subgroup analyses. In particular, we investigated the effect of sex and risk group (general population vs higher-risk populations) on the relative risk (RR) of HIV acquisition after prevalent or incident HSV-2 infection. Higher-risk populations included female sex workers and their clients, men who have sex with men, serodiscordant couples, and attendees of sexually transmitted infection clinics. We identified 57 longitudinal studies exploring the association between HSV-2 and HIV. HIV acquisition was almost tripled in the presence of prevalent HSV-2 infection among general populations (adjusted RR 2·7, 95% CI 2·2-3·4; number of estimates [N e ]=22) and was roughly doubled among higher-risk populations (1·7, 1·4-2·1; N e =25). Incident HSV-2 infection in general

  1. Nup153 and Nup98 bind the HIV-1 core and contribute to the early steps of HIV-1 replication

    Energy Technology Data Exchange (ETDEWEB)

    Di Nunzio, Francesca, E-mail: francesca.di-nunzio@pasteur.fr [Molecular Virology and Vaccinology unit, CNRS URA 3015, Department of Virology, Institut Pasteur, 25-28 rue du Dr. Roux, 75015 Paris (France); Fricke, Thomas [Department of Microbiology and Immunology, Albert Einstein College of Medicine Bronx, NY 10461 (United States); Miccio, Annarita [University of Modena e Reggio Emilia, Centro di Medicina Rigenerativa, Modena (Italy); Valle-Casuso, Jose Carlos; Perez, Patricio [Department of Microbiology and Immunology, Albert Einstein College of Medicine Bronx, NY 10461 (United States); Souque, Philippe [Molecular Virology and Vaccinology unit, CNRS URA 3015, Department of Virology, Institut Pasteur, 25-28 rue du Dr. Roux, 75015 Paris (France); Rizzi, Ermanno; Severgnini, Marco [Institute of Biomedical Technologies, CNR, Milano (Italy); Mavilio, Fulvio [University of Modena e Reggio Emilia, Centro di Medicina Rigenerativa, Modena (Italy); Genethon, Evry (France); Charneau, Pierre [Molecular Virology and Vaccinology unit, CNRS URA 3015, Department of Virology, Institut Pasteur, 25-28 rue du Dr. Roux, 75015 Paris (France); Diaz-Griffero, Felipe, E-mail: felipe.diaz-griffero@einstein.yu.edu [Department of Microbiology and Immunology, Albert Einstein College of Medicine Bronx, NY 10461 (United States)

    2013-05-25

    The early steps of HIV-1 replication involve the entry of HIV-1 into the nucleus, which is characterized by viral interactions with nuclear pore components. HIV-1 developed an evolutionary strategy to usurp the nuclear pore machinery and chromatin in order to integrate and efficiently express viral genes. In the current work, we studied the role of nucleoporins 153 and 98 (Nup153 and Nup98) in infection of human Jurkat lymphocytes by HIV-1. We showed that Nup153-depleted cells exhibited a defect in nuclear import, while depletion of Nup 98 caused a slight defect in HIV integration. To explore the biochemical viral determinants for the requirement of Nup153 and Nup98 during HIV-1 infection, we tested the ability of these nucleoporins to interact with HIV-1 cores. Our findings showed that both nucleoporins bind HIV-1 cores suggesting that this interaction is important for HIV-1 nuclear import and/or integration. Distribution analysis of integration sites in Nup153-depleted cells revealed a reduced tendency of HIV-1 to integrate in intragenic sites, which in part could account for the large infectivity defect observed in Nup153-depleted cells. Our work strongly supports a role for Nup153 in HIV-1 nuclear import and integration. - Highlights: ► We studied the role of Nup98 and Nup153 in HIV-1 infection. ► Nup98 binds the HIV-1 core and is involved in HIV-1 integration. ► Nup153 binds the HIV-1 core and is involved in HIV-1 nuclear import. ► Depletion of Nup153 decreased the integration of HIV-1 in transcriptionally active sites.

  2. Nup153 and Nup98 bind the HIV-1 core and contribute to the early steps of HIV-1 replication

    International Nuclear Information System (INIS)

    Di Nunzio, Francesca; Fricke, Thomas; Miccio, Annarita; Valle-Casuso, Jose Carlos; Perez, Patricio; Souque, Philippe; Rizzi, Ermanno; Severgnini, Marco; Mavilio, Fulvio; Charneau, Pierre; Diaz-Griffero, Felipe

    2013-01-01

    The early steps of HIV-1 replication involve the entry of HIV-1 into the nucleus, which is characterized by viral interactions with nuclear pore components. HIV-1 developed an evolutionary strategy to usurp the nuclear pore machinery and chromatin in order to integrate and efficiently express viral genes. In the current work, we studied the role of nucleoporins 153 and 98 (Nup153 and Nup98) in infection of human Jurkat lymphocytes by HIV-1. We showed that Nup153-depleted cells exhibited a defect in nuclear import, while depletion of Nup 98 caused a slight defect in HIV integration. To explore the biochemical viral determinants for the requirement of Nup153 and Nup98 during HIV-1 infection, we tested the ability of these nucleoporins to interact with HIV-1 cores. Our findings showed that both nucleoporins bind HIV-1 cores suggesting that this interaction is important for HIV-1 nuclear import and/or integration. Distribution analysis of integration sites in Nup153-depleted cells revealed a reduced tendency of HIV-1 to integrate in intragenic sites, which in part could account for the large infectivity defect observed in Nup153-depleted cells. Our work strongly supports a role for Nup153 in HIV-1 nuclear import and integration. - Highlights: ► We studied the role of Nup98 and Nup153 in HIV-1 infection. ► Nup98 binds the HIV-1 core and is involved in HIV-1 integration. ► Nup153 binds the HIV-1 core and is involved in HIV-1 nuclear import. ► Depletion of Nup153 decreased the integration of HIV-1 in transcriptionally active sites

  3. Anti-HIV-1 activity of flavonoid myricetin on HIV-1 infection in a dual-chamber in vitro model.

    Directory of Open Access Journals (Sweden)

    Silvana Pasetto

    Full Text Available HIV infection by sexual transmission remains an enormous global health concern. More than 1 million new infections among women occur annually. Microbicides represent a promising prevention strategy that women can easily control. Among emerging therapies, natural small molecules such as flavonoids are an important source of new active substances. In this study we report the in vitro cytotoxicity and anti-HIV-1 and microbicide activity of the following flavonoids: Myricetin, Quercetin and Pinocembrin. Cytotoxicity tests were conducted on TZM-bl, HeLa, PBMC, and H9 cell cultures using 0.01-100 µM concentrations. Myricetin presented the lowest toxic effect, with Quercetin and Pinocembrin relatively more toxic. The anti-HIV-1 activity was tested with TZM-bl cell plus HIV-1 BaL (R5 tropic, H9 and PBMC cells plus HIV-1 MN (X4 tropic, and the dual tropic (X4R5 HIV-1 89.6. All flavonoids showed anti-HIV activity, although Myricetin was more effective than Quercetin or Pinocembrin. In TZM-bl cells, Myricetin inhibited ≥90% of HIV-1 BaL infection. The results were confirmed by quantification of HIV-1 p24 antigen in supernatant from H9 and PBMC cells following flavonoid treatment. In H9 and PBMC cells infected by HIV-1 MN and HIV-1 89.6, Myricetin showed more than 80% anti-HIV activity. Quercetin and Pinocembrin presented modest anti-HIV activity in all experiments. Myricetin activity was tested against HIV-RT and inhibited the enzyme by 49%. Microbicide activities were evaluated using a dual-chamber female genital tract model. In the in vitro microbicide activity model, Myricetin showed promising results against different strains of HIV-1 while also showing insignificant cytotoxic effects. Further studies of Myricetin should be performed to identify its molecular targets in order to provide a solid biological foundation for translational research.

  4. Spousal communication about HIV prevention in Kenya.

    Science.gov (United States)

    Chiao, Chi; Mishra, Vinod; Ksobiech, Kate

    2011-11-01

    High HIV rates among cohabiting couples in many African countries have led to greater programmatic emphasis on spousal communication in HIV prevention. This study examines how demographic and socioeconomic characteristics of cohabiting adults influence their dyadic communication about HIV. A central focus of this research is on how the position of women relative to their male partners influences spousal communication about HIV prevention. The authors analyze gaps in spousal age and education and females' participation in household decision making as key factors influencing spousal communication about HIV, while controlling for sexual behaviors of both partners as well as other individual and contextual factors. Data were obtained from the 2003 Kenya Demographic and Health Survey for 1,388 cohabiting couples. Information regarding spousal communication was self-reported, assessing whether both, either, or neither partner ever discussed HIV prevention with the other. Analyses showed higher levels of education for the female partner and participation in household decision making are positively associated with spousal communication about HIV prevention. With females' education and other factors controlled, couples with more educated male partners were more likely to have discussed HIV prevention than couples in which both partners have the same level of education. Spousal communication was also positively associated with household wealth status and exposure to the mass media, but couples in which male partners reported having nonspousal sex in the past year were less likely to have discussed HIV prevention with their spouses. Findings suggest HIV prevention programs should promote female empowerment and encourage male participation in sexual health discussion.

  5. Long-term nonprogression and broad HIV-1-specific proliferative T-cell responses

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    Nesrina eImami

    2013-03-01

    Full Text Available Complex mechanisms underlying the maintenance of fully functional, proliferative, HIV-1-specific T-cell responses involve processes from early T-cell development through to the final stages of T-cell differentiation and antigen recognition. Virus-specific proliferative CD4 and CD8 T-cell responses, important for the control of infection, are observed in some HIV-1+ patients during early stages of disease, and are maintained in long-term nonprogressing subjects. In the vast majority of HIV-1+ patients, full immune functionality is lost when proliferative HIV-1-specific T-cell responses undergo a variable progressive decline throughout the course of chronic infection. This appears irreparable despite administration of potent combination antiretroviral therapy, which to date is non-curative, necessitating life-long administration and the development of effective, novel, therapeutic interventions. While a sterilising cure, involving clearance of virus from the host, remains a primary aim, a functional cure may be a more feasible goal with considerable impact on worldwide HIV-1 infection. Such an approach would enable long-term co-existence of host and virus in the absence of toxic and costly drugs. Effective immune homeostasis coupled with a balanced response appropriately targeting conserved viral antigens, in a manner that avoids hyperactivation and exhaustion, may prove to be the strongest correlate of durable viral control. This review describes novel concepts underlying full immune functionality in the context of HIV-1 infection, which may be utilised in future strategies designed to improve upon existing therapy. The aim will be to induce long-term nonprogressor or elite controller status in every infected host, through immune-mediated control of viraemia and reduction of viral reservoirs, leading to lower HIV-1 transmission rates.

  6. Cytoplasmic Dynein Promotes HIV-1 Uncoating

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    Paulina Pawlica

    2014-11-01

    Full Text Available Retroviral capsid (CA cores undergo uncoating during their retrograde transport (toward the nucleus, and/or after reaching the nuclear membrane. However, whether HIV-1 CA core uncoating is dependent upon its transport is not understood. There is some evidence that HIV-1 cores retrograde transport involves cytoplasmic dynein complexes translocating on microtubules. Here we investigate the role of dynein-dependent transport in HIV-1 uncoating. To interfere with dynein function, we depleted dynein heavy chain (DHC using RNA interference, and we over-expressed p50/dynamitin. In immunofluorescence microscopy experiments, DHC depletion caused an accumulation of CA foci in HIV-1 infected cells. Using a biochemical assay to monitor HIV-1 CA core disassembly in infected cells, we observed an increase in amounts of intact (pelletable CA cores upon DHC depletion or p50 over-expression. Results from these two complementary assays suggest that inhibiting dynein-mediated transport interferes with HIV-1 uncoating in infected cells, indicating the existence of a functional link between HIV-1 transport and uncoating.

  7. Recognition of HIV-1 peptides by host CTL is related to HIV-1 similarity to human proteins.

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    Morgane Rolland

    Full Text Available BACKGROUND: While human immunodeficiency virus type 1 (HIV-1-specific cytotoxic T lymphocytes preferentially target specific regions of the viral proteome, HIV-1 features that contribute to immune recognition are not well understood. One hypothesis is that similarities between HIV and human proteins influence the host immune response, i.e., resemblance between viral and host peptides could preclude reactivity against certain HIV epitopes. METHODOLOGY/PRINCIPAL FINDINGS: We analyzed the extent of similarity between HIV-1 and the human proteome. Proteins from the HIV-1 B consensus sequence from 2001 were dissected into overlapping k-mers, which were then probed against a non-redundant database of the human proteome in order to identify segments of high similarity. We tested the relationship between HIV-1 similarity to host encoded peptides and immune recognition in HIV-infected individuals, and found that HIV immunogenicity could be partially modulated by the sequence similarity to the host proteome. ELISpot responses to peptides spanning the entire viral proteome evaluated in 314 individuals showed a trend indicating an inverse relationship between the similarity to the host proteome and the frequency of recognition. In addition, analysis of responses by a group of 30 HIV-infected individuals against 944 overlapping peptides representing a broad range of individual HIV-1B Nef variants, affirmed that the degree of similarity to the host was significantly lower for peptides with reactive epitopes than for those that were not recognized. CONCLUSIONS/SIGNIFICANCE: Our results suggest that antigenic motifs that are scarcely represented in human proteins might represent more immunogenic CTL targets not selected against in the host. This observation could provide guidance in the design of more effective HIV immunogens, as sequences devoid of host-like features might afford superior immune reactivity.

  8. No evidence of association between HIV-1 and malaria in populations with low HIV-1 prevalence.

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    Diego F Cuadros

    Full Text Available The geographic overlap between HIV-1 and malaria has generated much interest in their potential interactions. A variety of studies have evidenced a complex HIV-malaria interaction within individuals and populations that may have dramatic effects, but the causes and implications of this co-infection at the population level are still unclear. In a previous publication, we showed that the prevalence of malaria caused by the parasite Plasmodium falciparum is associated with HIV infection in eastern sub-Saharan Africa. To complement our knowledge of the HIV-malaria co-infection, the objective of this work was to assess the relationship between malaria and HIV prevalence in the western region of sub-Saharan Africa.Population-based cross-sectional data were obtained from the HIV/AIDS Demographic and Health Surveys conducted in Burkina Faso, Ghana, Guinea, Mali, Liberia and Cameroon, and the malaria atlas project. Using generalized linear mixed models, we assessed the relationship between HIV-1 and Plasmodium falciparum parasite rate (PfPR adjusting for important socio-economic and biological cofactors. We found no evidence that individuals living in areas with stable malaria transmission (PfPR>0.46 have higher odds of being HIV-positive than individuals who live in areas with PfPR≤0.46 in western sub-Saharan Africa (estimated odds ratio 1.14, 95% confidence interval 0.86-1.50. In contrast, the results suggested that PfPR was associated with being infected with HIV in Cameroon (estimated odds ratio 1.56, 95% confidence interval 1.23-2.00.Contrary to our previous research on eastern sub-Saharan Africa, this study did not identify an association between PfPR and infection with HIV in western sub-Saharan Africa, which suggests that malaria might not play an important role in the spread of HIV in populations where the HIV prevalence is low. Our work highlights the importance of understanding the epidemiologic effect of co-infection and the relevant

  9. The role of NK cells in HIV-1 protection: autologous, allogeneic or both?

    Science.gov (United States)

    Hens, Jef; Jennes, Wim; Kestens, Luc

    2016-01-01

    transmission. Therefore, theoretically, HIV-1 would be eliminated before it has the chance to infect the autologous cells in the recipient. While this "alloreactive" NK cell mechanism is especially relevant to HIV transmission in monogamous couples, it would be interesting to investigate how it could influence resistance to HIV in other settings. The objective of this review is to summarize the knowledge about these autologous and alloreactive NK cell responses with regard to HIV-1 outcome.

  10. Human CNS cultures exposed to HIV-1 gp120 reproduce dendritic injuries of HIV-1-associated dementia

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    Hammond Robert R

    2004-05-01

    Full Text Available Abstract HIV-1-associated dementia remains a common subacute to chronic central nervous system degeneration in adult and pediatric HIV-1 infected populations. A number of viral and host factors have been implicated including the HIV-1 120 kDa envelope glycoprotein (gp120. In human post-mortem studies using confocal scanning laser microscopy for microtubule-associated protein 2 and synaptophysin, neuronal dendritic pathology correlated with dementia. In the present study, primary human CNS cultures exposed to HIV-1 gp120 at 4 weeks in vitro suffered gliosis and dendritic damage analogous to that described in association with HIV-1-associated dementia.

  11. Human endogenous retrovirus K Gag coassembles with HIV-1 Gag and reduces the release efficiency and infectivity of HIV-1.

    Science.gov (United States)

    Monde, Kazuaki; Contreras-Galindo, Rafael; Kaplan, Mark H; Markovitz, David M; Ono, Akira

    2012-10-01

    Human endogenous retroviruses (HERVs), which are remnants of ancestral retroviruses integrated into the human genome, are defective in viral replication. Because activation of HERV-K and coexpression of this virus with HIV-1 have been observed during HIV-1 infection, it is conceivable that HERV-K could affect HIV-1 replication, either by competition or by cooperation, in cells expressing both viruses. In this study, we found that the release efficiency of HIV-1 Gag was 3-fold reduced upon overexpression of HERV-K(CON) Gag. In addition, we observed that in cells expressing Gag proteins of both viruses, HERV-K(CON) Gag colocalized with HIV-1 Gag at the plasma membrane. Furthermore, HERV-K(CON) Gag was found to coassemble with HIV-1 Gag, as demonstrated by (i) processing of HERV-K(CON) Gag by HIV-1 protease in virions, (ii) coimmunoprecipitation of virion-associated HERV-K(CON) Gag with HIV-1 Gag, and (iii) rescue of a late-domain-defective HERV-K(CON) Gag by wild-type (WT) HIV-1 Gag. Myristylation-deficient HERV-K(CON) Gag localized to nuclei, suggesting cryptic nuclear trafficking of HERV-K Gag. Notably, unlike WT HERV-K(CON) Gag, HIV-1 Gag failed to rescue myristylation-deficient HERV-K(CON) Gag to the plasma membrane. Efficient colocalization and coassembly of HIV-1 Gag and HERV-K Gag also required nucleocapsid (NC). These results provide evidence that HIV-1 Gag heteromultimerizes with HERV-K Gag at the plasma membrane, presumably through NC-RNA interaction. Intriguingly, HERV-K Gag overexpression reduced not only HIV-1 release efficiency but also HIV-1 infectivity in a myristylation- and NC-dependent manner. Altogether, these results indicate that Gag proteins of endogenous retroviruses can coassemble with HIV-1 Gag and modulate the late phase of HIV-1 replication.

  12. The anti-HIV-1 effect of scutellarin

    International Nuclear Information System (INIS)

    Zhang Gaohong; Wang Qian; Chen Jijun; Zhang Xuemei; Tam, S.-C.; Zheng Yongtang

    2005-01-01

    Scutellarin was purified from the plant Erigeron breviscapus (Vant.) Hand.-Mazz. The activity against 3 strains of human immunodeficiency virus (HIV) was determined in vitro in this study. These were laboratory-derived virus (HIV-1 IIIB ), drug-resistant virus (HIV-1 74V ), and low-passage clinical isolated virus (HIV-1 KM018 ). From syncytia inhibition study, the EC 50 of scutellarin against HIV-1 IIIB direct infection in C8166 cells was 26 μM with a therapeutic index of 36. When the mode of infection changed from acute infection to cell-to-cell infection, this compound became even more potent and the EC 50 reduced to 15 μM. This suggested that cell fusion might be affected by this compound. By comparing the inhibitory effects on p24 antigen, scutellarin was also found to be active against HIV-1 74V (EC 50 253 μM) and HIV-1 KM018 (EC 50 136 μM) infection with significant difference in potency. The mechanism of its action was also explored in this study. At a concentration of 433 μM, scutellarin inhibited 48% of the cell free recombinant HIV-1 RT activity. It also caused 82% inhibition of HIV-1 particle attachment and 45% inhibition of fusion at the concentrations of 54 μM. In summary, scutellarin was found to inhibit several strains of HIV-1 replication with different potencies. It appeared to inhibit HIV-1 RT activity, HIV-1 particle attachment and cell fusion. These are essential activities for viral transmission and replication

  13. Access to fertility services in Canada for HIV-positive individuals and couples: a comparison between 2007 and 2014.

    Science.gov (United States)

    Lo, Carson K; Kennedy, V Logan; Yudin, Mark H; Shapiro, Heather M; Loutfy, Mona

    2017-11-01

    In the modern era of HIV care, a multitude of clinical needs have emerged; one such need is the growing sub-specialty of HIV and reproductive health. In 2007, a study surveying Canadian fertility clinics found limited access to fertility services for HIV-positive patients. Given the extensive efforts made to address this lack of services, a follow-up assessment was warranted. This study aimed to compare the access to Canadian fertility clinics and services for HIV-positive individuals and couples in 2014 and 2007. Surveys were sent to medical or laboratory directors of assisted reproductive technology (ART) clinics in 2014 and results were compared to those sent in 2007. Main outcome measures included: the proportion of fertility clinics willing to provide ART to people with HIV, the specific services offered, and whether the 2012 Canadian HIV Pregnancy Planning Guidelines were implemented to inform practice. Across Canadian provinces, 20/34 (59%) clinics completed the survey. Ninety-five percent (19/20) of clinics accepted HIV-positive patients for consultation. Only 50% (10/20) of clinics in four provinces offered a full range of ART (defined as including in vitro fertilization [IVF]). Ten clinics (50%) in five provinces were aware that guidelines exist; half (n = 5) having read them and four reporting implementation of all the guidelines' recommendations in their practice. Compared to 2007, more clinics had implemented separate facilities (p = 0.028) to treat HIV-positive individuals, offered IVF (p = 0.013) for HIV-positive female partners, sperm washing (p = 0.033) for HIV-positive male partners, and risk reduction techniques to couples with HIV-positive men and women (p = 0.006). Access to fertility clinics for people with HIV has improved over time but is still regionally dependent and access to full ART remains limited. These findings suggest the need for advocacy targeted towards geographical-specific areas and optimizing access to

  14. The Oncolytic Virus MG1 Targets and Eliminates Cells Latently Infected With HIV-1: Implications for an HIV Cure.

    Science.gov (United States)

    Ranganath, Nischal; Sandstrom, Teslin S; Burke Schinkel, Stephanie C; Côté, Sandra C; Angel, Jonathan B

    2018-02-14

    Cells latently infected with human immunodeficiency virus (HIV) evade immune- and drug-mediated clearance. These cells harbor intracellular signaling defects, including impairment of the antiviral type I interferon response. Such defects have also been observed in several cancers and have been exploited for the development of therapeutic oncolytic viruses, including the recombinant Maraba virus (MG1). We therefore hypothesized that MG1 would infect and eliminate cells latently infected with HIV-1, while sparing healthy uninfected cells. Preferential infection and elimination by MG1 was first demonstrated in cell lines latently infected with HIV-1. Following this, a reduction in HIV-1 DNA and inducible HIV-1 replication was observed following MG1 infection of latently infected, resting CD4+ T cells generated using an in vitro model of latency. Last, MG1 infection resulted in a reduction in HIV-1 DNA and inducible HIV-1 replication in memory CD4+ T cells isolated from effectively treated, HIV-1-infected individuals. Our results therefore highlight a novel approach to eliminate the latent HIV-1 reservoir. © The Author(s) 2017. Published by Oxford University Press for the Infectious Diseases Society of America.

  15. HIV prevalence, attitudes and behaviour in clients of a confidential HIV testing and counselling centre in Uganda.

    Science.gov (United States)

    Müller, O; Barugahare, L; Schwartländer, B; Byaruhanga, E; Kataaha, P; Kyeyune, D; Heckmann, W; Ankrah, M

    1992-08-01

    To describe clients, operation and impact of an African public HIV testing and counselling centre. Analysis of samples from clients attending the AIDS Information Centre (AIC) in Kampala, Uganda in early 1991. HIV-1-positive and HIV-negative consecutive clients (250 of each), 86 consecutive couples, and 200 consecutive clients who were HIV-negative in 1990 and were attending for their repeat test. HIV seroprevalence rates, attitudes, behaviour and behaviour change. HIV-1 prevalence was 28% overall, 24% in men and 35% in women. Reasons for taking the HIV test were a planned marriage or a new relationship (27%; 84% in couples), to plan for the future (35%), distrust of sexual partner (14%) and illness or disease/death (not HIV-specific) of partner (20%). The majority of the reported intentions in response to a positive or a negative HIV test result were positive, demonstrating the ability to cope with this information. Of repeat clients, two (1%) had become HIV-1-positive. The majority of repeat clients reported one sexual partner only (67%) or sexual abstinence (25%). Compared with pre-test information from AIC clients attending for the first time, repeat clients reported casual sexual contacts less often (6 versus 25%) and, of those, the majority used condoms. Our study demonstrates the demand for and the feasibility of confidential HIV testing and counseling services in Uganda, and illustrates the value of these services in achieving behaviour changes. Such services should be considered an additional approach for the reduction of HIV transmission in Africa, especially in areas with high HIV seroprevalence rates.

  16. Relationship power, communication, and violence among couples: results of a cluster-randomized HIV prevention study in a South African township

    Directory of Open Access Journals (Sweden)

    Minnis AM

    2015-05-01

    Full Text Available Alexandra M Minnis,1,2 Irene A Doherty,1,3 Tracy L Kline,1 William A Zule,1 Bronwyn Myers,4,5 Tara Carney,4 Wendee M Wechsberg1,3,6,7 1RTI International, Research Triangle Park, NC, 2School of Public Health, University of California, Berkeley, CA, 3University of North Carolina, Chapel Hill, NC, USA; 4Alcohol, Tobacco and Other Drug Research Unit, South African Medical Research Council, 5Department of Psychiatry and Mental Health, University of Cape Town, Cape Town, South Africa; 6North Carolina State University, Raleigh, 7Duke University School of Medicine, Durham, NC, USA Background: Inequitable gender-based power in relationships and intimate partner violence contribute to persistently high rates of HIV infection among South African women. We examined the effects of two group-based HIV prevention interventions that engaged men and their female partners together in a couples intervention (Couples Health CoOp [CHC] and a gender-separate intervention (Men’s Health CoOp/Women’s Health CoOp [MHC/WHC] on women’s reports of power, communication, and conflict in relationships. Methods: The cluster-randomized field experiment included heterosexual couples from a high-density South African township in which neighborhoods were randomized to one of the intervention arms or a control arm that received the WHC only. Participants completed in-person study visits at baseline and 6-month follow-up. We examined group differences using one-way analysis of variance and multivariable regression models.Results: Of the 290 couples enrolled, 255 women remained in the same partnership over 6 months. Following the intervention, women in the CHC arm compared with those in the WHC arm were more likely to report an increase in relationship control (ß=0.92, 95% confidence interval [CI]: 0.02, 1.83, P=0.045 and gender norms supporting female autonomy in relationships (ß=0.99, 95% CI: 0.07, 1.91, P=0.035. Women in the MHC/WHC arm were more likely to report increases

  17. Safety and immunogenicity of HIV-1 Tat toxoid in immunocompromised HIV-1-infected patients.

    Science.gov (United States)

    Gringeri, A; Santagostino, E; Muça-Perja, M; Mannucci, P M; Zagury, J F; Bizzini, B; Lachgar, A; Carcagno, M; Rappaport, J; Criscuolo, M; Blattner, W; Burny, A; Gallo, R C; Zagury, D

    1998-01-01

    To antagonize the deleterious effects of the HIV-1 toxin extracellular Tat on uninfected immune cells, we developed a new strategy of anti-HIV-1 vaccine using an inactivated but immunogenic Tat (Tat toxoid). Tat toxoid has been assayed for safety and immunogenicity in seropositive patients. The phase I vaccine clinical trial testing Tat toxoid preparation in Seppic Isa 51 oil adjuvant was performed on 14 HIV-1-infected asymptomatic although biologically immunocompromised individuals (500-200 CD4+ cells/mm3). Following as many as 8 injections, no clinical defects were observed. All patients exhibited an antibody (Ab) response to Tat, and some had cell-mediated immunity (CMI) as evaluated by skin test in vivo and T-cell proliferation in vitro. These results provide initial evidence of safety and potency of Tat toxoid vaccination in HIV-1-infected individuals.

  18. In vitro nuclear interactome of the HIV-1 Tat protein.

    LENUS (Irish Health Repository)

    Gautier, Virginie W

    2009-01-01

    BACKGROUND: One facet of the complexity underlying the biology of HIV-1 resides not only in its limited number of viral proteins, but in the extensive repertoire of cellular proteins they interact with and their higher-order assembly. HIV-1 encodes the regulatory protein Tat (86-101aa), which is essential for HIV-1 replication and primarily orchestrates HIV-1 provirus transcriptional regulation. Previous studies have demonstrated that Tat function is highly dependent on specific interactions with a range of cellular proteins. However they can only partially account for the intricate molecular mechanisms underlying the dynamics of proviral gene expression. To obtain a comprehensive nuclear interaction map of Tat in T-cells, we have designed a proteomic strategy based on affinity chromatography coupled with mass spectrometry. RESULTS: Our approach resulted in the identification of a total of 183 candidates as Tat nuclear partners, 90% of which have not been previously characterised. Subsequently we applied in silico analysis, to validate and characterise our dataset which revealed that the Tat nuclear interactome exhibits unique signature(s). First, motif composition analysis highlighted that our dataset is enriched for domains mediating protein, RNA and DNA interactions, and helicase and ATPase activities. Secondly, functional classification and network reconstruction clearly depicted Tat as a polyvalent protein adaptor and positioned Tat at the nexus of a densely interconnected interaction network involved in a range of biological processes which included gene expression regulation, RNA biogenesis, chromatin structure, chromosome organisation, DNA replication and nuclear architecture. CONCLUSION: We have completed the in vitro Tat nuclear interactome and have highlighted its modular network properties and particularly those involved in the coordination of gene expression by Tat. Ultimately, the highly specialised set of molecular interactions identified will

  19. Outcomes and lessons from a pilot RCT of a community-based HIV prevention multi-session group intervention for gay men.

    Science.gov (United States)

    Harding, R; Bensley, J; Corrigan, N; Franks, L; Stratman, J; Waller, Z; Warner, J

    2004-07-01

    This paper presents the first outcome evaluation of multi-session groupwork for HIV prevention among gay men in the UK. This community-based RCT recruited 50 men, of whom 42% were HIV-positive or untested, and 32% reported status unknown or serodiscordant UAI in the previous 12 months. No knowledge, skills, attitudinal or behavioural differences were detected between intervention and control at baseline. At eight weeks, those attending the group reported significant gains over their control in making sexual choices, physical safety, HIV and STI transmission knowledge, and sexual negotiation skills. At 20 weeks, significant differences remained for HIV and STI transmission knowledge and comfort with sexual choices. Although no behavioural differences were detected, the aims of the National Prevention Strategy were met. This pilot RCT is appraised in the light of modest sample size and attrition, and recommendations for establishing behavioural outcomes are presented. This study has demonstrated that high-risk community samples can be recruited to multi-session interventions, and has provided feasibility data for future rigorous evaluation designs.

  20. Inhibition of human immunodeficiency virus type 1 (HIV-1) nuclear import via Vpr-Importin α interactions as a novel HIV-1 therapy

    International Nuclear Information System (INIS)

    Suzuki, Tatsunori; Yamamoto, Norio; Nonaka, Mizuho; Hashimoto, Yoshie; Matsuda, Go; Takeshima, Shin-nosuke; Matsuyama, Megumi; Igarashi, Tatsuhiko; Miura, Tomoyuki; Tanaka, Rie; Kato, Shingo; Aida, Yoko

    2009-01-01

    The development of multidrug-resistant viruses compromises the efficacy of anti-human immunodeficiency virus (HIV) therapy and limits treatment options. Therefore, new targets that can be used to develop novel antiviral agents need to be identified. One such target is the interaction between Vpr, one of the accessory gene products of HIV-1 and Importin α, which is crucial, not only for the nuclear import of Vpr, but also for HIV-1 replication in macrophages. We have identified a potential parent compound, hematoxylin, which suppresses Vpr-Importin α interaction, thereby inhibiting HIV-1 replication in a Vpr-dependent manner. Analysis by real-time PCR demonstrated that hematoxylin specifically inhibited nuclear import step of pre-integration complex. Thus, hematoxylin is a new anti-HIV-1 inhibitor that targets the nuclear import of HIV-1 via the Vpr-Importin α interaction, suggesting that a specific inhibitor of the interaction between viral protein and the cellular factor may provide a new strategy for HIV-1 therapy.

  1. Artificial 64-Residue HIV-1 Enhancer-Binding Peptide Is a Potent Inhibitor of Viral Replication in HIV-1-Infected Cells.

    Science.gov (United States)

    Oufir, Mouhssin; Bisset, Leslie R; Hoffmann, Stefan R K; Xue, Gongda; Klauser, Stephan; Bergamaschi, Bianca; Gervaix, Alain; Böni, Jürg; Schüpbach, Jörg; Gutte, Bernd

    2011-01-01

    An artificial HIV-1 enhancer-binding peptide was extended by nine consecutive arginine residues at the C-terminus and by the nuclear localization signal of SV40 large T antigen at the N-terminus. The resulting synthetic 64-residue peptide was found to bind to the two enhancers of the HIV-1 long terminal repeat, cross the plasma membrane and the nuclear envelope of human cells, and suppress the HIV-1 enhancer-controlled expression of a green fluorescent protein reporter gene. Moreover, HIV-1 replication is inhibited by this peptide in HIV-1-infected CEM-GFP cells as revealed by HIV-1 p24 ELISA and real-time RT-PCR of HIV-1 RNA. Rapid uptake of this intracellular stable and inhibitory peptide into the cells implies that this peptide may have the potential to attenuate HIV-1 replication in vivo.

  2. Digoxin reveals a functional connection between HIV-1 integration preference and T-cell activation.

    Directory of Open Access Journals (Sweden)

    Alexander Zhyvoloup

    2017-07-01

    Full Text Available HIV-1 integrates more frequently into transcribed genes, however the biological significance of HIV-1 integration targeting has remained elusive. Using a selective high-throughput chemical screen, we discovered that the cardiac glycoside digoxin inhibits wild-type HIV-1 infection more potently than HIV-1 bearing a single point mutation (N74D in the capsid protein. We confirmed that digoxin repressed viral gene expression by targeting the cellular Na+/K+ ATPase, but this did not explain its selectivity. Parallel RNAseq and integration mapping in infected cells demonstrated that digoxin inhibited expression of genes involved in T-cell activation and cell metabolism. Analysis of >400,000 unique integration sites showed that WT virus integrated more frequently than N74D mutant within or near genes susceptible to repression by digoxin and involved in T-cell activation and cell metabolism. Two main gene networks down-regulated by the drug were CD40L and CD38. Blocking CD40L by neutralizing antibodies selectively inhibited WT virus infection, phenocopying digoxin. Thus the selectivity of digoxin depends on a combination of integration targeting and repression of specific gene networks. The drug unmasked a functional connection between HIV-1 integration and T-cell activation. Our results suggest that HIV-1 evolved integration site selection to couple its early gene expression with the status of target CD4+ T-cells, which may affect latency and viral reactivation.

  3. Digoxin reveals a functional connection between HIV-1 integration preference and T-cell activation.

    Science.gov (United States)

    Zhyvoloup, Alexander; Melamed, Anat; Anderson, Ian; Planas, Delphine; Lee, Chen-Hsuin; Kriston-Vizi, Janos; Ketteler, Robin; Merritt, Andy; Routy, Jean-Pierre; Ancuta, Petronela; Bangham, Charles R M; Fassati, Ariberto

    2017-07-01

    HIV-1 integrates more frequently into transcribed genes, however the biological significance of HIV-1 integration targeting has remained elusive. Using a selective high-throughput chemical screen, we discovered that the cardiac glycoside digoxin inhibits wild-type HIV-1 infection more potently than HIV-1 bearing a single point mutation (N74D) in the capsid protein. We confirmed that digoxin repressed viral gene expression by targeting the cellular Na+/K+ ATPase, but this did not explain its selectivity. Parallel RNAseq and integration mapping in infected cells demonstrated that digoxin inhibited expression of genes involved in T-cell activation and cell metabolism. Analysis of >400,000 unique integration sites showed that WT virus integrated more frequently than N74D mutant within or near genes susceptible to repression by digoxin and involved in T-cell activation and cell metabolism. Two main gene networks down-regulated by the drug were CD40L and CD38. Blocking CD40L by neutralizing antibodies selectively inhibited WT virus infection, phenocopying digoxin. Thus the selectivity of digoxin depends on a combination of integration targeting and repression of specific gene networks. The drug unmasked a functional connection between HIV-1 integration and T-cell activation. Our results suggest that HIV-1 evolved integration site selection to couple its early gene expression with the status of target CD4+ T-cells, which may affect latency and viral reactivation.

  4. Sexual risk behaviors among HIV-infected South African men and women with their partners in a primary care program: implications for couples-based prevention.

    Science.gov (United States)

    Venkatesh, Kartik K; de Bruyn, Guy; Lurie, Mark N; Modisenyane, Tebogo; Triche, Elizabeth W; Gray, Glenda E; Welte, Alex; Martinson, Neil A

    2012-01-01

    We studied 1163 sexually-active HIV-infected South African men and women in an urban primary care program to understand patterns of sexual behaviors and whether these behaviors differed by partner HIV status. Overall, 40% reported a HIV-positive partner and 60% a HIV-negative or status unknown partner; and 17.5% reported >2 sex acts in the last 2 weeks, 16.4% unprotected sex in the last 6 months, and 3.7% >1 sex partner in the last 6 months. Antiretroviral therapy (ART) was consistently associated with decreased sexual risk behaviors, as well as with reporting a HIV-negative or status unknown partner. The odds of sexual risk behaviors differed by sex; and were generally higher among participants reporting a HIV-positive partner, but continued among those with a HIV-negative or status unknown partner. These data support ART as a means of HIV prevention. Engaging in sexual risk behaviors primarily with HIV-positive partners was not widely practiced in this setting, emphasizing the need for couples-based prevention.

  5. Picomolar dichotomous activity of gnidimacrin against HIV-1.

    Directory of Open Access Journals (Sweden)

    Li Huang

    Full Text Available Highly active antiretroviral therapy (HAART has offered a promising approach for controlling HIV-1 replication in infected individuals. However, with HARRT, HIV-1 is suppressed rather than eradicated due to persistence of HIV-1 in latent viral reservoirs. Thus, purging the virus from latent reservoirs is an important strategy toward eradicating HIV-1 infection. In this study, we discovered that the daphnane diterpene gnidimacrin, which was previously reported to have potent anti-cancer cell activity, activated HIV-1 replication and killed persistently-infected cells at picomolar concentrations. In addition to its potential to purge HIV-1 from latently infected cells, gnidimacrin potently inhibited a panel of HIV-1 R5 virus infection of peripheral blood mononuclear cells (PBMCs at an average concentration lower than 10 pM. In contrast, gnidimacrin only partially inhibited HIV-1 ×4 virus infection of PBMCs. The strong anti-HIV-1 R5 virus activity of gnidimacrin was correlated with its effect on down-regulation of the HIV-1 coreceptor CCR5. The anti-R5 virus activity of gnidimacrin was completely abrogated by a selective protein kinase C beta inhibitor enzastaurin, which suggests that protein kinase C beta plays a key role in the potent anti-HIV-1 activity of gnidimacrin in PBMCs. In summary, these results suggest that gnidimacrin could activate latent HIV-1, specifically kill HIV-1 persistently infected cells, and inhibit R5 viruses at picomolar concentrations.

  6. HIV-1 envelope glycoprotein

    Science.gov (United States)

    Caulfield, Michael; Cupo, Albert; Dean, Hansi; Hoffenberg, Simon; King, C. Richter; Klasse, P. J.; Marozsan, Andre; Moore, John P.; Sanders, Rogier W.; Ward, Andrew; Wilson, Ian; Julien, Jean-Philippe

    2017-08-22

    The present application relates to novel HIV-1 envelope glycoproteins, which may be utilized as HIV-1 vaccine immunogens, and antigens for crystallization, electron microscopy and other biophysical, biochemical and immunological studies for the identification of broad neutralizing antibodies. The present invention encompasses the preparation and purification of immunogenic compositions, which are formulated into the vaccines of the present invention.

  7. Artificial 64-Residue HIV-1 Enhancer-Binding Peptide Is a Potent Inhibitor of Viral Replication in HIV-1-Infected Cells

    Directory of Open Access Journals (Sweden)

    Mouhssin Oufir

    2011-01-01

    Full Text Available An artificial HIV-1 enhancer-binding peptide was extended by nine consecutive arginine residues at the C-terminus and by the nuclear localization signal of SV40 large T antigen at the N-terminus. The resulting synthetic 64-residue peptide was found to bind to the two enhancers of the HIV-1 long terminal repeat, cross the plasma membrane and the nuclear envelope of human cells, and suppress the HIV-1 enhancer-controlled expression of a green fluorescent protein reporter gene. Moreover, HIV-1 replication is inhibited by this peptide in HIV-1-infected CEM-GFP cells as revealed by HIV-1 p24 ELISA and real-time RT-PCR of HIV-1 RNA. Rapid uptake of this intracellular stable and inhibitory peptide into the cells implies that this peptide may have the potential to attenuate HIV-1 replication in vivo.

  8. BI-2 destabilizes HIV-1 cores during infection and Prevents Binding of CPSF6 to the HIV-1 Capsid.

    Science.gov (United States)

    Fricke, Thomas; Buffone, Cindy; Opp, Silvana; Valle-Casuso, Jose; Diaz-Griffero, Felipe

    2014-12-11

    The recently discovered small-molecule BI-2 potently blocks HIV-1 infection. BI-2 binds to the N-terminal domain of HIV-1 capsid. BI-2 utilizes the same capsid pocket used by the small molecule PF74. Although both drugs bind to the same pocket, it has been proposed that BI-2 uses a different mechanism to block HIV-1 infection when compared to PF74. This work demonstrates that BI-2 destabilizes the HIV-1 core during infection, and prevents the binding of the cellular factor CPSF6 to the HIV-1 core. Overall this short-form paper suggests that BI-2 is using a similar mechanism to the one used by PF74 to block HIV-1 infection.

  9. Maturation of the viral core enhances the fusion of HIV-1 particles with primary human T cells and monocyte-derived macrophages

    International Nuclear Information System (INIS)

    Jiang Jiyang; Aiken, Christopher

    2006-01-01

    HIV-1 infection requires fusion of viral and cellular membranes in a reaction catalyzed by the viral envelope proteins gp120 and gp41. We recently reported that efficient HIV-1 particle fusion with target cells is linked to maturation of the viral core by an activity of the gp41 cytoplasmic domain. Here, we show that maturation enhances the fusion of a variety of recombinant viruses bearing primary and laboratory-adapted Env proteins with primary human CD4 + T cells. Overall, HIV-1 fusion was more dependent on maturation for viruses bearing X4-tropic envelope proteins than for R5-tropic viruses. Fusion of HIV-1 with monocyte-derived macrophages was also dependent on particle maturation. We conclude that the ability to couple fusion to particle maturation is a common feature of HIV-1 Env proteins and may play an important role during HIV-1 replication in vivo

  10. Phylogenetic analysis of HIV-1 pol gene: first subgenomic evidence of CRF29-BF among Iranian HIV-1 patients

    Directory of Open Access Journals (Sweden)

    Kazem Baesi

    2014-09-01

    Full Text Available Objective: To identify the dominant subtype among the HIV-1 strains circulation in Iran. Methods: In this cross sectional study 100 HIV positive patients participated. HIV-1 RNA was extracted from plasma. RT nested-PCR was performed and the final products were sequenced and phylogenetically analyzed; reference sequences were downloaded from Los Alamos, aligned with Iranian pol sequences in the study and analyzed by neighbor-joining method. Results: The results of the phylogenetic analysis showed that HIV-1 subtype CRF-35AD was the dominant subtype among HIV-1 infected patients in Iran; this analysis also suggested a new circulating recombinant form that had not previously been identified in Iran: CRF-29BF. Conclusions: The impact of HIV diversity on pathogenesis, transmission and clinical management have been discussed in different studies; therefore, analyses of HIV genetic diversity is required to design effective antiretroviral strategies for different HIV subtypes.

  11. Polyclonal B cell differentiation and loss of gastrointestinal tract germinal centers in the earliest stages of HIV-1 infection.

    Directory of Open Access Journals (Sweden)

    Marc C Levesque

    2009-07-01

    Full Text Available The antibody response to HIV-1 does not appear in the plasma until approximately 2-5 weeks after transmission, and neutralizing antibodies to autologous HIV-1 generally do not become detectable until 12 weeks or more after transmission. Moreover, levels of HIV-1-specific antibodies decline on antiretroviral treatment. The mechanisms of this delay in the appearance of anti-HIV-1 antibodies and of their subsequent rapid decline are not known. While the effect of HIV-1 on depletion of gut CD4(+ T cells in acute HIV-1 infection is well described, we studied blood and tissue B cells soon after infection to determine the effect of early HIV-1 on these cells.In human participants, we analyzed B cells in blood as early as 17 days after HIV-1 infection, and in terminal ileum inductive and effector microenvironments beginning at 47 days after infection. We found that HIV-1 infection rapidly induced polyclonal activation and terminal differentiation of B cells in blood and in gut-associated lymphoid tissue (GALT B cells. The specificities of antibodies produced by GALT memory B cells in acute HIV-1 infection (AHI included not only HIV-1-specific antibodies, but also influenza-specific and autoreactive antibodies, indicating very early onset of HIV-1-induced polyclonal B cell activation. Follicular damage or germinal center loss in terminal ileum Peyer's patches was seen with 88% of follicles exhibiting B or T cell apoptosis and follicular lysis.Early induction of polyclonal B cell differentiation, coupled with follicular damage and germinal center loss soon after HIV-1 infection, may explain both the high rate of decline in HIV-1-induced antibody responses and the delay in plasma antibody responses to HIV-1. Please see later in the article for Editors' Summary.

  12. Using a network-based approach and targeted maximum likelihood estimation to evaluate the effect of adding pre-exposure prophylaxis to an ongoing test-and-treat trial.

    Science.gov (United States)

    Balzer, Laura; Staples, Patrick; Onnela, Jukka-Pekka; DeGruttola, Victor

    2017-04-01

    Several cluster-randomized trials are underway to investigate the implementation and effectiveness of a universal test-and-treat strategy on the HIV epidemic in sub-Saharan Africa. We consider nesting studies of pre-exposure prophylaxis within these trials. Pre-exposure prophylaxis is a general strategy where high-risk HIV- persons take antiretrovirals daily to reduce their risk of infection from exposure to HIV. We address how to target pre-exposure prophylaxis to high-risk groups and how to maximize power to detect the individual and combined effects of universal test-and-treat and pre-exposure prophylaxis strategies. We simulated 1000 trials, each consisting of 32 villages with 200 individuals per village. At baseline, we randomized the universal test-and-treat strategy. Then, after 3 years of follow-up, we considered four strategies for targeting pre-exposure prophylaxis: (1) all HIV- individuals who self-identify as high risk, (2) all HIV- individuals who are identified by their HIV+ partner (serodiscordant couples), (3) highly connected HIV- individuals, and (4) the HIV- contacts of a newly diagnosed HIV+ individual (a ring-based strategy). We explored two possible trial designs, and all villages were followed for a total of 7 years. For each village in a trial, we used a stochastic block model to generate bipartite (male-female) networks and simulated an agent-based epidemic process on these networks. We estimated the individual and combined intervention effects with a novel targeted maximum likelihood estimator, which used cross-validation to data-adaptively select from a pre-specified library the candidate estimator that maximized the efficiency of the analysis. The universal test-and-treat strategy reduced the 3-year cumulative HIV incidence by 4.0% on average. The impact of each pre-exposure prophylaxis strategy on the 4-year cumulative HIV incidence varied by the coverage of the universal test-and-treat strategy with lower coverage resulting in a larger

  13. German-austrian recommendations for HIV1-therapy in pregnancy and in HIV1-exposed newborn - update 2008

    Directory of Open Access Journals (Sweden)

    Buchholz Bernd

    2009-11-01

    Full Text Available Abstract German-Austrian recommendations for HIV1-therapy in pregnancy - Update 2008 Bernd Buchholz (University Medical Centre Mannheim, Pediatric Clinic, Matthias Beichert (Mannheim, Gynecology and Obstetrics Practice, Ulrich Marcus (Robert Koch Institute, Berlin, Thomas Grubert, Andrea Gingelmaier (Gynecology Clinic of the Ludwig Maximilians University of Munich, Dr. med. Annette Haberl (HIV-Department, J. W. Goethe-University Hospital, Frankfurt, Dr. med. Brigitte Schmied (Otto-Wagner Spital, Wien. In Germany during the last years about 200-250 HIV1-infected pregnant women delivered a baby each year, a number that is currently increasing. To determine the HIV-status early in pregnancy voluntary HIV-testing of all pregnant women is recommended in Germany and Austria as part of prenatal care. In those cases, where HIV1-infection was known during pregnancy, since 1995 the rate of vertical transmission of HIV1 was reduced to 1-2%. This low transmission rate has been achieved by the combination of anti-retroviral therapy of pregnant women, caesarean section scheduled before onset of labour, anti-retroviral post exposition prophylaxis in the newborn and refraining from breast-feeding by the HIV1-infected mother. To keep pace with new results in research, approval of new anti-retroviral drugs and changes in the general treatment recommendations for HIV1-infected adults, in 1998, 2001, 2003 and 2005 an interdisciplinary consensus meeting was held. Gynaecologists, infectious disease specialists, paediatricians, pharmacologists, virologists and members of the German AIDS Hilfe (NGO were participating in this conference to update the prevention strategies. A fifth update became necessary in 2008. The updating process was started in January 2008 and was terminated in September 2008. The guidelines provide new recommendations on the indication and the starting point for HIV-therapy in pregnancies without complications, drugs and drug combinations to be

  14. DBR1 siRNA inhibition of HIV-1 replication

    Directory of Open Access Journals (Sweden)

    Naidu Yathi

    2005-10-01

    Full Text Available Abstract Background HIV-1 and all retroviruses are related to retroelements of simpler organisms such as the yeast Ty elements. Recent work has suggested that the yeast retroelement Ty1 replicates via an unexpected RNA lariat intermediate in cDNA synthesis. The putative genomic RNA lariat intermediate is formed by a 2'-5' phosphodiester bond, like that found in pre-mRNA intron lariats and it facilitates the minus-strand template switch during cDNA synthesis. We hypothesized that HIV-1 might also form a genomic RNA lariat and therefore that siRNA-mediated inhibition of expression of the human RNA lariat de-branching enzyme (DBR1 expression would specifically inhibit HIV-1 replication. Results We designed three short interfering RNA (siRNA molecules targeting DBR1, which were capable of reducing DBR1 mRNA expression by 80% and did not significantly affect cell viability. We assessed HIV-1 replication in the presence of DBR1 siRNA and found that DBR1 knockdown led to decreases in viral cDNA and protein production. These effects could be reversed by cotransfection of a DBR1 cDNA indicating that the inhibition of HIV-1 replication was a specific effect of DBR1 underexpression. Conclusion These data suggest that DBR1 function may be needed to debranch a putative HIV-1 genomic RNA lariat prior to completion of reverse transcription.

  15. Genetic Signatures of HIV-1 Envelope-mediated Bystander Apoptosis

    Science.gov (United States)

    Joshi, Anjali; Lee, Raphael T. C.; Mohl, Jonathan; Sedano, Melina; Khong, Wei Xin; Ng, Oon Tek; Maurer-Stroh, Sebastian; Garg, Himanshu

    2014-01-01

    The envelope (Env) glycoprotein of HIV is an important determinant of viral pathogenesis. Several lines of evidence support the role of HIV-1 Env in inducing bystander apoptosis that may be a contributing factor in CD4+ T cell loss. However, most of the studies testing this phenomenon have been conducted with laboratory-adapted HIV-1 isolates. This raises the question of whether primary Envs derived from HIV-infected patients are capable of inducing bystander apoptosis and whether specific Env signatures are associated with this phenomenon. We developed a high throughput assay to determine the bystander apoptosis inducing activity of a panel of primary Envs. We tested 38 different Envs for bystander apoptosis, virion infectivity, neutralizing antibody sensitivity, and putative N-linked glycosylation sites along with a comprehensive sequence analysis to determine if specific sequence signatures within the viral Env are associated with bystander apoptosis. Our studies show that primary Envs vary considerably in their bystander apoptosis-inducing potential, a phenomenon that correlates inversely with putative N-linked glycosylation sites and positively with virion infectivity. By use of a novel phylogenetic analysis that avoids subtype bias coupled with structural considerations, we found specific residues like Arg-476 and Asn-425 that were associated with differences in bystander apoptosis induction. A specific role of these residues was also confirmed experimentally. These data demonstrate for the first time the potential of primary R5 Envs to mediate bystander apoptosis in CD4+ T cells. Furthermore, we identify specific genetic signatures within the Env that may be associated with the bystander apoptosis-inducing phenotype. PMID:24265318

  16. HLA Class I-Mediated HIV-1 Control in Vietnamese Infected with HIV-1 Subtype A/E.

    Science.gov (United States)

    Chikata, Takayuki; Tran, Giang Van; Murakoshi, Hayato; Akahoshi, Tomohiro; Qi, Ying; Naranbhai, Vivek; Kuse, Nozomi; Tamura, Yoshiko; Koyanagi, Madoka; Sakai, Sachiko; Nguyen, Dung Hoai; Nguyen, Dung Thi; Nguyen, Ha Thu; Nguyen, Trung Vu; Oka, Shinichi; Martin, Maureen P; Carrington, Mary; Sakai, Keiko; Nguyen, Kinh Van; Takiguchi, Masafumi

    2018-03-01

    HIV-1-specific cytotoxic T cells (CTLs) play an important role in the control of HIV-1 subtype B or C infection. However, the role of CTLs in HIV-1 subtype A/E infection still remains unclear. Here we investigated the association of HLA class I alleles with clinical outcomes in treatment-naive Vietnamese infected with subtype A/E virus. We found that HLA-C*12:02 was significantly associated with lower plasma viral loads (pVL) and higher CD4 counts and that the HLA-A*29:01-B*07:05-C*15:05 haplotype was significantly associated with higher pVL and lower CD4 counts than those for individuals without these respective genotypes. Nine Pol and three Nef mutations were associated with at least one HLA allele in the HLA-A*29:01-B*07:05-C*15:05 haplotype, with a strong negative correlation between the number of HLA-associated Pol mutations and CD4 count as well as a positive correlation with pVL for individuals with these HLA alleles. The results suggest that the accumulation of mutations selected by CTLs restricted by these HLA alleles affects HIV control. IMPORTANCE Most previous studies on HLA association with disease progression after HIV-1 infection have been performed on cohorts infected with HIV-1 subtypes B and C, whereas few such population-based studies have been reported for cohorts infected with the Asian subtype A/E virus. In this study, we analyzed the association of HLA class I alleles with clinical outcomes for 536 HIV-1 subtype A/E-infected Vietnamese individuals. We found that HLA-C*12:02 is protective, while the HLA haplotype HLA-A*29:01-B*07:05-C*15:05 is deleterious. The individuals with HIV-1 mutations associated with at least one of the HLA alleles in the deleterious HLA haplotype had higher plasma viral loads and lower CD4 counts than those of individuals without the mutations, suggesting that viral adaptation and escape from HLA-mediated immune control occurred. The present study identifies a protective allele and a deleterious haplotype for HIV-1

  17. Differential effects of sex in a West African cohort of HIV-1, HIV-2 and HIV-1/2 dually infected patients: men are worse off.

    Science.gov (United States)

    Jespersen, Sanne; Hønge, Bo Langhoff; Esbjörnsson, Joakim; Medina, Candida; da Silva Té, David; Correira, Faustino Gomes; Laursen, Alex Lund; Østergaard, Lars; Andersen, Andreas; Aaby, Peter; Erikstrup, Christian; Wejse, Christian

    2016-02-01

    Several studies have reported conflicting effects of sex on HIV-1 infection. We describe differences in baseline characteristics and assess the impact of sex on HIV progression among patients at a clinic with many HIV-2 and HIV-1/2 dually infected patients. This study utilised a retrospective cohort of treatment-naïve adults at the largest HIV clinic in Guinea-Bissau from 6 June 2005 to 1 December 2013. Baseline characteristics were assessed and the patients followed until death, transfer, loss to follow-up, or 1 June 2014. We estimated the time from the first clinic visit until initiation of ART, death or loss to follow-up using Cox proportional hazard models. A total of 5694 patients were included in the study, 3702 women (65%) and 1992 men (35%). Women were more likely than men to be infected with HIV-2 (19% vs. 15%, P < 0.01) or dually infected with HIV-1/2 (11% vs. 9%, P = 0.02). For all HIV types, women were younger (median 35 vs. 40 years), less likely to have schooling (55% vs. 77%) or to be married (46% vs. 67%), and had higher baseline CD4 cell counts (median 214 vs. 178 cells/μl). Men had a higher age-adjusted mortality rate (hazard rate ratio (HRR) 1.29, 95% confidence interval (CI) 1.09-1.52) and were more often lost to follow-up (HRR 1.27, 95% CI 1.17-1.39). Significant differences exist between HIV-infected men and women regardless of HIV type. Men seek treatment at a later stage and, despite better socio-economic status, have higher mortality and loss to follow-up than women. © 2015 John Wiley & Sons Ltd.

  18. Systemic administration of antiretrovirals prior to exposure prevents rectal and intravenous HIV-1 transmission in humanized BLT mice.

    Directory of Open Access Journals (Sweden)

    Paul W Denton

    2010-01-01

    Full Text Available Successful antiretroviral pre-exposure prophylaxis (PrEP for mucosal and intravenous HIV-1 transmission could reduce new infections among targeted high-risk populations including discordant couples, injection drug users, high-risk women and men who have sex with men. Targeted antiretroviral PrEP could be particularly effective at slowing the spread of HIV-1 if a single antiretroviral combination were found to be broadly protective across multiple routes of transmission. Therefore, we designed our in vivo preclinical study to systematically investigate whether rectal and intravenous HIV-1 transmission can be blocked by antiretrovirals administered systemically prior to HIV-1 exposure. We performed these studies using a highly relevant in vivo model of mucosal HIV-1 transmission, humanized Bone marrow/Liver/Thymus mice (BLT. BLT mice are susceptible to HIV-1 infection via three major physiological routes of viral transmission: vaginal, rectal and intravenous. Our results show that BLT mice given systemic antiretroviral PrEP are efficiently protected from HIV-1 infection regardless of the route of exposure. Specifically, systemic antiretroviral PrEP with emtricitabine and tenofovir disoproxil fumarate prevented both rectal (Chi square = 8.6, df = 1, p = 0.003 and intravenous (Chi square = 13, df = 1, p = 0.0003 HIV-1 transmission. Our results indicate that antiretroviral PrEP has the potential to be broadly effective at preventing new rectal or intravenous HIV transmissions in targeted high risk individuals. These in vivo preclinical findings provide strong experimental evidence supporting the potential clinical implementation of antiretroviral based pre-exposure prophylactic measures to prevent the spread of HIV/AIDS.

  19. Impact of marriage on HIV/AIDS risk behaviors among impoverished, at-risk couples: A multilevel latent variable approach

    OpenAIRE

    Stein, JA; Nyamathi, A; Ullman, JB; Bentler, PM

    2007-01-01

    Studies among normative samples generally demonstrate a positive impact of marriage on health behaviors and other related attitudes. In this study, we examine the impact of marriage on HIV/AIDS risk behaviors and attitudes among impoverished, highly stressed, homeless couples, many with severe substance abuse problems. A multilevel analysis of 368 high-risk sexually intimate married and unmarried heterosexual couples assessed individual and couple-level effects on social support, substance us...

  20. Effects of human SAMHD1 polymorphisms on HIV-1 susceptibility

    International Nuclear Information System (INIS)

    White, Tommy E.; Brandariz-Nuñez, Alberto; Valle-Casuso, Jose Carlos; Knowlton, Caitlin; Kim, Baek; Sawyer, Sara L.; Diaz-Griffero, Felipe

    2014-01-01

    SAMHD1 is a human restriction factor that prevents efficient infection of macrophages, dendritic cells and resting CD4+ T cells by HIV-1. Here we explored the antiviral activity and biochemical properties of human SAMHD1 polymorphisms. Our studies focused on human SAMHD1 polymorphisms that were previously identified as evolving under positive selection for rapid amino acid replacement during primate speciation. The different human SAMHD1 polymorphisms were tested for their ability to block HIV-1, HIV-2 and equine infectious anemia virus (EIAV). All studied SAMHD1 variants block HIV-1, HIV-2 and EIAV infection when compared to wild type. We found that these variants did not lose their ability to oligomerize or to bind RNA. Furthermore, all tested variants were susceptible to degradation by Vpx, and localized to the nuclear compartment. We tested the ability of human SAMHD1 polymorphisms to decrease the dNTP cellular levels. In agreement, none of the different SAMHD1 variants lost their ability to reduce cellular levels of dNTPs. Finally, we found that none of the tested human SAMHD1 polymorphisms affected the ability of the protein to block LINE-1 retrotransposition. - Highlights: • Human SAMHD1 single-nucleotide polymorphisms block HIV-1 and HIV-2 infection. • SAMHD1 polymorphisms do not affect its ability to block LINE-1 retrotransposition. • SAMHD1 polymorphisms decrease the cellular levels of dNTPs

  1. Effects of human SAMHD1 polymorphisms on HIV-1 susceptibility

    Energy Technology Data Exchange (ETDEWEB)

    White, Tommy E.; Brandariz-Nuñez, Alberto; Valle-Casuso, Jose Carlos [Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, 1301 Morris Park – Price Center 501, New York, NY 10461 (United States); Knowlton, Caitlin; Kim, Baek [Department of Microbiology and Immunology, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642 (United States); Sawyer, Sara L. [Department of Molecular Biosciences, University of Texas at Austin, Austin, TX 78712 (United States); Diaz-Griffero, Felipe, E-mail: Felipe.Diaz-Griffero@einstein.yu.edu [Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, 1301 Morris Park – Price Center 501, New York, NY 10461 (United States)

    2014-07-15

    SAMHD1 is a human restriction factor that prevents efficient infection of macrophages, dendritic cells and resting CD4+ T cells by HIV-1. Here we explored the antiviral activity and biochemical properties of human SAMHD1 polymorphisms. Our studies focused on human SAMHD1 polymorphisms that were previously identified as evolving under positive selection for rapid amino acid replacement during primate speciation. The different human SAMHD1 polymorphisms were tested for their ability to block HIV-1, HIV-2 and equine infectious anemia virus (EIAV). All studied SAMHD1 variants block HIV-1, HIV-2 and EIAV infection when compared to wild type. We found that these variants did not lose their ability to oligomerize or to bind RNA. Furthermore, all tested variants were susceptible to degradation by Vpx, and localized to the nuclear compartment. We tested the ability of human SAMHD1 polymorphisms to decrease the dNTP cellular levels. In agreement, none of the different SAMHD1 variants lost their ability to reduce cellular levels of dNTPs. Finally, we found that none of the tested human SAMHD1 polymorphisms affected the ability of the protein to block LINE-1 retrotransposition. - Highlights: • Human SAMHD1 single-nucleotide polymorphisms block HIV-1 and HIV-2 infection. • SAMHD1 polymorphisms do not affect its ability to block LINE-1 retrotransposition. • SAMHD1 polymorphisms decrease the cellular levels of dNTPs.

  2. High HIV Prevalence and Risk Among Male Clients of Female Sex Workers in Hanoi and Ho Chi Minh City, Vietnam.

    Science.gov (United States)

    Nadol, Patrick; Hoang, Tran Vu; Le, Linh-Vi; Nguyen, Tuan Anh; Kaldor, John; Law, Matthew

    2017-08-01

    In Vietnam's concentrated HIV epidemic, female sex workers (FSWs) are at increased risk for acquiring and transmitting HIV, largely through their male clients. A high proportion of males in Vietnam report being clients of FSWs. Studying HIV-related risk factors and prevalence among male clients is important, particularly given the potential for male clients to be a 'bridge' of HIV transmission to the more general population or to sex workers. Time-location sampling was used to identify FSW in Hanoi and Ho Chi Minh City, Vietnam's largest cities, in 2013-2014. Recruited FSWs were asked to refer one male client to the study. Demographic and risk behavior data were collected from FSWs and male clients by administered questionnaires. Biologic specimens collected from male clients were tested for HIV and opiates. Sampling weights, calculated based on the FSWs probability of being selected for enrolment, were applied to prevalence estimates for both FSWs and male clients. Logistic regression models were developed to obtain odds ratios for HIV infection among male clients. A total of 804 male clients were enrolled. Overall, HIV prevalence among male clients was 10.2%; HIV prevalence was 20.7% (95% confidence interval (CI) 15.0-27.9%) among those reporting a history of illegal drug use and 32.4% (95% CI 20.2-47.7%) among those with opioids detected in urine. HIV prevalence among male clients did not differ across 'bridging' categories defined by condom use with FSWs and regular partners over the previous 6 months. HIV among male clients was associated with a reported history of illegal drug use (OR 3.76; 95% CI 1.87-7.56), current opioid use (OR 2.55; 95% CI 1.02-6.36), and being referred by an FSW who self-reported as HIV-positive (OR 5.37; 95% CI 1.46-19.75). Self-reported HIV prevalence among enrolled FSWs was 2.8%. Based on HIV test results of male clients and self-reported status from FSWs, an estimated 12.1% of male client-FSW pairs were sero-discordant. These

  3. Cyclophilin B enhances HIV-1 infection

    Energy Technology Data Exchange (ETDEWEB)

    DeBoer, Jason; Madson, Christian J. [Department of Medical Microbiology and Immunology, Creighton University, Omaha, NE (United States); Belshan, Michael, E-mail: michaelbelshan@creighton.edu [Department of Medical Microbiology and Immunology, Creighton University, Omaha, NE (United States); The Nebraska Center for Virology, University of Nebraska, Lincoln, NE (United States)

    2016-02-15

    Cyclophilin B (CypB) is a member of the immunophilin family and intracellular chaperone. It predominantly localizes to the ER, but also contains a nuclear localization signal and is secreted from cells. CypB has been shown to interact with the Gag protein of human immunodeficiency type 1 (HIV-1). Several proteomic and genetic studies identified it as a potential factor involved in HIV replication. Herein, we show that over-expression of CypB enhances HIV infection by increasing nuclear import of viral DNA. This enhancement was unaffected by cyclosporine treatment and requires the N-terminus of the protein. The N-terminus contains an ER leader sequence, putative nuclear localization signal, and is required for secretion. Deletion of the N-terminus resulted in mislocalization from the ER and suppression of HIV infection. Passive transfer experiments showed that secreted CypB did not impact HIV infection. Combined, these experiments show that intracellular CypB modulates a pathway of HIV nuclear import. - Highlights: • CypB has been identified in several proteomic studies of HIV-1 infection. • CypB expression is upregulated in activated and infected T-cells. • Over-expression of CypB enhances HIV nuclear import and infection. • The N-terminus of CypB is necessary for these effects.

  4. Cyclophilin B enhances HIV-1 infection

    International Nuclear Information System (INIS)

    DeBoer, Jason; Madson, Christian J.; Belshan, Michael

    2016-01-01

    Cyclophilin B (CypB) is a member of the immunophilin family and intracellular chaperone. It predominantly localizes to the ER, but also contains a nuclear localization signal and is secreted from cells. CypB has been shown to interact with the Gag protein of human immunodeficiency type 1 (HIV-1). Several proteomic and genetic studies identified it as a potential factor involved in HIV replication. Herein, we show that over-expression of CypB enhances HIV infection by increasing nuclear import of viral DNA. This enhancement was unaffected by cyclosporine treatment and requires the N-terminus of the protein. The N-terminus contains an ER leader sequence, putative nuclear localization signal, and is required for secretion. Deletion of the N-terminus resulted in mislocalization from the ER and suppression of HIV infection. Passive transfer experiments showed that secreted CypB did not impact HIV infection. Combined, these experiments show that intracellular CypB modulates a pathway of HIV nuclear import. - Highlights: • CypB has been identified in several proteomic studies of HIV-1 infection. • CypB expression is upregulated in activated and infected T-cells. • Over-expression of CypB enhances HIV nuclear import and infection. • The N-terminus of CypB is necessary for these effects.

  5. Enrichment of intersubtype HIV-1 recombinants in a dual infection system using HIV-1 strain-specific siRNAs

    Science.gov (United States)

    2011-01-01

    Background Intersubtype HIV-1 recombinants in the form of unique or stable circulating recombinants forms (CRFs) are responsible for over 20% of infections in the worldwide epidemic. Mechanisms controlling the generation, selection, and transmission of these intersubtype HIV-1 recombinants still require further investigation. All intersubtype HIV-1 recombinants are generated and evolve from initial dual infections, but are difficult to identify in the human population. In vitro studies provide the most practical system to study mechanisms, but the recombination rates are usually very low in dual infections with primary HIV-1 isolates. This study describes the use of HIV-1 isolate-specific siRNAs to enrich intersubtype HIV-1 recombinants and inhibit the parental HIV-1 isolates from a dual infection. Results Following a dual infection with subtype A and D primary HIV-1 isolates and two rounds of siRNA treatment, nearly 100% of replicative virus was resistant to a siRNA specific for an upstream target sequence in the subtype A envelope (env) gene as well as a siRNA specific for a downstream target sequence in the subtype D env gene. Only 20% (10/50) of the replicating virus had nucleotide substitutions in the siRNA-target sequence whereas the remaining 78% (39/50) harbored a recombination breakpoint that removed both siRNA target sequences, and rendered the intersubtype D/A recombinant virus resistant to the dual siRNA treatment. Since siRNAs target the newly transcribed HIV-1 mRNA, the siRNAs only enrich intersubtype env recombinants and do not influence the recombination process during reverse transcription. Using this system, a strong bias is selected for recombination breakpoints in the C2 region, whereas other HIV-1 env regions, most notably the hypervariable regions, were nearly devoid of intersubtype recombination breakpoints. Sequence conservation plays an important role in selecting for recombination breakpoints, but the lack of breakpoints in many conserved

  6. Mother-to-Child HIV-1 Transmission Events Are Differentially Impacted by Breast Milk and Its Components from HIV-1-Infected Women.

    Directory of Open Access Journals (Sweden)

    Ruizhong Shen

    Full Text Available Breast milk is a vehicle of infection and source of protection in post-natal mother-to-child HIV-1 transmission (MTCT. Understanding the mechanism by which breast milk limits vertical transmission will provide critical insight into the design of preventive and therapeutic approaches to interrupt HIV-1 mucosal transmission. However, characterization of the inhibitory activity of breast milk in human intestinal mucosa, the portal of entry in postnatal MTCT, has been constrained by the limited availability of primary mucosal target cells and tissues to recapitulate mucosal transmission ex vivo. Here, we characterized the impact of skimmed breast milk, breast milk antibodies (Igs and non-Ig components from HIV-1-infected Ugandan women on the major events of HIV-1 mucosal transmission using primary human intestinal cells and tissues. HIV-1-specific IgG antibodies and non-Ig components in breast milk inhibited the uptake of Ugandan HIV-1 isolates by primary human intestinal epithelial cells, viral replication in and transport of HIV-1- bearing dendritic cells through the human intestinal mucosa. Breast milk HIV-1-specific IgG and IgA, as well as innate factors, blocked the uptake and transport of HIV-1 through intestinal mucosa. Thus, breast milk components have distinct and complementary effects in reducing HIV-1 uptake, transport through and replication in the intestinal mucosa and, therefore, likely contribute to preventing postnatal HIV-1 transmission. Our data suggests that a successful preventive or therapeutic approach would require multiple immune factors acting at multiple steps in the HIV-1 mucosal transmission process.

  7. HIV-1 transgene expression in rats causes oxidant stress and alveolar epithelial barrier dysfunction

    Directory of Open Access Journals (Sweden)

    Jacob Barbara A

    2009-02-01

    Full Text Available Abstract Background HIV-infected individuals are at increased risk for acute and chronic airway disease even though there is no evidence that the virus can infect the lung epithelium. Although HIV-related proteins including gp120 and Tat can directly cause oxidant stress and cellular dysfunction, their effects in the lung are unknown. The goal of this study was to determine the effects of HIV-1 transgene expression in rats on alveolar epithelial barrier function. Alveolar epithelial barrier function was assessed by determining lung liquid clearance in vivo and alveolar epithelial monolayer permeability in vitro. Oxidant stress in the alveolar space was determined by measuring the glutathione redox couple by high performance liquid chromatography, and the expression and membrane localization of key tight junction proteins were assessed. Finally, the direct effects of the HIV-related proteins gp120 and Tat on alveolar epithelial barrier formation and tight junction protein expression were determined. Results HIV-1 transgene expression caused oxidant stress within the alveolar space and impaired epithelial barrier function even though there was no evidence of overt inflammation within the airways. The expression and membrane localization of the tight junction proteins zonula occludens-1 and occludin were decreased in alveolar epithelial cells from HIV-1 transgenic rats. Further, treating alveolar epithelial monolayers from wild type rats in vitro with recombinant gp120 or Tat for 24 hours reproduced many of the effects on zonula occludens-1 and occludin expression and membrane localization. Conclusion Taken together, these data indicate that HIV-related proteins cause oxidant stress and alter the expression of critical tight junction proteins in the alveolar epithelium, resulting in barrier dysfunction.

  8. Sexual Networks, Dyadic Characteristics, and HIV Acquisition and Transmission Behaviors Among Black Men Who Have Sex With Men in 6 US Cities.

    Science.gov (United States)

    Hickson, DeMarc A; Mena, Leandro A; Wilton, Leo; Tieu, Hong-Van; Koblin, Beryl A; Cummings, Vanessa; Latkin, Carl; Mayer, Kenneth H

    2017-05-01

    The role of sexual networks in the epidemiology of human immunodeficiency virus (HIV) among black men who have sex with men (MSM) is poorly understood. Using data from 1,306 black MSM in the BROTHERS Study (2009-2010) in the United States, we examined the relationships between multiple sexual dyadic characteristics and serodiscordant/serostatus-unknown condomless sex (SDCS). HIV-infected participants had higher odds of SDCS when having sex at least weekly (odds ratio (OR) = 2.41, 95% confidence interval (CI): 1.37, 4.23) or monthly (OR = 1.94, 95% CI: 1.17, 3.24) versus once to a few times a year. HIV-uninfected participants had higher odds of SDCS with partners met offline at sex-focused venues (OR = 1.79, 95% CI: 1.15, 2.78) versus partners met online. In addition, having sex upon first meeting was associated with higher odds of SDCS (OR = 1.49, 95% CI: 1.21, 1.83) than was not having sex on first meeting, while living/continued communication with sexual partner(s) was associated with lower odds of SDCS (weekly: OR = 0.64, 95% CI: 0.47, 0.85; monthly: OR = 0.60, 95% CI: 0.44, 0.81; yearly: OR = 0.58, 95% CI: 0.39, 0.85) versus discontinued communication. Persons with primary/steady nonprimary partners versus commercial partners had lower odds of SDCS regardless of HIV serostatus. This suggests the need for culturally relevant HIV prevention efforts for black MSM that facilitate communication with sexual partners especially about risk reduction strategies, including preexposure prophylaxis. © The Author 2017. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  9. HIV-1 Non-Nucleoside Reverse Transcriptase Inhibitors

    DEFF Research Database (Denmark)

    Vanangamudi, Murugesan; Poongavanam, Vasanthanathan; Namasivayam, Vigneshwaran

    2017-01-01

    BACKGROUND: Design of inhibitors for HIV-1 reverse transcriptase inhibition (HIV-1 RT) is one of the successful chemotherapies for the treatment of HIV infection. Among the inhibitors available for HIV-1 RT, non-nucleoside reverse transcriptase inhibitors (NNRTIs) have shown to be very promising......: The conformation dependent-alignment based (CoMFA and CoMSIA) methods have been proven very successful ligand based strategy in the drug design. Here, CoMFA and CoMSIA studies reported for structurally distinct NNRTIs including thiazolobenzimidazole, dipyridodiazepinone, 1,1,3-trioxo [1,2,4]-thiadiazine...

  10. Zinc status in HIV infected Ugandan children aged 1-5 years: a cross sectional baseline survey

    Directory of Open Access Journals (Sweden)

    Ndugwa Christopher M

    2010-09-01

    Full Text Available Abstract Background Low concentrations of serum zinc have been reported in HIV infected adults and are associated with disease progression and an increased risk of death. Few studies have been conducted in HIV infected children in Africa. We determined serum zinc levels and factors associated with zinc deficiency in HIV infected Ugandan children. Methods We measured the baseline zinc status of 247 children aged 1-5 years enrolled in a randomised trial for multiple micronutrient supplementation at paediatric HIV clinics in Uganda (http://ClinicalTrials.gov NCT00122941. Zinc status was determined using inductively coupled atomic emission spectrophotometry (ICP-AES. Clinical and laboratory characteristics were compared among zinc deficient (zinc Results Of the 247 children, 134 (54.3% had low serum zinc ( Conclusion Almost two thirds of HAART naïve and a third of HAART treated HIV infected children were zinc deficient. Increased access to HAART among HIV infected children living in Uganda might reduce the prevalence of zinc deficiency.

  11. A little thing called love: condom use in high-risk primary heterosexual relationships.

    Science.gov (United States)

    Corbett, A Michelle; Dickson-Gómez, Julia; Hilario, Helena; Weeks, Margaret R

    2009-12-01

    Condoms are less likely to be used in primary relationships than in other relationship types. An understanding of what women and men expect when entering into these relationships, as well as how they make decisions about condom use and other prevention behaviors, is essential to efforts to curb the spread of HIV. Qualitative in-depth interviews were conducted with 25 high-risk heterosexual couples, including HIV-serodiscordant couples, participating in a trial of the female condom in Hartford in 2004-2007. Data were coded and analyzed in an iterative inductive and deductive process. Participants described nonuse of condoms as a strategy to fi nd and maintain a primary relationship, establish trust and increase intimacy. Many had unprotected intercourse while recognizing their risk of HIV and other STDs, placing their love for their partner and other emotional needs over concerns about their health. Several couples reduced their STD risk by practicing negotiated safety (i.e., using condoms until their serostatus had been determined) or similar strategies, including sharing sexual or drug use history, disclosing HIV test results and using condoms until they decided that their relationship would be monogamous. HIV prevention approaches must recognize the importance of love and the needs that primary relationships satisfy if they are to be considered relevant by those at greatest risk. Negotiated safety and similar strategies may be an important risk reduction tool for heterosexuals, particularly those in HIV-affected relationships, but their potential effectiveness may vary.

  12. Perceptions and Definitions of Power Within the Context of HIV-Negative Male Couples’ Relationships

    OpenAIRE

    Mitchell, Jason W.; Sophus, Amber I.

    2016-01-01

    Examining dynamics within relationships is critical for development of effective HIV prevention interventions for male couples. The dynamic of power has received little attention in research with male couples, though power has been reported to affect HIV risk among heterosexual couples. To help address this knowledge gap, the present cross-sectional analysis used mixed methods with dyadic data from 142 HIV-negative male couples to (1) assess partnered men’s perception of who has the most powe...

  13. The cytosolic exonuclease TREX1 inhibits the innate immune response to HIV-1

    Science.gov (United States)

    Yan, Nan; Regalado-Magdos, Ashton D.; Stiggelbout, Bart; Lee-Kirsch, Min Ae; Lieberman, Judy

    2010-01-01

    Viral infection triggers innate immune sensors to produce type I interferons (IFN). However, HIV infection of T cells and macrophages does not trip these alarms. How HIV avoids activating nucleic acid sensors is unknown. The cytosolic exonuclease TREX1 suppressed IFN triggered by HIV. In Trex1−/− mouse cells and human CD4+ T cells and macrophages in which TREX1 was inhibited by RNA interference, cytosolic HIV DNA accumulated, and HIV infection induced type I IFN that inhibited HIV replication and spreading. TREX1 bound to cytosolic HIV DNA and digested excess HIV DNA that would otherwise activate IFN expression via a TBK1, STING and IRF3 dependent pathway. HIV-stimulated IFN production in cells deficient in TREX1 did not involve known nucleic acid sensors. PMID:20871604

  14. Cocaine modulates HIV-1 integration in primary CD4+ T cells: implications in HIV-1 pathogenesis in drug-abusing patients

    Science.gov (United States)

    Addai, Amma B.; Pandhare, Jui; Paromov, Victor; Mantri, Chinmay K.; Pratap, Siddharth; Dash, Chandravanu

    2015-01-01

    Epidemiologic studies suggest that cocaine abuse worsens HIV-1 disease progression. Increased viral load has been suggested to play a key role for the accelerated HIV disease among cocaine-abusing patients. The goal of this study was to investigate whether cocaine enhances proviral DNA integration as a mechanism to increase viral load. We infected CD4+ T cells that are the primary targets of HIV-1 in vivo and treated the cells with physiologically relevant concentrations of cocaine (1 µM–100 µM). Proviral DNA integration in the host genome was measured by nested qPCR. Our results illustrated that cocaine from 1 µM through 50 µM increased HIV-1 integration in CD4+ T cells in a dose-dependent manner. As integration can be modulated by several early postentry steps of HIV-1 infection, we examined the direct effects of cocaine on viral integration by in vitro integration assays by use of HIV-1 PICs. Our data illustrated that cocaine directly increases viral DNA integration. Furthermore, our MS analysis showed that cocaine is able to enter CD4+ T cells and localize to the nucleus-. In summary, our data provide strong evidence that cocaine can increase HIV-1 integration in CD4+ T cells. Therefore, we hypothesize that increased HIV-1 integration is a novel mechanism by which cocaine enhances viral load and worsens disease progression in drug-abusing HIV-1 patients. PMID:25691383

  15. Development of an HIV-1 Subtype Panel in China: Isolation and Characterization of 30 HIV-1 Primary Strains Circulating in China.

    Directory of Open Access Journals (Sweden)

    Jingwan Han

    Full Text Available The complex epidemic and significant diversity of HIV-1 strains in China pose serious challenges for surveillance and diagnostic assays, vaccine development and clinical management. There is a lack of HIV-1 isolates in current canonical HIV-1 subtype panels that can represent HIV-1 diversity in China; an HIV-1 subtype panel for China is urgently needed.Blood samples were collected from HIV-1 infected patients participating in the drug-resistance surveillance program in China. The samples were isolated, cultured and stored as neat culture supernatant. The HIV-1 isolates were fully characterized. The panel was used to compare 2 viral load assays and 2 p24 assays as the examples of how this panel could be used.An HIV-1 subtype panel for China composed of 30 HIV-1 primary strains of four subtypes (B [including Thai-B], CRF01_AE, CRF07_BC and G was established. The samples were isolated and cultured to a high-titer (10(6-10(9 copies/ml/high-volume (40 ml. The HIV-1 isolates were fully characterized by the final viral load, p24 concentration, gag-pol and envC2V3 sequencing, co-receptor prediction, determination of the four amino acids at the tip of the env V3-loop, glycosylation sites in the V3 loop and the drug-resistance mutations. The comparison of two p24 assays and two viral load assays on the isolates illustrated how this panel may be used for the evaluation of diagnostic assay performance. The Pearson value between p24 assays were 0.938. The viral load results showed excellent concordance and agreement for samples of Thai-B, but lower correlations for samples of CRF01_AE.The current panel of 30 HIV-1 isolates served as a basis for the development of a comprehensive panel of fully characterized viral isolates, which could reflect the current dynamic and complex HIV-1 epidemic in China. This panel will be available to support HIV-1 research, assay evaluation, vaccine and drug development.

  16. HIV-1 Reservoir Association with Immune Activation

    Directory of Open Access Journals (Sweden)

    Alejandro Vallejo

    2015-09-01

    Full Text Available In this issue of EBioMedicine, Ruggiero and colleagues describe immune activation biomarkers associated with the size of the HIV reservoir in a carefully designed cross-sectional study. The cohort consists of a homogeneous sample of HIV-1-infected patients with long-term plasma HIV-1 RNA suppression under antiretroviral treatment (ART. It is crucial to explore the potential utility of biomarkers that are easier (less labor intensive, less expensive to measure than integrated HIV DNA load, in order to quickly and accurately quantify cellular reservoirs of HIV.

  17. Hepatitis B Virus Vaccination in HIV-1-Infected Young Adults: A Tool to Reduce the Size of HIV-1 Reservoirs?

    Science.gov (United States)

    Bekele, Yonas; Graham, Rebecka Lantto; Soeria-Atmadja, Sandra; Nasi, Aikaterini; Zazzi, Maurizio; Vicenti, Ilaria; Naver, Lars; Nilsson, Anna; Chiodi, Francesca

    2017-01-01

    During anti-retroviral therapy (ART) HIV-1 persists in cellular reservoirs, mostly represented by CD4+ memory T cells. Several approaches are currently being undertaken to develop a cure for HIV-1 infection through elimination (or reduction) of these reservoirs. Few studies have so far been conducted to assess the possibility of reducing the size of HIV-1 reservoirs through vaccination in virologically controlled HIV-1-infected children. We recently conducted a vaccination study with a combined hepatitis A virus (HAV) and hepatitis B virus (HBV) vaccine in 22 HIV-1-infected children. We assessed the size of the virus reservoir, measured as total HIV-1 DNA copies in blood cells, pre- and postvaccination. In addition, we investigated by immunostaining whether the frequencies of CD4+ and CD8+ T cells and parameters of immune activation and proliferation on these cells were modulated by vaccination. At 1 month from the last vaccination dose, we found that 20 out of 22 children mounted a serological response to HBV; a majority of children had antibodies against HAV at baseline. The number of HIV-1 DNA copies in blood at 1 month postvaccination was reduced in comparison to baseline although this reduction was not statistically significant. A significant reduction of HIV-1 DNA copies in blood following vaccination was found in 12 children. The frequencies of CD4+ (naïve, effector memory) and CD8+ (central memory) T-cell subpopulations changed following vaccinations and a reduction in the activation and proliferation pattern of these cells was also noticed. Multivariate linear regression analysis revealed that the frequency of CD8+ effector memory T cells prior to vaccination was strongly predictive of the reduction of HIV-1 DNA copies in blood following vaccination of the 22 HIV-1-infected children. The results of this study suggest a beneficial effect of vaccination to reduce the size of virus reservoir in HIV-1-infected children receiving ART. A reduced frequency of

  18. Hepatitis B Virus Vaccination in HIV-1-Infected Young Adults: A Tool to Reduce the Size of HIV-1 Reservoirs?

    Directory of Open Access Journals (Sweden)

    Yonas Bekele

    2018-01-01

    Full Text Available During anti-retroviral therapy (ART HIV-1 persists in cellular reservoirs, mostly represented by CD4+ memory T cells. Several approaches are currently being undertaken to develop a cure for HIV-1 infection through elimination (or reduction of these reservoirs. Few studies have so far been conducted to assess the possibility of reducing the size of HIV-1 reservoirs through vaccination in virologically controlled HIV-1-infected children. We recently conducted a vaccination study with a combined hepatitis A virus (HAV and hepatitis B virus (HBV vaccine in 22 HIV-1-infected children. We assessed the size of the virus reservoir, measured as total HIV-1 DNA copies in blood cells, pre- and postvaccination. In addition, we investigated by immunostaining whether the frequencies of CD4+ and CD8+ T cells and parameters of immune activation and proliferation on these cells were modulated by vaccination. At 1 month from the last vaccination dose, we found that 20 out of 22 children mounted a serological response to HBV; a majority of children had antibodies against HAV at baseline. The number of HIV-1 DNA copies in blood at 1 month postvaccination was reduced in comparison to baseline although this reduction was not statistically significant. A significant reduction of HIV-1 DNA copies in blood following vaccination was found in 12 children. The frequencies of CD4+ (naïve, effector memory and CD8+ (central memory T-cell subpopulations changed following vaccinations and a reduction in the activation and proliferation pattern of these cells was also noticed. Multivariate linear regression analysis revealed that the frequency of CD8+ effector memory T cells prior to vaccination was strongly predictive of the reduction of HIV-1 DNA copies in blood following vaccination of the 22 HIV-1-infected children. The results of this study suggest a beneficial effect of vaccination to reduce the size of virus reservoir in HIV-1-infected children receiving ART. A reduced

  19. Hepatitis B Virus Vaccination in HIV-1-Infected Young Adults: A Tool to Reduce the Size of HIV-1 Reservoirs?

    Science.gov (United States)

    Bekele, Yonas; Graham, Rebecka Lantto; Soeria-Atmadja, Sandra; Nasi, Aikaterini; Zazzi, Maurizio; Vicenti, Ilaria; Naver, Lars; Nilsson, Anna; Chiodi, Francesca

    2018-01-01

    During anti-retroviral therapy (ART) HIV-1 persists in cellular reservoirs, mostly represented by CD4+ memory T cells. Several approaches are currently being undertaken to develop a cure for HIV-1 infection through elimination (or reduction) of these reservoirs. Few studies have so far been conducted to assess the possibility of reducing the size of HIV-1 reservoirs through vaccination in virologically controlled HIV-1-infected children. We recently conducted a vaccination study with a combined hepatitis A virus (HAV) and hepatitis B virus (HBV) vaccine in 22 HIV-1-infected children. We assessed the size of the virus reservoir, measured as total HIV-1 DNA copies in blood cells, pre- and postvaccination. In addition, we investigated by immunostaining whether the frequencies of CD4+ and CD8+ T cells and parameters of immune activation and proliferation on these cells were modulated by vaccination. At 1 month from the last vaccination dose, we found that 20 out of 22 children mounted a serological response to HBV; a majority of children had antibodies against HAV at baseline. The number of HIV-1 DNA copies in blood at 1 month postvaccination was reduced in comparison to baseline although this reduction was not statistically significant. A significant reduction of HIV-1 DNA copies in blood following vaccination was found in 12 children. The frequencies of CD4+ (naïve, effector memory) and CD8+ (central memory) T-cell subpopulations changed following vaccinations and a reduction in the activation and proliferation pattern of these cells was also noticed. Multivariate linear regression analysis revealed that the frequency of CD8+ effector memory T cells prior to vaccination was strongly predictive of the reduction of HIV-1 DNA copies in blood following vaccination of the 22 HIV-1-infected children. The results of this study suggest a beneficial effect of vaccination to reduce the size of virus reservoir in HIV-1-infected children receiving ART. A reduced frequency of

  20. Structural and Functional Analysis of HIV-1 Coreceptors: Roles of Charged Residues and Posttranslational Modifications on Coreceptor Activity

    National Research Council Canada - National Science Library

    Chabot, Donald

    2000-01-01

    .... To define these regions we have employed an alanine-scanning mutagenesis strategy of the extracellular domains of CXCR4 coupled with a highly sensitive reporter-gene assay for HIV-1 Env-mediated membrane fusion...

  1. Effect of non-monetary incentives on uptake of couples' counselling and testing among clients attending mobile HIV services in rural Zimbabwe: a cluster-randomised trial.

    Science.gov (United States)

    Sibanda, Euphemia L; Tumushime, Mary; Mufuka, Juliet; Mavedzenge, Sue Napierala; Gudukeya, Stephano; Bautista-Arredondo, Sergio; Hatzold, Karin; Thirumurthy, Harsha; McCoy, Sandra I; Padian, Nancy; Copas, Andrew; Cowan, Frances M

    2017-09-01

    Couples' HIV testing and counselling (CHTC) is associated with greater engagement with HIV prevention and care than individual testing and is cost-effective, but uptake remains suboptimal. Initiating discussion of CHTC might result in distrust between partners. Offering incentives for CHTC could change the focus of the pre-test discussion. We aimed to determine the impact of incentives for CHTC on uptake of couples testing and HIV case diagnosis in rural Zimbabwe. In this cluster-randomised trial, 68 rural communities (the clusters) in four districts receiving mobile HIV testing services were randomly assigned (1:1) to incentives for CHTC or not. Allocation was not masked to participants and researchers. Randomisation was stratified by district and proximity to a health facility. Within each stratum random permutation was done to allocate clusters to the study groups. In intervention communities, residents were informed that couples who tested together could select one of three grocery items worth US$1·50. Standard mobilisation for testing was done in comparison communities. The primary outcome was the proportion of individuals testing with a partner. Analysis was by intention to treat. 3 months after CHTC, couple-testers from four communities per group individually completed a telephone survey to evaluate any social harms resulting from incentives or CHTC. The effect of incentives on CHTC was estimated using logistic regression with random effects adjusting for clustering. The trial was registered with the Pan African Clinical Trial Registry, number PACTR201606001630356. From May 26, 2015, to Jan 29, 2016, of 24 679 participants counselled with data recorded, 14 099 (57·1%) were in the intervention group and 10 580 (42·9%) in the comparison group. 7852 (55·7%) testers in the intervention group versus 1062 (10·0%) in the comparison group tested with a partner (adjusted odds ratio 13·5 [95% CI 10·5-17·4]). Among 427 (83·7%) of 510 eligible

  2. Curcumin derivatives as HIV-1 protease inhibitors

    Energy Technology Data Exchange (ETDEWEB)

    Sui, Z.; Li, J.; Craik, C.S.; Ortiz de Montellano, P.R. [Univ. of California, San Francisco, CA (United States)

    1993-12-31

    Curcumin, a non-toxic natural compound from Curcuma longa, has been found to be an HIV-1 protease inhibitor. Some of its derivatives were synthesized and their inhibitory activity against the HIV-1 protease was tested. Curcumin analogues containing boron enhanced the inhibitory activity. At least of the the synthesized compounds irreversibly inhibits the HIV-1 protease.

  3. HIV-1 transmission networks in high risk fishing communities on the shores of Lake Victoria in Uganda: A phylogenetic and epidemiological approach.

    Directory of Open Access Journals (Sweden)

    Sylvia Kiwuwa-Muyingo

    Full Text Available Fishing communities around Lake Victoria in sub-Saharan Africa have been characterised as a population at high risk of HIV-infection.Using data from a cohort of HIV-positive individuals aged 13-49 years, enrolled from 5 fishing communities on Lake Victoria between 2009-2011, we sought to identify factors contributing to the epidemic and to understand the underlying structure of HIV transmission networks. Clinical and socio-demographic data were combined with HIV-1 phylogenetic analyses. HIV-1 gag-p24 and env-gp-41 sub-genomic fragments were amplified and sequenced from 283 HIV-1-infected participants. Phylogenetic clusters with ≥2 highly related sequences were defined as transmission clusters. Logistic regression models were used to determine factors associated with clustering.Altogether, 24% (n = 67/283 of HIV positive individuals with sequences fell within 34 phylogenetically distinct clusters in at least one gene region (either gag or env. Of these, 83% occurred either within households or within community; 8/34 (24% occurred within household partnerships, and 20/34 (59% within community. 7/12 couples (58% within households clustered together. Individuals in clusters with potential recent transmission (11/34 were more likely to be younger 71% (15/21 versus 46% (21/46 in un-clustered individuals and had recently become resident in the community 67% (14/21 vs 48% (22/46. Four of 11 (36% potential transmission clusters included incident-incident transmissions. Independently, clustering was less likely in HIV subtype D (adjusted Odds Ratio, aOR = 0.51 [95% CI 0.26-1.00] than A and more likely in those living with an HIV-infected individual in the household (aOR = 6.30 [95% CI 3.40-11.68].A large proportion of HIV sexual transmissions occur within house-holds and within communities even in this key mobile population. The findings suggest localized HIV transmissions and hence a potential benefit for the test and treat approach even at a community

  4. HIV-1 gp41 Fusion Intermediate: A Target for HIV Therapeutics

    Directory of Open Access Journals (Sweden)

    Chungen Pan

    2010-02-01

    Full Text Available Human immunodeficiency virus (HIV-1 infection is initiated by the binding of gp120 envelope glyco-protein to its cell receptor (CD4 and a coreceptor (CXCR4 or CCR5, followed by a series of conformational changes in the gp41 transmembrane subunit. These changes include insertion of fusion peptide into the target cell membrane and association of C-heptad repeat (CHR peptide with the N-heptad repeat (NHR trimer, a pre-hairpin fusion intermediate. A stable six-helix bundle core is then formed, bringing the viral envelope and target cell membrane into close proximity for fusion. Peptides derived from the CHR region, such as T20 and C34, inhibit HIV-1 fusion by interacting with the gp41 fusion intermediate. A number of anti-HIV-1 peptides and small molecule compounds targeting the gp41 NHR-trimer have been identified. By combining HIV fusion/entry inhibitors targeting different sites in the gp41 fusion intermediate, a potent synergistic effect takes place, resulting in a potential new therapeutic strategy for the HIV infection/AIDS. Here, we present an overview of the current development of anti-HIV drugs, particularly those targeting the gp41 fusion intermediate.

  5. The dual action of poly(ADP-ribose polymerase -1 (PARP-1 inhibition in HIV-1 infection: HIV-1 LTR inhibition and diminution in Rho GTPase activity

    Directory of Open Access Journals (Sweden)

    Slava eRom

    2015-08-01

    Full Text Available The transcription of HIV-1 (HIV is regulated by complex mechanisms involving various cellular factors and virus-encoded transactivators. Poly(ADP-ribose polymerase 1 (PARP-1 inhibition has emerged recently as a potent anti-inflammatory tool, since PARP-1 is involved in the regulation of some genes through its interaction with various transcription factors. We propose a novel approach to diminish HIV replication via PARP-1 inhibition using human primary monocyte-derived macrophages (MDM as an in vitro model system. PARP-1 inhibitors were able to reduce HIV replication in MDM by 60-80% after 7 days infection. Long Terminal Repeat (LTR acts as a switch in virus replication and can be triggered by several agents such as: Tat, tumor necrosis factor α (TNFα, and phorbol 12-myristate 13-acetate (PMA. Overexpression of Tat in MDM transfected with an LTR reporter plasmid led to a 4.2-fold increase in LTR activation; PARP inhibition resulted in 70% reduction of LTR activity. LTR activity, which increased 3-fold after PMA or TNFα treatment, was reduced by PARP inhibition (by 85-95%. MDM treated with PARP inhibitors showed 90% reduction in NFκB activity (known to mediate PMA- and TNFα-induced HIV LTR activation. Cytoskeleton rearrangements are important in effective HIV-1 infection. PARP inactivation reduced actin cytoskeleton rearrangements by affecting Rho GTPase machinery. These findings suggest that HIV replication in MDM could be suppressed by PARP inhibition via NFκB suppression, diminution of LTR activation and its effects on the cytoskeleton. PARP appears to be essential for HIV replication and its inhibition may provide a potent approach to treatment of HIV infection.

  6. Accumulation of MxB/Mx2-resistant HIV-1 Capsid Variants During Expansion of the HIV-1 Epidemic in Human Populations.

    Science.gov (United States)

    Wei, Wei; Guo, Haoran; Ma, Min; Markham, Richard; Yu, Xiao-Fang

    2016-06-01

    Recent studies have identified human myxovirus resistance protein 2 (MxB or Mx2) as an interferon induced inhibitor of HIV-1 replication. However, whether HIV-1 can overcome MxB restriction without compromise of viral fitness has been undefined. Here, we have discovered that naturally occurring capsid (CA) variants can render HIV-1 resistant to the activity of MxB without losing viral infectivity or the ability to escape from interferon induction. Moreover, these MxB resistant HIV-1 variants do not lose MxB recognition. Surprisingly, MxB resistant CA variants are most commonly found in the Clade C HIV-1 that is the most rapidly expanding Clade throughout the world. Accumulation of MxB resistant mutations is also observed during HIV-1 spreading in human populations. These findings support a potential role for MxB as a selective force during HIV-1 transmission and evolution. Copyright © 2016. Published by Elsevier B.V.

  7. The HIV-1 Rev/RRE system is required for HIV-1 5' UTR cis elements to augment encapsidation of heterologous RNA into HIV-1 viral particles

    Directory of Open Access Journals (Sweden)

    Ma Hong

    2011-06-01

    Full Text Available Abstract Background The process of HIV-1 genomic RNA (gRNA encapsidation is governed by a number of viral encoded components, most notably the Gag protein and gRNA cis elements in the canonical packaging signal (ψ. Also implicated in encapsidation are cis determinants in the R, U5, and PBS (primer binding site from the 5' untranslated region (UTR. Although conventionally associated with nuclear export of HIV-1 RNA, there is a burgeoning role for the Rev/RRE in the encapsidation process. Pleiotropic effects exhibited by these cis and trans viral components may confound the ability to examine their independent, and combined, impact on encapsidation of RNA into HIV-1 viral particles in their innate viral context. We systematically reconstructed the HIV-1 packaging system in the context of a heterologous murine leukemia virus (MLV vector RNA to elucidate a mechanism in which the Rev/RRE system is central to achieving efficient and specific encapsidation into HIV-1 viral particles. Results We show for the first time that the Rev/RRE system can augment RNA encapsidation independent of all cis elements from the 5' UTR (R, U5, PBS, and ψ. Incorporation of all the 5' UTR cis elements did not enhance RNA encapsidation in the absence of the Rev/RRE system. In fact, we demonstrate that the Rev/RRE system is required for specific and efficient encapsidation commonly associated with the canonical packaging signal. The mechanism of Rev/RRE-mediated encapsidation is not a general phenomenon, since the combination of the Rev/RRE system and 5' UTR cis elements did not enhance encapsidation into MLV-derived viral particles. Lastly, we show that heterologous MLV RNAs conform to transduction properties commonly associated with HIV-1 viral particles, including in vivo transduction of non-dividing cells (i.e. mouse neurons; however, the cDNA forms are episomes predominantly in the 1-LTR circle form. Conclusions Premised on encapsidation of a heterologous RNA into

  8. [HIV-1 genetic variability in non Spaniard infected children].

    Science.gov (United States)

    Piñeiro Pérez, R; Mellado Peña, M J; Holguín, A; Cilleruelo, M J; García Hortelano, M; Villota, J; Martín Fontelos, P

    2009-01-01

    The prevalence of HIV-1 non-B subtypes (HIV-NBS) is increasing in Europe, because of emigration from countries where genetic variants are endemic. Although HIV-NBS could have a different clinical evolution and could respond differently to antiretrovirals (AR) than B-subtypes, these variant's response remain undocumented. To identify HIV-1 genetic variants and to determine clinical evolution in a non-Spaniard children infected with HIV-1. Children with HIV-1 infection from endemic countries were tested for HIV-1 subtypes between 1-1-1988 and 31-12-2006. Twelve children less than 18 years old and born abroad were selected. HIV-NBS were isolated in 5 children (42%): CRF2_AG recombinant in 3 cases (Equatorial Guinea), Subtype C in one (Equatorial Guinea) and CRF13_cpx in last one (India). Because of the increasing frequency of patients with HIV-NBS and their unknown long-term evolution, all children from endemic countries should be tested for HIV subtypes. We believe new studies with more patients during longer times could reveal differences in these patient's clinical, immunological and virological evolution.

  9. Gendered power dynamics and women’s negotiation of family planning in a high HIV prevalence setting: A qualitative study of couples in western Kenya

    Science.gov (United States)

    Harrington, Elizabeth K.; Dworkin, Shari; Withers, Mellissa; Onono, Maricianah; Kwena, Zachary; Newmann, Sara J.

    2017-01-01

    In sub-Saharan Africa, high burdens of HIV and unmet need for contraception often coexist. Research emphasises the need to engage men and couples in reproductive health, yet couples’ negotiations around fertility and family planning in the context of HIV have been sparsely studied. This study examined the gendered power dynamics that frame women’s and couples’ negotiations of contraceptive use in western Kenya. We conducted 76 in-depth interviews with 38 couples, of whom 22 couples were concordant HIV-positive. Qualitative data were analysed using a grounded theory approach. Direct communication around contraception with men was often challenging due to perceived or expressed male resistance. A substantial minority of women avoided male reproductive decision-making authority through covert contraceptive use, with concern for severe consequences when contraceptive use was discovered. Many men assumed that family planning use signified female promiscuity and that infidelity motivated covert use. Men were more willing to use condoms to avoid HIV re-infection or at the recommendation of HIV care providers, which allowed some women leverage to insist on condom use. Our findings highlight the tension between male-dominated reproductive decision-making and women’s agency and point to the need for gender transformative approaches seeking to challenge masculinities that negatively impact health. PMID:26503879

  10. Novel Synthesis and Anti-HIV-1 Activity of 2-Arylthio-6-benzyl-2,3-dihydro-1H-pyrimidin-4-ones (Aryl S-DABOs)

    DEFF Research Database (Denmark)

    Aly, Youssef L.; Pedersen, Erik Bjerreg.; La Colla, Paolo

    2007-01-01

    The synthesis and the anti-HIV-1 activity of a series of 2-arylthio-6-benzyl-2,3-dihydro-1H-pyrimidin-4-ones (aryl S-DABOs) are reported. These compounds were synthesized via a coupling reaction of the corresponding 6-benzyl-2-thiouracils with aryl iodides in the presence of neocuproine hydrate...

  11. Comparison of the RealTime HIV-1, COBAS TaqMan 48 v1.0, Easy Q v1.2, and Versant v3.0 assays for Determination of HIV-1 Viral Loads in a Cohort of Canadian Patients with Diverse HIV Subtype Infections▿

    OpenAIRE

    Church, Deirdre; Gregson, Daniel; Lloyd, Tracie; Klein, Marina; Beckthold, Brenda; Laupland, Kevin; Gill, M. John

    2010-01-01

    HIV clinics in Canada provide care to an increasing number of patients born outside of Canada with HIV-1 non-B subtype infections. Because the Easy Q HIV-1 v1.2 assay (EQ; bioMérieux) failed to detect some non-B subtype infections, a multiassay HIV-1 viral load (VL) study was conducted with patients with diverse HIV subtype infections. Patients were enrolled from the Southern Alberta HIV Clinic (SAC), Calgary, Alberta, Canada (n = 349) and the McGill HIV Clinic (MHC), Montreal, Quebec, Canada...

  12. HIV-1 viral load measurement in venous blood and fingerprick blood using Abbott RealTime HIV-1 DBS assay.

    Science.gov (United States)

    Tang, Ning; Pahalawatta, Vihanga; Frank, Andrea; Bagley, Zowie; Viana, Raquel; Lampinen, John; Leckie, Gregor; Huang, Shihai; Abravaya, Klara; Wallis, Carole L

    2017-07-01

    HIV RNA suppression is a key indicator for monitoring success of antiretroviral therapy. From a logistical perspective, viral load (VL) testing using Dried Blood Spots (DBS) is a promising alternative to plasma based VL testing in resource-limited settings. To evaluate the analytical and clinical performance of the Abbott RealTime HIV-1 assay using a fully automated one-spot DBS sample protocol. Limit of detection (LOD), linearity, lower limit of quantitation (LLQ), upper limit of quantitation (ULQ), and precision were determined using serial dilutions of HIV-1 Virology Quality Assurance stock (VQA Rush University), or HIV-1-containing armored RNA, made in venous blood. To evaluate correlation, bias, and agreement, 497 HIV-1 positive adult clinical samples were collected from Ivory Coast, Uganda and South Africa. For each HIV-1 participant, DBS-fingerprick, DBS-venous and plasma sample results were compared. Correlation and bias values were obtained. The sensitivity and specificity were analyzed at a threshold of 1000 HIV-1 copies/mL generated using the standard plasma protocol. The Abbott HIV-1 DBS protocol had an LOD of 839 copies/mL, a linear range from 500 to 1×10 7 copies/mL, an LLQ of 839 copies/mL, a ULQ of 1×10 7 copies/mL, and an inter-assay SD of ≤0.30 log copies/mL for all tested levels within this range. With clinical samples, the correlation coefficient (r value) was 0.896 between DBS-fingerprick and plasma and 0.901 between DBS-venous and plasma, and the bias was -0.07 log copies/mL between DBS-fingerprick and plasma and -0.02 log copies/mL between DBS-venous and plasma. The sensitivity of DBS-fingerprick and DBS-venous was 93%, while the specificity of both DBS methods was 95%. The results demonstrated that the Abbott RealTime HIV-1 assay with DBS sample protocol is highly sensitive, specific and precise across a wide dynamic range and correlates well with plasma values. The Abbott RealTime HIV-1 assay with DBS sample protocol provides an

  13. Dose-Response Associations Between Number and Frequency of Substance Use and High-Risk Sexual Behaviors Among HIV-Negative Substance-Using Men Who Have Sex With Men (SUMSM) in San Francisco

    Science.gov (United States)

    Santos, Glenn-Milo; Coffin, Phillip O.; Das, Moupali; Matheson, Tim; DeMicco, Erin; Raiford, Jerris L.; Vittinghoff, Eric; Dilley, James W.; Colfax, Grant; Herbst, Jeffrey H.

    2015-01-01

    We evaluated the relationship between frequency and number of substances used and HIV risk [ie, serodiscordant unprotected anal intercourse (SDUAI)] among 3173 HIV-negative substance-using MSM. Compared with nonusers, the adjusted odds ratio (AOR) for SDUAI among episodic and at least weekly users, respectively, was 3.31 [95% confidence interval (CI), 2.55 to 4.28] and 5.46 (95% CI, 3.80 to 7.84) for methamphetamine, 1.86 (95% CI, 1.51 to 2.29) and 3.13 (95% CI, 2.12 to 4.63) for cocaine, and 2.08 (95% CI, 1.68 to 2.56) and 2.54 (95% CI, 1.85 to 3.48) for poppers. Heavy alcohol drinkers reported more SDUAI than moderate drinkers [AOR, 1.90 (95% CI, 1.43 to 2.51)]. Compared with nonusers, AORs for using 1, 2, and ≥3 substances were 16.81 (95% CI, 12.25 to 23.08), 27.31 (95% CI, 18.93 to 39.39), and 46.38 (95% CI, 30.65 to 70.19), respectively. High-risk sexual behaviors were strongly associated with frequency and number of substances used. PMID:23572012

  14. Community study of the relative impact of HIV-1 and HIV-2 on intrathoracic tuberculosis

    DEFF Research Database (Denmark)

    Seng, R; Gustafson, P; Gomes, VF

    2002-01-01

    BACKGROUND: HIV-1 infection is associated with an increased incidence of and mortality from tuberculosis. Few community studies have examined the effect of HIV-2 on tuberculosis. METHODS: We investigated the association between HIV-1, HIV-2 and active tuberculosis in four districts (population 42...

  15. Structural Study of a New HIV-1 Entry Inhibitor and Interaction with the HIV-1 Fusion Peptide in Dodecylphosphocholine Micelles.

    Science.gov (United States)

    Pérez, Yolanda; Gómara, Maria José; Yuste, Eloísa; Gómez-Gutierrez, Patricia; Pérez, Juan Jesús; Haro, Isabel

    2017-08-25

    Previous studies support the hypothesis that the envelope GB virus C (GBV-C) E1 protein interferes the HIV-1 entry and that a peptide, derived from the region 139-156 of this protein, has been defined as a novel HIV-1 entry inhibitor. In this work, we firstly focus on the characterization of the structural features of this peptide, which are determinant for its anti-HIV-1 activity and secondly, on the study of its interaction with the proposed viral target (i.e., the HIV-1 fusion peptide). We report the structure of the peptide determined by NMR spectroscopy in dodecylphosphocholine (DPC) micelles solved by using restrained molecular dynamics calculations. The acquisition of different NMR experiments in DPC micelles (i.e., peptide-peptide titration, diffusion NMR spectroscopy, and addition of paramagnetic relaxation agents) allows a proposal of an inhibition mechanism. We conclude that a 18-mer peptide from the non-pathogenic E1 GBV-C protein, with a helix-turn-helix structure inhibits HIV-1 by binding to the HIV-1 fusion peptide at the membrane level, thereby interfering with those domains in the HIV-1, which are critical for stabilizing the six-helix bundle formation in a membranous environment. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  16. Correlation between HIV-1 genotype and clinical progression in HIV/AIDS patients in Surabaya, Indonesia

    Science.gov (United States)

    Rachman, B. E.; Khairunisa, S. Q.; Witaningrum, A. M.; Yunifiar, M. Q.; Nasronudin

    2018-03-01

    Several factors such as host and viral factors can affect the progression of HIV/AIDS. This study aims to identify the correlation viral factors, especially the HIV-1 subtype with HIV/AIDS progression. Inpatient HIV/AIDS during the period March to September 2017 and willing to participate are included in the study. Historical data of disease and treatment was taken by medical record. Blood samples were amplified, sequenced and undergone phylogenetic analysis. Linear regression analysis was used to estimate beta coefficient (β) and 95%CI of HIV/AIDS progression (measured by the CD4 change rate, ΔCD4 cell count/time span in months).This study has 17 samples. The HIV-1 subtype was dominated by CRF01_AE (81.8%) followed by subtype B (18.2%). There was significant correlation between subtype HIV-1 (p = 0.04) and body mass index (p = 0.038) with HIV/AIDS clinical stage. Many factors were assumed to be correlated with increased rate of CD4, but we only subtype HIV-1 had a significant correlation (p = 0.024) with it. From multivariate analysis, we also found that subtype HIV-1 had a significant correlation (β = 0.788, 95%CI: 17.5-38.6, p = 0.004).

  17. Characterization of natural polymorphic sites of the HIV-1 integrase before the introduction of HIV-1 integrase inhibitors in Germany

    Science.gov (United States)

    Meixenberger, Karolin; Pouran Yousef, Kaveh; Somogyi, Sybille; Fiedler, Stefan; Bartmeyer, Barbara; von Kleist, Max; Kücherer, Claudia

    2014-01-01

    Introduction The aim of our study was to analyze the occurrence and evolution of HIV-1 integrase polymorphisms during the HIV-1 epidemic in Germany prior to the introduction of the first integrase inhibitor raltegravir in 2007. Materials and Methods Plasma samples from drug-naïve HIV-1 infected individuals newly diagnosed between 1986 and 2006 were used to determine PCR-based population sequences of the HIV-1 integrase (amino acids 1–278). The HIV-1 subtype was determined using the REGA HIV-1 subtyping tool. We calculated the frequency of amino acids at each position of the HIV-1 integrase in 337 subtype B strains for the time periods 1986–1989, 1991–1994, 1995–1998, 1999–2002, and 2003–2006. Positions were defined as polymorphic if amino acid variation was >1% in any period. Logistic regression was used to identify trends in amino acid variation over time. Resistance-associated mutations were identified according to the IAS 2013 list and the HIVdb, ANRS and GRADE algorithms. Results Overall, 56.8% (158/278) amino acid positions were polymorphic and 15.8% (25/158) of these positions exhibited a significant trend in amino acid variation over time. Proportionately, most polymorphic positions (63.3%, 31/49) were detected in the N-terminal zinc finger domain of the HIV-1 integrase. Motifs and residues essential for HIV-1 integrase activity were little polymorphic, but within the minimal non-specific DNA binding region I220-D270 up to 18.1% amino acid variation was noticed, including four positions with significant amino acid variation over time (S230, D232, D256, A265). No major resistance mutations were identified, and minor resistance mutations were rarely observed without trend over time. E157Q considered by HIVdb, ANRS, and GRADE algorithms was the most frequent resistance-associated polymorphism with an overall prevalence of 2.4%. Conclusions Detailed knowledge of the evolutionary variation of HIV-1 integrase polymorphisms is important to understand

  18. Anal intercourse without condoms among HIV-positive men who have sex with men recruited from a sexual networking web site, United States.

    Science.gov (United States)

    Margolis, Andrew D; Joseph, Heather; Hirshfield, Sabina; Chiasson, Mary Ann; Belcher, Lisa; Purcell, David W

    2014-12-01

    The changing landscape of HIV prevention in the United States underscores the need to improve our ability to efficiently reach HIV-positive men who have sex with men (MSM) who engage in behaviors that could transmit HIV. We examined the prevalence of anal intercourse (AI) without condoms with HIV-negative or unknown serostatus partners ("at-risk partners") among 1319 HIV-positive adult male members of a sexual networking Web site for MSM. Sexual behaviors and substance use were measured over a 60-day recall period. Logistic regression was used to identify correlates of insertive and receptive AI without condoms with at-risk partners. Approximately 25% of the men had been diagnosed as having HIV 12 months or less before study enrollment. Overall, 32% of men engaged in AI without condoms with at-risk partners. Multiple logistic regression identified behavioral predictors of insertive AI without condoms with at-risk partners, including HIV diagnosis within the last 12 months, sex with multiple male partners, substance use in conjunction with sex, and use of phosphodiesterase type 5 inhibitors. Receptive AI without condoms with at-risk partners was associated with younger age (19-24 years), residing outside metropolitan cities, substance use in conjunction with sex, and having multiple male partners. High levels of sexual risk were found among these MSM. Increased Internet-based HIV prevention marketing efforts and prevention strategies should be considered to efficiently reach HIV-positive MSM who engage in serodiscordant AI without condoms.

  19. Cyclophilin B enhances HIV-1 infection.

    Science.gov (United States)

    DeBoer, Jason; Madson, Christian J; Belshan, Michael

    2016-02-01

    Cyclophilin B (CypB) is a member of the immunophilin family and intracellular chaperone. It predominantly localizes to the ER, but also contains a nuclear localization signal and is secreted from cells. CypB has been shown to interact with the Gag protein of human immunodeficiency type 1 (HIV-1). Several proteomic and genetic studies identified it as a potential factor involved in HIV replication. Herein, we show that over-expression of CypB enhances HIV infection by increasing nuclear import of viral DNA. This enhancement was unaffected by cyclosporine treatment and requires the N-terminus of the protein. The N-terminus contains an ER leader sequence, putative nuclear localization signal, and is required for secretion. Deletion of the N-terminus resulted in mislocalization from the ER and suppression of HIV infection. Passive transfer experiments showed that secreted CypB did not impact HIV infection. Combined, these experiments show that intracellular CypB modulates a pathway of HIV nuclear import. Copyright © 2015 Elsevier Inc. All rights reserved.

  20. Minimal residual HIV viremia: verification of the Abbott Real-Time HIV-1 assay sensitivity

    Directory of Open Access Journals (Sweden)

    Alessandra Amendola

    2010-06-01

    Full Text Available Introduction: In the HIV-1 infection, the increase in number of CD4 T lymphocytes and the viral load decline are the main indicators of the effectiveness of antiretroviral therapy. On average, 85% of patients receiving effective treatment has a persistent suppression of plasma viral load below the detection limit (<50 copies/mL of clinically used viral load assays, regardless of treatment regimen in use. It is known, however, that, even when viremia is reduced below the sensitivity limit of current diagnostic assays, the virus persists in “reservoirs” and traces of free virions can be detected in plasma.There is a considerable interest to investigate the clinical significance of residual viremia. Advances in molecular diagnostics allows nowadays to couple a wide dynamic range to a high sensitivity.The Abbott Real-time HIV-1 test is linear from 40 to 107 copies/mL and provides, below 40 copies/mL, additional information such as “<40cp/mL, target detected” or “target not detected”. The HIV-1 detection is verified by the max-Ratio algorithm software.We assessed the test sensitivity when the qualitative response is considered as well. Methods: A ‘probit’ analysis was performed using dilutions of the HIV-1 RNA Working Reagent 1 for NAT assays (NIBSC code: 99/634, defined in IU/mL and different from that used by the manufacturer (VQA,Virology Quality Assurance Laboratory of the AIDS Clinical Trial Group for standardization and definition of performances.The sample input volume (0.6 mL was the same used in clinical routine. A total of 196 replicates at concentrations decreasing from 120 to 5 copies/mL, in three different sessions, have been tested.The ‘probit’ analysis (binomial dose-response model, 95% “hit-rate” has been carried out on the SAS 9.1.3 software package. Results: The sensitivity of the “<40cp/mL, target detected” response was equal to 28,76 copies/mL, with 95% confidence limits between 22,19 and 52,27 copies

  1. Field evaluation of an open and polyvalent universal HIV-1/SIVcpz/SIVgor quantitative RT-PCR assay for HIV-1 viral load monitoring in comparison to Abbott RealTime HIV-1 in Cameroon.

    Science.gov (United States)

    Guichet, Emilande; Aghokeng, Avelin; Eymard-Duvernay, Sabrina; Vidal, Nicole; Ayouba, Ahidjo; Mpoudi Ngole, Eitel; Delaporte, Eric; Ciaffi, Laura; Peeters, Martine

    2016-11-01

    With the increasing demand of HIV viral load (VL) tests in resource-limited countries (RLCs) there is a need for assays at affordable cost and able to quantify all known HIV-1 variants. VLs obtained with a recently developed open and polyvalent universal HIV-1/SIVcpz/SIVgor RT-qPCR were compared to Abbott RealTime HIV-1 assay in Cameroon. On 474 plasma samples, characterized by a wide range of VLs and a broad HIV-1 group M genetic diversity, 97.5% concordance was observed when using the lower detection limit of each assay. When using the threshold of 3.00 log 10 copies/mL, according to WHO guidelines to define virological failure (VF) in RLCs, the concordance was 94.7%, 360/474 versus 339/474 patients were identified with VF with the new assay and Abbott RealTime HIV-1, respectively. Higher VLs were measured with the new assay, +0.47 log 10 copies/mL (95% CI; 0.42-0.52) as shown with Bland-Altman analysis. Eleven samples from patients on VF with drug resistance were not detected by Abbott RealTime HIV-1 versus two only with the new assay. Overall, our study showed that the new assay can be easily implemented in a laboratory in RLCs with VL experience and showed good performance on a wide diversity of HIV-1 group M variants. Copyright © 2016 Elsevier B.V. All rights reserved.

  2. The global transmission network of HIV-1.

    Science.gov (United States)

    Wertheim, Joel O; Leigh Brown, Andrew J; Hepler, N Lance; Mehta, Sanjay R; Richman, Douglas D; Smith, Davey M; Kosakovsky Pond, Sergei L

    2014-01-15

    Human immunodeficiency virus type 1 (HIV-1) is pandemic, but its contemporary global transmission network has not been characterized. A better understanding of the properties and dynamics of this network is essential for surveillance, prevention, and eventual eradication of HIV. Here, we apply a simple and computationally efficient network-based approach to all publicly available HIV polymerase sequences in the global database, revealing a contemporary picture of the spread of HIV-1 within and between countries. This approach automatically recovered well-characterized transmission clusters and extended other clusters thought to be contained within a single country across international borders. In addition, previously undescribed transmission clusters were discovered. Together, these clusters represent all known modes of HIV transmission. The extent of international linkage revealed by our comprehensive approach demonstrates the need to consider the global diversity of HIV, even when describing local epidemics. Finally, the speed of this method allows for near-real-time surveillance of the pandemic's progression.

  3. Evaluation of four rapid tests for diagnosis and differentiation of HIV-1 and HIV-2 infections in Guinea-Conakry, West Africa.

    Science.gov (United States)

    Chaillet, Pascale; Tayler-Smith, Katie; Zachariah, Rony; Duclos, Nanfack; Moctar, Diallo; Beelaert, Greet; Fransen, Katrien

    2010-09-01

    With both HIV-1 and HV-2 prevalent in Guinea-Conakry, accurate diagnosis and differentiation is crucial for treatment purposes. Thus, four rapid HIV tests were evaluated for their HIV-1 and HIV-2 diagnostic and discriminative capacity for use in Guinea-Conakry. These included SD Bioline HIV 1/2 3.0 (Standard Diagnostics Inc.), Genie II HIV1/HIV2 (Bio-Rad), First Response HIV Card Test 1-2.0 (PMC Medical) and Immunoflow HIV1-HIV2 (Core Diagnostics). Results were compared with gold standard tests (INNO-LIA HIV-I/II Score) and NEW LAV BLOT II (Bio-Rad). Four hundred and forty three sequential stored HIV-positive serum samples, of known HIV-type, were evaluated. Genie II HIV1/HIV2, Immunoflow HIV1-HIV2 and SD Bioline HIV 1/2 3.0 had 100% sensitivity (95% CI, 98.9-100%) while for First Response HIV Card Test 1-2.0 this was 99.5% (95% CI, 98.2%-99.9%). In terms of discriminatory capacity, Genie II HIV1/HIV2 identified 382/ 384(99.5%) HIV-1 samples, 49/ 52(95%) HIV-2 and 7/7(100%) HIV-positive untypable samples. Immunoflow HIV1-HIV2 identified 99% HIV-1, 67% HIV-2 and all HIV-positive untypable samples. First Response HIV Card Test 1-2.0 identified 94% HIV-1, 64% HIV-2 and 57% HIV-positive untypable samples. SD-Bioline HIV 1/2 3.0 was the worst overall performer identifying 65% HIV-1, 69% HIV-2 and all HIV-positive untypable samples. The use of SD Bioline HIV 1/2 3.0 (the current standard in Guinea-Conakry) as a discriminatory HIV test is poor and may be best replaced by Immunoflow HIV1-HIV2. Copyright 2010 Royal Society of Tropical Medicine and Hygiene. Published by Elsevier Ltd. All rights reserved.

  4. HIV-1 proteins dysregulate motivational processes and dopamine circuitry.

    Science.gov (United States)

    Bertrand, Sarah J; Mactutus, Charles F; Harrod, Steven B; Moran, Landhing M; Booze, Rosemarie M

    2018-05-18

    Motivational alterations, such as apathy, in HIV-1+ individuals are associated with decreased performance on tasks involving frontal-subcortical circuitry. We used the HIV-1 transgenic (Tg) rat to assess effect of long-term HIV-1 protein exposure on motivated behavior using sucrose (1-30%, w/v) and cocaine (0.01-1.0 mg/kg/infusion) maintained responding with fixed-ratio (FR) and progressive-ratio (PR) schedules of reinforcement. For sucrose-reinforced responding, HIV-1 Tg rats displayed no change in EC 50 relative to controls, suggesting no change in sucrose reinforcement but had a downward shifted concentration-response curves, suggesting a decrease in response vigor. Cocaine-maintained responding was attenuated in HIV-1 Tg rats (FR1 0.33 mg/kg/infusion and PR 1.0 mg/kg/infusion). Dose-response tests (PR) revealed that HIV-1 Tg animals responded significantly less than F344 control rats and failed to earn significantly more infusions of cocaine as the unit dose increased. When choosing between cocaine and sucrose, control rats initially chose sucrose but with time shifted to a cocaine preference. In contrast, HIV-1 disrupted choice behaviors. DAT function was altered in the striatum of HIV-1 Tg rats; however, prior cocaine self-administration produced a unique effect on dopamine homeostasis in the HIV-1 Tg striatum. These findings of altered goal directed behaviors may determine neurobiological mechanisms of apathy in HIV-1+ patients.

  5. Profile of HIV-1 RNA viral load among HIV-TB co-infected patients in ...

    African Journals Online (AJOL)

    Profile of HIV-1 RNA viral load among HIV-TB co-infected patients in a tertiary health facility in Maiduguri, Northeastern Nigeria. ... This study aims to estimate the HIV-1 RNA viral load and impact of anti TB therapy (ATT) ... HOW TO USE AJOL.

  6. Sieve analysis in HIV-1 vaccine efficacy trials.

    Science.gov (United States)

    Edlefsen, Paul T; Gilbert, Peter B; Rolland, Morgane

    2013-09-01

    The genetic characterization of HIV-1 breakthrough infections in vaccine and placebo recipients offers new ways to assess vaccine efficacy trials. Statistical and sequence analysis methods provide opportunities to mine the mechanisms behind the effect of an HIV vaccine. The release of results from two HIV-1 vaccine efficacy trials, Step/HVTN-502 (HIV Vaccine Trials Network-502) and RV144, led to numerous studies in the last 5 years, including efforts to sequence HIV-1 breakthrough infections and compare viral characteristics between the vaccine and placebo groups. Novel genetic and statistical analysis methods uncovered features that distinguished founder viruses isolated from vaccinees from those isolated from placebo recipients, and identified HIV-1 genetic targets of vaccine-induced immune responses. Studies of HIV-1 breakthrough infections in vaccine efficacy trials can provide an independent confirmation to correlates of risk studies, as they take advantage of vaccine/placebo comparisons, whereas correlates of risk analyses are limited to vaccine recipients. Through the identification of viral determinants impacted by vaccine-mediated host immune responses, sieve analyses can shed light on potential mechanisms of vaccine protection.

  7. Constitutively Active MAVS Inhibits HIV-1 Replication via Type I Interferon Secretion and Induction of HIV-1 Restriction Factors.

    Directory of Open Access Journals (Sweden)

    Sachin Gupta

    Full Text Available Type I interferon is known to inhibit HIV-1 replication through the induction of interferon stimulated genes (ISG, including a number of HIV-1 restriction factors. To better understand interferon-mediated HIV-1 restriction, we constructed a constitutively active form of the RIG-I adapter protein MAVS. Constitutive MAVS was generated by fusion of full length MAVS to a truncated form of the Epstein Barr virus protein LMP1 (ΔLMP1. Supernatant from ΔLMP1-MAVS-transfected 293T cells contained high levels of type I interferons and inhibited HIV replication in both TZM-bl and primary human CD4+ T cells. Supernatant from ΔLMP1-MAVS-transfected 293T cells also inhibited replication of VSV-G pseudotyped single cycle SIV in TZM-bl cells, suggesting restriction was post-entry and common to both HIV and SIV. Gene array analysis of ΔLMP1-MAVS-transfected 293T cells and trans-activated CD4+ T cells showed significant upregulation of ISG, including previously characterized HIV restriction factors Viperin, Tetherin, MxB, and ISG56. Interferon blockade studies implicated interferon-beta in this response. In addition to direct viral inhibition, ΔLMP1-MAVS markedly enhanced secretion of IFN-β and IL-12p70 by dendritic cells and the activation and maturation of dendritic cells. Based on this immunostimulatory activity, an adenoviral vector (Ad5 expressing ΔLMP1-MAVS was tested as a molecular adjuvant in an HIV vaccine mouse model. Ad5-Gag antigen combined with Ad5-ΔLMP1-MAVS enhanced control of vaccinia-gag replication in a mouse challenge model, with 4/5 animals showing undetectable virus following challenge. Overall, ΔLMP1-MAVS is a promising reagent to inhibit HIV-1 replication in infected tissues and enhance vaccine-mediated immune responses, while avoiding toxicity associated with systemic type I interferon administration.

  8. Frequency and site mapping of HIV-1/SIVcpz, HIV- 2/SIVsmm and ...

    African Journals Online (AJOL)

    out to analyze the effects of various restriction enzymes on the HIV genome. A computer simulated model using Web cutter Version 2.0, and cytogenetic analysis. 339 restriction enzymes from Promega database, 10 HIV-1/SIVcpz genes, 10 HIV-2/SIVsmm genes and 10 other SIV genes. Gene sequences were fed into Web ...

  9. The C-terminal sequence of IFITM1 regulates its anti-HIV-1 activity.

    Directory of Open Access Journals (Sweden)

    Rui Jia

    Full Text Available The interferon-inducible transmembrane (IFITM proteins inhibit a wide range of viruses. We previously reported the inhibition of human immunodeficiency virus type 1 (HIV-1 strain BH10 by human IFITM1, 2 and 3. It is unknown whether other HIV-1 strains are similarly inhibited by IFITMs and whether there exists viral countermeasure to overcome IFITM inhibition. We report here that the HIV-1 NL4-3 strain (HIV-1NL4-3 is not restricted by IFITM1 and its viral envelope glycoprotein is partly responsible for this insensitivity. However, HIV-1NL4-3 is profoundly inhibited by an IFITM1 mutant, known as Δ(117-125, which is deleted of 9 amino acids at the C-terminus. In contrast to the wild type IFITM1, which does not affect HIV-1 entry, the Δ(117-125 mutant diminishes HIV-1NL4-3 entry by 3-fold. This inhibition correlates with the predominant localization of Δ(117-125 to the plasma membrane where HIV-1 entry occurs. In spite of strong conservation of IFITM1 among most species, mouse IFITM1 is 19 amino acids shorter at its C-terminus as compared to human IFITM1 and, like the human IFITM1 mutant Δ(117-125, mouse IFITM1 also inhibits HIV-1 entry. This is the first report illustrating the role of viral envelope protein in overcoming IFITM1 restriction. The results also demonstrate the importance of the C-terminal region of IFITM1 in modulating the antiviral function through controlling protein subcellular localization.

  10. Dual-mixed HIV-1 coreceptor tropism and HIV-associated neurocognitive deficits.

    Science.gov (United States)

    Morris, Sheldon R; Woods, Steven Paul; Deutsch, Reena; Little, Susan J; Wagner, Gabriel; Morgan, Erin E; Heaton, Robert K; Letendre, Scott L; Grant, Igor; Smith, Davey M

    2013-10-01

    HIV coreceptor usage of CXCR4 (X4) is associated with decreased CD4+ T-cell counts and accelerated disease progression, but the role of X4 tropism in HIV-associated neurocognitive disorders (HAND) has not previously been described. This longitudinal study evaluated data on 197 visits from 72 recently HIV-infected persons who had undergone up to four sequential neurocognitive assessments over a median of 160 days (IQR, 138–192). Phenotypic tropism testing (Trofile ES, Monogram, Biosciences) was performed on stored blood samples. Multivariable mixed model repeated measures regression was used to determine the association between HAND and dual-mixed (DM) viral tropism, estimated duration of infection (EDI), HIV RNA, CD4 count, and problematic methamphetamine use. Six subjects (8.3 %) had DM at their first neurocognitive assessment and four converted to DM in subsequent sampling (for total of 10 DM) at a median EDI of 10.1 months (IQR, 7.2–12.2). There were 44 (61.1 %) subjects who demonstrated HAND on at least one study visit. HAND was associated with DM tropism (odds ratio, 4.4; 95 % CI, 0.9–20.5) and shorter EDI (odds ratio 1.1 per month earlier; 95 % CI, 1.0–1.2). This study found that recency of HIV-1 infection and the development of DM tropism may be associated with HAND in the relatively early stage of infection. Together, these data suggest that viral interaction with cellular receptors may play an important role in the early manifestation of HAND.

  11. HIV/HTLV-1 co-infection

    African Journals Online (AJOL)

    result of a lymphoproliferative disorder. In the context of HIV co-infection, lympho- cytosis has been described during early sero- conversion associated with CMV, as well as in HIV/HTLV-1 co-infection where CD4+ lymphocytosis can be caused by both a reactive or clonal expansion. Consequently, patients with untreated ...

  12. Correlates of HIV-1 genital shedding in Tanzanian women.

    Directory of Open Access Journals (Sweden)

    Clare Tanton

    2011-03-01

    Full Text Available Understanding the correlates of HIV shedding is important to inform strategies to reduce HIV infectiousness. We examined correlates of genital HIV-1 RNA in women who were seropositive for both herpes simplex virus (HSV-2 and HIV-1 and who were enrolled in a randomised controlled trial of HSV suppressive therapy (aciclovir 400 mg b.i.d vs. placebo in Tanzania.Samples, including a cervico-vaginal lavage, were collected and tested for genital HIV-1 and HSV and reproductive tract infections (RTIs at randomisation and 6, 12 and 24 months follow-up. Data from all women at randomisation and women in the placebo arm during follow-up were analysed using generalised estimating equations to determine the correlates of cervico-vaginal HIV-1 RNA detection and load.Cervico-vaginal HIV-1 RNA was detected at 52.0% of 971 visits among 482 women, and was independently associated with plasma viral load, presence of genital ulcers, pregnancy, bloody cervical or vaginal discharge, abnormal vaginal discharge, cervical ectopy, Neisseria gonorrhoeae, Chlamydia trachomatis, Trichomonas vaginalis, an intermediate bacterial vaginosis score and HSV DNA detection. Similar factors were associated with genital HIV-1 RNA load.RTIs were associated with increased presence and quantity of genital HIV-1 RNA in this population. These results highlight the importance of integrating effective RTI treatment into HIV care services.

  13. Frequent intra-subtype recombination among HIV-1 circulating in Tanzania.

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    Ireen E Kiwelu

    Full Text Available The study estimated the prevalence of HIV-1 intra-subtype recombinant variants among female bar and hotel workers in Tanzania. While intra-subtype recombination occurs in HIV-1, it is generally underestimated. HIV-1 env gp120 V1-C5 quasispecies from 45 subjects were generated by single-genome amplification and sequencing (median (IQR of 38 (28-50 sequences per subject. Recombination analysis was performed using seven methods implemented within the recombination detection program version 3, RDP3. HIV-1 sequences were considered recombinant if recombination signals were detected by at least three methods with p-values of ≤0.05 after Bonferroni correction for multiple comparisons. HIV-1 in 38 (84% subjects showed evidence for intra-subtype recombination including 22 with HIV-1 subtype A1, 13 with HIV-1 subtype C, and 3 with HIV-1 subtype D. The distribution of intra-patient recombination breakpoints suggested ongoing recombination and showed selective enrichment of recombinant variants in 23 (60% subjects. The number of subjects with evidence of intra-subtype recombination increased from 29 (69% to 36 (82% over one year of follow-up, although the increase did not reach statistical significance. Adjustment for intra-subtype recombination is important for the analysis of multiplicity of HIV infection. This is the first report of high prevalence of intra-subtype recombination in the HIV/AIDS epidemic in Tanzania, a region where multiple HIV-1 subtypes co-circulate. HIV-1 intra-subtype recombination increases viral diversity and presents additional challenges for HIV-1 vaccine design.

  14. Regional gene expression of LOX-1, VCAM-1, and ICAM-1 in aorta of HIV-1 transgenic rats.

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    Anne Mette Fisker Hag

    Full Text Available BACKGROUND: Increased prevalence of atherosclerotic cardiovascular disease in HIV-infected patients has been observed. The cause of this accelerated atherosclerosis is a matter of controversy. As clinical studies are complicated by a multiplicity of risk-factors and a low incidence of hard endpoints, studies in animal models could be attractive alternatives. METHODOLOGY/PRINCIPAL FINDINGS: We evaluated gene expression of lectin-like oxidized-low-density-lipoprotein receptor-1 (LOX-1, vascular cell adhesion molecule-1 (VCAM-1, and intercellular adhesion molecule-1 (ICAM-1 in HIV-1 transgenic (HIV-1Tg rats; these genes are all thought to play important roles in early atherogenesis. Furthermore, the plasma level of sICAM-1 was measured. We found that gene expressions of LOX-1 and VCAM-1 were higher in the aortic arch of HIV-1Tg rats compared to controls. Also, the level of sICAM-1 was elevated in the HIV-1Tg rats compared to controls, but the ICAM-1 gene expression profile did not show any differences between the groups. CONCLUSIONS/SIGNIFICANCE: HIV-1Tg rats have gene expression patterns indicating endothelial dysfunction and accelerated atherosclerosis in aorta, suggesting that HIV-infection per se may cause atherosclerosis. This transgenic rat model may be a very promising model for further studies of the pathophysiology behind HIV-associated cardiovascular disease.

  15. Assisteret reproduktion ved HIV-infektion

    DEFF Research Database (Denmark)

    Kazlauskaite, Ramune; Østergaard, Lars; Laursen, Tinne

    2009-01-01

    horizontal nor vertical infection occurred. CONCLUSION: Our study confirms that insemination is a good first-choice treatment in respect to chance of pregnancy and risk for virus transmission in HIV-seropositive couples in cases without indication for IVF. Udgivelsesdato: 2009-Apr-27......INTRODUCTION: In Denmark assisted reproductive treatment to HIV discordant couples is offered in order to minimize risk of horizontal transmission of virus. MATERIAL AND METHODS: The outcome of 24 HIV-seropositive couples referred with a wish for parenthood to Aarhus University Hospital, Skejby......, between September 1999 and December 2007 was reviewed on the basis of prospectively collected data. A total of 18 couples were offered treatment. RESULTS: In all, eight couples achieved 17 pregnancies, six by home-insemination, ten by homologous intrauterine insemination, and one spontaneously. Neither...

  16. HIV epidemiology. The early spread and epidemic ignition of HIV-1 in human populations.

    Science.gov (United States)

    Faria, Nuno R; Rambaut, Andrew; Suchard, Marc A; Baele, Guy; Bedford, Trevor; Ward, Melissa J; Tatem, Andrew J; Sousa, João D; Arinaminpathy, Nimalan; Pépin, Jacques; Posada, David; Peeters, Martine; Pybus, Oliver G; Lemey, Philippe

    2014-10-03

    Thirty years after the discovery of HIV-1, the early transmission, dissemination, and establishment of the virus in human populations remain unclear. Using statistical approaches applied to HIV-1 sequence data from central Africa, we show that from the 1920s Kinshasa (in what is now the Democratic Republic of Congo) was the focus of early transmission and the source of pre-1960 pandemic viruses elsewhere. Location and dating estimates were validated using the earliest HIV-1 archival sample, also from Kinshasa. The epidemic histories of HIV-1 group M and nonpandemic group O were similar until ~1960, after which group M underwent an epidemiological transition and outpaced regional population growth. Our results reconstruct the early dynamics of HIV-1 and emphasize the role of social changes and transport networks in the establishment of this virus in human populations. Copyright © 2014, American Association for the Advancement of Science.

  17. HIV-1 protease inhibitory substances from Cassia garrettiana

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    Jindaporn Puripattanvong

    2007-01-01

    Full Text Available Cassia garrettiana Craib, a Thai medicinal plant locally known as Samae-sarn, was investigated for its active constituents against HIV-1 protease (HIV-1 PR. Bioassay-guided fractionation of the heart woodof this plant led to the isolation of a stilbene derivative (1, piceatannol and an anthraquinone derivative (2, chrysophanol. Piceatannol exhibited appreciable inhibitory effect against HIV-1 PR with an IC50 value of25.4 μg/ml, whereas that of chrysophanol was 73.5 μg/ml. In addition, other two stilbenoids together with three anthraquinone derivatives were also investigated for their anti-HIV-1 PR activities. The resultindicated that resveratrol possessed anti-HIV-1 PR activity with an IC50 value of 85.0 μg/ml, whereas other stilbenoid (oxyresveratrol and anthraquinone derivatives (emodin, aloe-emodin, rhein were inactive (IC50 > 100 μg/ml.

  18. The Epidemiology of HIV-1 Transmitted Drug Resistance

    NARCIS (Netherlands)

    D. Frentz (Dineke)

    2012-01-01

    textabstractThe human immunodeficiency virus (HIV) was first discovered in 1983. In 2009, it was estimated that 33.3 (31.4 -35.3) million individuals are infected with HIV worldwide. In that year 1.8 (1.6-2.1) million people died from HIV. Although the virus continues to spread, the number of new

  19. Detection of HIV and HCV RNA in semen from Brazilian coinfected men using multiplex PCR before and after semen washing Detecção do RNA do HIV e HCV em sêmen de homens brasileiros, usando PCR multiplex antes e depois do "semen washing"

    Directory of Open Access Journals (Sweden)

    Cynthia Liliane Motta do Canto

    2006-08-01

    Full Text Available INTRODUCTION: Prolonged survival of patients under HAART has resulted in new demands for assisted reproductive technologies. HIV serodiscordant couples wish to make use of assisted reproduction techniques in order to avoid viral transmission to the partner or to the newborn. It is therefore essential to test the effectiveness of techniques aimed at reducing HIV and HCV loads in infected semen using molecular biology tests. METHODS: After seminal analysis, semen samples from 20 coinfected patients were submitted to cell fractioning and isolation of motile spermatozoa by density gradient centrifugation and swim-up. HIV and HCV RNA detection tests were performed with RNA obtained from sperm, seminal plasma and total semen. RESULTS: In pre-washing semen, HIV RNA was detected in 100% of total semen samples, whereas HCV RNA was concomitantly amplified in only one specimen. Neither HIV nor HCV were detected either in the swim-up or in the post-washing semen fractions. CONCLUSIONS: Reduction of HIV and/or HCV shedding in semen by density gradient centrifugation followed by swim-up is an efficient method. These findings lead us to believe that, although semen is rarely found to contain HCV, semen processing is highly beneficial for HIV/HCV coinfected individuals.O aumento da sobrevida dos pacientes que utilizam terapêutica antiretroviral altamente eficaz (HAART- Highly Active Antiretroviral Therapy trouxe uma nova demanda de casais sorodiscordantes que desejam filhos. Como esses casais não podem abandonar o uso de preservativos, torna-se indispensável tratar o sêmen infectado com técnicas laboratoriais eficazes que além de isolar os melhores espermatozóides, reduzam a carga viral do HIV e HCV a níveis indetectáveis. Para isso, são utilizadas técnicas de semen washing, associadas a testes ultra sensíveis de biologia molecular. Após análise seminal, sêmen de 20 pacientes co-infectados HIV-HCV foram submetidos a fracionamento celular e

  20. The Depsipeptide Romidepsin Reverses HIV-1 Latency In Vivo.

    Directory of Open Access Journals (Sweden)

    Ole S Søgaard

    2015-09-01

    Full Text Available Pharmacologically-induced activation of replication competent proviruses from latency in the presence of antiretroviral treatment (ART has been proposed as a step towards curing HIV-1 infection. However, until now, approaches to reverse HIV-1 latency in humans have yielded mixed results. Here, we report a proof-of-concept phase Ib/IIa trial where 6 aviremic HIV-1 infected adults received intravenous 5 mg/m2 romidepsin (Celgene once weekly for 3 weeks while maintaining ART. Lymphocyte histone H3 acetylation, a cellular measure of the pharmacodynamic response to romidepsin, increased rapidly (maximum fold range: 3.7–7.7 relative to baseline within the first hours following each romidepsin administration. Concurrently, HIV-1 transcription quantified as copies of cell-associated un-spliced HIV-1 RNA increased significantly from baseline during treatment (range of fold-increase: 2.4–5.0; p = 0.03. Plasma HIV-1 RNA increased from <20 copies/mL at baseline to readily quantifiable levels at multiple post-infusion time-points in 5 of 6 patients (range 46–103 copies/mL following the second infusion, p = 0.04. Importantly, romidepsin did not decrease the number of HIV-specific T cells or inhibit T cell cytokine production. Adverse events (all grade 1–2 were consistent with the known side effects of romidepsin. In conclusion, romidepsin safely induced HIV-1 transcription resulting in plasma HIV-1 RNA that was readily detected with standard commercial assays demonstrating that significant reversal of HIV-1 latency in vivo is possible without blunting T cell-mediated immune responses. These finding have major implications for future trials aiming to eradicate the HIV-1 reservoir.clinicaltrials.gov NTC02092116.

  1. Clustering patterns of cytotoxic T-lymphocyte epitopes in human immunodeficiency virus type 1 (HIV-1) proteins reveal imprints of immune evasion on HIV-1 global variation

    DEFF Research Database (Denmark)

    Yusim, K.; Kesmir, Can; Gaschen, B.

    2002-01-01

    The human cytotoxic T-lymphocyte (CTL) response to human immunodeficiency virus type 1 (HIV-1) has been intensely studied, and hundreds of CTL epitopes have been experimentally defined, published, and compiled in the HIV Molecular Immunology Database. Maps of CTL epitopes on HIV-1 protein sequenc...

  2. HIV-1 impairs human retinal pigment epithelial barrier function: possible association with the pathogenesis of HIV-associated retinopathy.

    Science.gov (United States)

    Tan, Suiyi; Duan, Heng; Xun, Tianrong; Ci, Wei; Qiu, Jiayin; Yu, Fei; Zhao, Xuyan; Wu, Linxuan; Li, Lin; Lu, Lu; Jiang, Shibo; Liu, Shuwen

    2014-07-01

    The breakdown of human retinal pigment epithelial (HRPE) barrier is considered as the etiology of retinopathy, which affects the quality of life of HIV/AIDS patients. Here we demonstrate that HIV-1 could directly impair HRPE barrier function, which leads to the translocation of HIV-1 and bacteria. HRPE cells (D407) were grown to form polarized, confluent monolayers and treated with different HIV-1 infectious clones. A significant increase of monolayer permeability, as measured by trans-epithelial electrical resistance (TEER) and apical-basolateral movements of sodium fluorescein, was observed. Disrupted tightness of HRPE barrier was associated with the downregulation of several tight junction proteins in D407 cells, including ZO-1, Occludin, Claudin-1, Claudin-2, Claudin-3, Claudin-4, and Claudin-5, after exposure to HIV-1, without affecting the viability of cells. HIV-1 gp120 was shown to participate in the alteration of barrier properties, as evidenced by decreased TEER and weakened expression of tight junction proteins in D407 monolayers after exposure to pseudotyped HIV-1, UV-inactivated HIV-1, and free gp120, but not to an envelope (Env)-defective mutant of HIV. Furthermore, exposure to HIV-1 particles could induce the release of pro-inflammatory cytokines in D407, including IL-6 and MCP-1, both of which downregulated the expression of ZO-1 in the HRPE barrier. Disrupted HRPE monolayer allowed translocation of HIV-1 and bacteria across the epithelium. Overall, these findings suggest that HIV-1 may exploit its Env glycoprotein to induce an inflammatory state in HRPE cells, which could result in impairment of HRPE monolayer integrity, allowing virus and bacteria existing in ocular fluids to cross the epithelium and penetrate the HRPE barrier. Our study highlights the role of HIV-1 in the pathogenesis of HIV/AIDS-related retinopathy and suggests potential therapeutic targets for this ocular complication.

  3. Trends of HIV-1, HIV-2 and dual infection in women attending outpatient clinics in Senegal, 1990–2009

    Science.gov (United States)

    Heitzinger, K; Sow, P S; Badiane, N M Dia; Gottlieb, G S; N’Doye, I; Toure, M; Kiviat, N B; Hawes, S E

    2013-01-01

    Summary We assessed trends in the relative prevalences of HIV-1, HIV-2 and dual HIV-1/HIV-2 infection in 10,321 women attending outpatient clinics in Senegal between 1990 and 2009. The relative prevalence of HIV-1 (defined as the proportion of seropositive subjects having HIV-1) rose sharply from 38% in 1990 until 1993 (P Senegal. From 1993 to 2009, the relative prevalence of HIV-1 increased at a slower rate, while the relative prevalences of HIV-2 and dual infection decreased. These results confirm trends in HIV prevalence observed in other West African populations and provide a critical update on HIV transmission risk among women in Senegal. PMID:23104745

  4. Structure of HIV-1 protease determined by neutron crystallography

    International Nuclear Information System (INIS)

    Adachi, Motoyasu; Kuroki, Ryota

    2009-01-01

    HIV-1 protease is an aspartic protease, and plays an essential role in replication of HIV. To develop HIV-1 protease inhibitors through structure-based drug design, it is necessary to understand the catalytic mechanism and inhibitor recognition of HIV-1 protease. We have determined the crystal structure of HIV-1 protease in complex with KNI-272 to 1.9 A resolution by neutron crystallography in combination with 1.4 A resolution X-ray diffraction data. The results show that the carbonyl group of hydroxymethylcarbonyl (HMC) in KNI-272 forms a hydrogen bonding interaction with protonated Asp 25 and the hydrogen atom from the hydroxyl group of HMC forms a hydrogen bonding interaction with the deprotonated Asp125. This is the first neutron report for HIV-1/inhibitor complex and shows directly the locations of key hydrogen atoms in catalysis and in the binding of a transition-state analog. The results confirm key aspect of the presumed catalytic mechanism of HIV-1 protease and will aid in the further development of protease inhibitors. (author)

  5. Molecular Basis for Drug Resistance in HIV-1 Protease

    Directory of Open Access Journals (Sweden)

    Celia A. Schiffer

    2010-11-01

    Full Text Available HIV-1 protease is one of the major antiviral targets in the treatment of patients infected with HIV-1. The nine FDA approved HIV-1 protease inhibitors were developed with extensive use of structure-based drug design, thus the atomic details of how the inhibitors bind are well characterized. From this structural understanding the molecular basis for drug resistance in HIV-1 protease can be elucidated. Selected mutations in response to therapy and diversity between clades in HIV-1 protease have altered the shape of the active site, potentially altered the dynamics and even altered the sequence of the cleavage sites in the Gag polyprotein. All of these interdependent changes act in synergy to confer drug resistance while simultaneously maintaining the fitness of the virus. New strategies, such as incorporation of the substrate envelope constraint to design robust inhibitors that incorporate details of HIV-1 protease’s function and decrease the probability of drug resistance, are necessary to continue to effectively target this key protein in HIV-1 life cycle.

  6. Comparison of glycerolisation with cryopreservation methods on HIV-1 inactivation

    International Nuclear Information System (INIS)

    Van Baare, J.; Pagnon, J.; Cameron, P.; Vardaxis, N.; Middlekoop, E.; Crowe, S.

    1999-01-01

    Cryopreservation and glycerolisation are two successful long-term preservation methods for human cadaveric donor skin, which is used in the treatment of bum patients. High concentrations of glycerol has been shown to be antibacterial and virucidal. Because fear of possible transmission of HIV-1 following allograft transplantation, this study was undertaken to investigate whether HIV can be effectively eliminated from skin explants. HIV-1 Ba-L, which has been shown to infect monocytes in skin explants and also dendritic cells, was. For the experiments we used cell-free virus, exogenously HIV infected peripheral blood mononuclear cells (PBMCs) and exogenously HIV infected cadaver split skin. Different concentrations of glycerol at various temperatures and the glycerolisation procedure as used by the Euro Skin Bank were used to determine the effects on HIV-1 Ba-L infectivity. For the cryopreservation technique we used 10% DMSO and a controlled rate freezer. HIV-1 Ba-L transfer was determined by adding uninfected PBMCs to the infected material and reverse transcriptase was measured. Cell-free HIV-1 Ba-L was not inactivated by 50% glycerol but was effectively inactivated within 30 minutes by 70% and 85% glycerol at 4 degree C, room temperature and 37 degree C. In contrast, cell-free HIV-1 Ba-L was not inactivated by cryopreservation. Most importantly, we have shown that HIV-1 Ba-L present in split skin is inactivated by incubating skin in 70% glycerol for three hours at 37-C. HIV in exogenously infected skin was not inactivated by cryopreservation. High concentrations of glycerol effectively inactivates free HIV-1 Ba-L and intracellular HIV-1 Ba-L. Also the current glycerolisation procedure carried out by the Euro Skin Bank effectively inactivates infectious virus. However, the cryopreservation technique did not show any reduction in HIV-1 Ba-L infectivity

  7. Perceived Advantages and Disadvantages of Using Pre-Exposure Prophylaxis (PrEP) among Sexually Active Black Women: An Exploratory Study.

    Science.gov (United States)

    Bond, Keosha T; Gunn, Alana J

    2016-01-01

    Knowledge of pre-exposure prophylaxis (PrEP) continues to remain scarce among Black women who are disproportionally affected by HIV in the United States. A thematic analysis of open-ended questions from a sample of Black women (n=119) who completed a mix-methods, online, e-health study was conducted to examine the perceived advantages and disadvantages of using PrEP. Being a female controlled method, empowerment, option for women with risky sex partners, and serodiscordant couples were advantages described. Disadvantages of PrEP were identified as the complexity of the choice, encouragement of sex with risky partners, increased burden, promotion of unprotected sex, and newness of the drug.

  8. Perceived Advantages and Disadvantages of Using Pre-Exposure Prophylaxis (PrEP) among Sexually Active Black Women

    Science.gov (United States)

    Bond, Keosha T.; Gunn, Alana J.

    2017-01-01

    Knowledge of pre-exposure prophylaxis (PrEP) continues to remain scarce among Black women who are disproportionally affected by HIV in the United States. A thematic analysis of open-ended questions from a sample of Black women (n=119) who completed a mix-methods, online, e-health study was conducted to examine the perceived advantages and disadvantages of using PrEP. Being a female controlled method, empowerment, option for women with risky sex partners, and serodiscordant couples were advantages described. Disadvantages of PrEP were identified as the complexity of the choice, encouragement of sex with risky partners, increased burden, promotion of unprotected sex, and newness of the drug. PMID:28725660

  9. An anti-HIV microbicide engineered in commensal bacteria: secretion of HIV-1 fusion inhibitors by lactobacilli

    NARCIS (Netherlands)

    Pusch, O.; Kalyanaraman, R.; Tucker, L.D.; Wells, J.; Rmanratnam, B.; Boden, D.

    2006-01-01

    Objectives: To engineer Lactobacillus spp. to secrete HIV-1 fusion inhibitors with potent neutralizing activity against primary HIV-1 isolates. Methods: HIV-1 fusion inhibitors (FI-1, FI-2, and FI-3) were introduced into the previously developed shuttle vector pTSV2 and transformed in L. plantarum

  10. Exosomes from Human Immunodeficiency Virus Type 1 (HIV-1)-Infected Cells License Quiescent CD4+ T Lymphocytes To Replicate HIV-1 through a Nef- and ADAM17-Dependent Mechanism

    OpenAIRE

    Arenaccio, Claudia; Chiozzini, Chiara; Columba-Cabezas, Sandra; Manfredi, Francesco; Affabris, Elisabetta; Baur, Andreas; Federico, Maurizio

    2014-01-01

    Resting CD4+ T lymphocytes resist human immunodeficiency virus (HIV) infection. Here, we provide evidence that exosomes from HIV-1-infected cells render resting human primary CD4+ T lymphocytes permissive to HIV-1 replication. These results were obtained with transwell cocultures of HIV-1-infected cells with quiescent CD4+ T lymphocytes in the presence of inhibitors of exosome release and were confirmed using exosomes purified from supernatants of HIV-1-infected primary CD4+ T lymphocytes. We...

  11. Uso de condom feminino por mulheres infectadas pelo HIV Female condom use among HIV-infected women

    Directory of Open Access Journals (Sweden)

    Jarbas Magalhães

    2003-07-01

    -infected women under care at CAISM/UNICAMP and Centro Corsini, both in Campinas. After a screening interview and agreeing to participate, the volunteers received a diary to register their intercourses and correspondent use of male condom (MC. After 30 days, they returned to a training visit when the FC was inserted in a pelvic model, also bringing their diary related to the previous cycle, considered a control cycle. A structured questionnaire was used at 30, 60 and 90 days, also with the respective diary on sexual intercourse and use of MC and FC kept for posterior data entry. c², Fisher's exact, McNemar and Friedman tests were applied statistical analysis of paired samples. RESULTS: there was a predominance of young women, with low schooling, living with their partner. Rate of continuity was 52% after 90 days. The use of FC in half the intercourses for each time period remained stable over the 90-day interval. There was a significant reduction in unprotected intercourses (from 14 to 6%, without use of FC or MC, at the end of the period. The initial difficulties in handling the device were overcome. Serodiscordant couples had more protected intercourses than concordant couples, but the difference did not reach statistical significance. Women reporting consistent previous use of MC had more protected sex using FC. CONCLUSIONS: the offer of the female condom was able to reduce unprotected intercourses in HIV-infected women, which were highly motivated and receptive for the new method.

  12. Sexual communication self-efficacy, hegemonic masculine norms and condom use among heterosexual couples in South Africa.

    Science.gov (United States)

    Leddy, Anna; Chakravarty, Deepalika; Dladla, Sibongile; de Bruyn, Guy; Darbes, Lynae

    2016-01-01

    Hegemonic masculine norms (HMN), which promote sexual risk-taking among males and the subordination of women, are believed to play a key role in the HIV epidemic among heterosexual couples in South Africa (SA). Sexual communication self-efficacy (SCSE) (i.e., a couple's confidence in their ability to communicate about HIV prevention) may be a key leverage point for increasing HIV prevention behaviors among this population. We interviewed 163 sexually active heterosexual couples in Soweto, SA to investigate the association between SCSE, HMN, and consistent condom use. We collected information on demographics, relationship dynamics, and sexual activity. We utilized the SCSE scale to measure couples' SCSE, and a subscale of the Gender Equitable Men scale to measure HMN among males. We performed bivariate and multivariable analyses to determine the association of consistent condom use with couples' SCSE as well as the male partner's endorsement of HMN. We found that couples with higher SCSE have greater odds of consistent condom use (adjusted odds ratio [AOR] = 1.30, 95% CI: 1.15-1.47). Furthermore, male endorsement of HMN was found to be negatively associated with consistent condom use among couples (AOR = 0.47, 95% CI: 0.24-0.89). Joint HIV serostatus was not significantly associated with the outcome. Future interventions that equip heterosexual couples with sexual communication skills, while simultaneously promoting more gender equitable norms, may increase consistent condom use and thereby reduce the transmission of HIV among this at-risk population.

  13. Rational development of radiopharmaceuticals for HIV-1

    International Nuclear Information System (INIS)

    Lau, Chuen-Yen; Maldarelli, Frank; Eckelman, William C.; Neumann, Ronald D.

    2014-01-01

    The global battle against HIV-1 would benefit from a sensitive and specific radiopharmaceutical to localize HIV-infected cells. Ideally, this probe would be able to identify latently infected host cells containing replication competent HIV sequences. Clinical and research applications would include assessment of reservoirs, informing clinical management by facilitating assessment of burden of infection in different compartments, monitoring disease progression and monitoring response to therapy. A “rational” development approach could facilitate efficient identification of an appropriate targeted radiopharmaceutical. Rational development starts with understanding characteristics of the disease that can be effectively targeted and then engineering radiopharmaceuticals to hone in on an appropriate target, which in the case of HIV-1 (HIV) might be an HIV-specific product on or in the host cell, a differentially expressed gene product, an integrated DNA sequence specific enzymatic activity, part of the inflammatory response, or a combination of these. This is different from the current approach that starts with a radiopharmaceutical for a target associated with a disease, mostly from autopsy studies, without a strong rationale for the potential to impact patient care. At present, no targeted therapies are available for HIV latency, although a number of approaches are under study. Here we discuss requirements for a radiopharmaceutical useful in strategies targeting persistently infected cells. The radiopharmaceutical for HIV should be developed based on HIV biology, studied in an animal model and then in humans, and ultimately used in clinical and research settings

  14. Novel host restriction factors implicated in HIV-1 replication.

    Science.gov (United States)

    Ghimire, Dibya; Rai, Madhu; Gaur, Ritu

    2018-04-01

    Human immunodeficiency virus-1 (HIV-1) is known to interact with multiple host cellular proteins during its replication in the target cell. While many of these host cellular proteins facilitate viral replication, a number of them are reported to inhibit HIV-1 replication at various stages of its life cycle. These host cellular proteins, which are known as restriction factors, constitute an integral part of the host's first line of defence against the viral pathogen. Since the discovery of apolipoprotein B mRNA-editing enzyme 3G (APOBEC3G) as an HIV-1 restriction factor, several human proteins have been identified that exhibit anti-HIV-1 restriction. While each restriction factor employs a distinct mechanism of inhibition, the HIV-1 virus has equally evolved complex counter strategies to neutralize their inhibitory effect. APOBEC3G, tetherin, sterile alpha motif and histidine-aspartate domain 1 (SAMHD1), and trim-5α are some of the best known HIV-1 restriction factors that have been studied in great detail. Recently, six novel restriction factors were discovered that exhibit significant antiviral activity: endoplasmic reticulum α1,2-mannosidase I (ERManI), translocator protein (TSPO), guanylate-binding protein 5 (GBP5), serine incorporator (SERINC3/5) and zinc-finger antiviral protein (ZAP). The focus of this review is to discuss the antiviral mechanism of action of these six restriction factors and provide insights into the probable counter-evasion strategies employed by the HIV-1 virus. The recent discovery of new restriction factors substantiates the complex host-pathogen interactions occurring during HIV-1 pathogenesis and makes it imperative that further investigations are conducted to elucidate the molecular basis of HIV-1 replication.

  15. HIV-1 persistence following extremely early initiation of antiretroviral therapy (ART during acute HIV-1 infection: An observational study.

    Directory of Open Access Journals (Sweden)

    Timothy J Henrich

    2017-11-01

    Full Text Available It is unknown if extremely early initiation of antiretroviral therapy (ART may lead to long-term ART-free HIV remission or cure. As a result, we studied 2 individuals recruited from a pre-exposure prophylaxis (PrEP program who started prophylactic ART an estimated 10 days (Participant A; 54-year-old male and 12 days (Participant B; 31-year-old male after infection with peak plasma HIV RNA of 220 copies/mL and 3,343 copies/mL, respectively. Extensive testing of blood and tissue for HIV persistence was performed, and PrEP Participant A underwent analytical treatment interruption (ATI following 32 weeks of continuous ART.Colorectal and lymph node tissues, bone marrow, cerebral spinal fluid (CSF, plasma, and very large numbers of peripheral blood mononuclear cells (PBMCs were obtained longitudinally from both participants and were studied for HIV persistence in several laboratories using molecular and culture-based detection methods, including a murine viral outgrowth assay (mVOA. Both participants initiated PrEP with tenofovir/emtricitabine during very early Fiebig stage I (detectable plasma HIV-1 RNA, antibody negative followed by 4-drug ART intensification. Following peak viral loads, both participants experienced full suppression of HIV-1 plasma viremia. Over the following 2 years, no further HIV could be detected in blood or tissue from PrEP Participant A despite extensive sampling from ileum, rectum, lymph nodes, bone marrow, CSF, circulating CD4+ T cell subsets, and plasma. No HIV was detected from tissues obtained from PrEP Participant B, but low-level HIV RNA or DNA was intermittently detected from various CD4+ T cell subsets. Over 500 million CD4+ T cells were assayed from both participants in a humanized mouse outgrowth assay. Three of 8 mice infused with CD4+ T cells from PrEP Participant B developed viremia (50 million input cells/surviving mouse, but only 1 of 10 mice infused with CD4+ T cells from PrEP Participant A (53 million input

  16. HIV-1 replication in cell lines harboring INI1/hSNF5 mutations

    Directory of Open Access Journals (Sweden)

    Wu Xuhong

    2006-08-01

    Full Text Available Abstract Background INI1/hSNF5 is a cellular protein that directly interacts with HIV-1 integrase (IN. It is specifically incorporated into HIV-1 virions. A dominant negative mutant derived from INI1 inhibits HIV-1 replication. Recent studies indicate that INI1 is associated with pre-integration and reverse transcription complexes that are formed upon viral entry into the target cells. INI1 also is a tumor suppressor, biallelically deleted/mutated in malignant rhabdoid tumors. We have utilized cell lines derived from the rhabdoid tumors, MON and STA-WT1, that harbor either null or truncating mutations of INI1 respectively, to assess the effect of INI1 on HIV-1 replication. Results We found that while HIV-1 virions produced in 293T cells efficiently transduced MON and STA-WT1 cells, HIV-1 particle production was severely reduced in both of these cells. Reintroduction of INI1 into MON and STA-WT1 significantly enhanced the particle production in both cell lines. HIV-1 particles produced in MON cells were reduced for infectivity, while those produced in STA-WT1 were not. Further analysis indicated the presence of INI1 in those virions produced from STA-WT1 but not from those produced from MON cells. HIV-1 produced in MON cells were defective for synthesis of early and late reverse transcription products in the target cells. Furthermore, virions produced in MON cells were defective for exogenous reverse transcriptase activity carried out using exogenous template, primer and substrate. Conclusion Our results suggest that INI1-deficient cells exhibit reduced particle production that can be partly enhanced by re-introduction of INI1. Infectivity of HIV-1 produced in some but not all INI1 defective cells, is affected and this defect may correlate to the lack of INI1 and/or some other proteins in these virions. The block in early events of virion produced from MON cells appears to be at the stage of reverse transcription. These studies suggest that

  17. HIV-1 replication in cell lines harboring INI1/hSNF5 mutations.

    Science.gov (United States)

    Sorin, Masha; Yung, Eric; Wu, Xuhong; Kalpana, Ganjam V

    2006-08-31

    INI1/hSNF5 is a cellular protein that directly interacts with HIV-1 integrase (IN). It is specifically incorporated into HIV-1 virions. A dominant negative mutant derived from INI1 inhibits HIV-1 replication. Recent studies indicate that INI1 is associated with pre-integration and reverse transcription complexes that are formed upon viral entry into the target cells. INI1 also is a tumor suppressor, biallelically deleted/mutated in malignant rhabdoid tumors. We have utilized cell lines derived from the rhabdoid tumors, MON and STA-WT1, that harbor either null or truncating mutations of INI1 respectively, to assess the effect of INI1 on HIV-1 replication. We found that while HIV-1 virions produced in 293T cells efficiently transduced MON and STA-WT1 cells, HIV-1 particle production was severely reduced in both of these cells. Reintroduction of INI1 into MON and STA-WT1 significantly enhanced the particle production in both cell lines. HIV-1 particles produced in MON cells were reduced for infectivity, while those produced in STA-WT1 were not. Further analysis indicated the presence of INI1 in those virions produced from STA-WT1 but not from those produced from MON cells. HIV-1 produced in MON cells were defective for synthesis of early and late reverse transcription products in the target cells. Furthermore, virions produced in MON cells were defective for exogenous reverse transcriptase activity carried out using exogenous template, primer and substrate. Our results suggest that INI1-deficient cells exhibit reduced particle production that can be partly enhanced by re-introduction of INI1. Infectivity of HIV-1 produced in some but not all INI1 defective cells, is affected and this defect may correlate to the lack of INI1 and/or some other proteins in these virions. The block in early events of virion produced from MON cells appears to be at the stage of reverse transcription. These studies suggest that presence of INI1 or some other host factor in virions and

  18. HIV-1 infection during pregnancy and in children : significance of HIV-1 variability and the placental barrier

    OpenAIRE

    Casper, Charlotte

    2001-01-01

    With the global increase in human immunodeficiency virus 1 (HIV-1) infection in women of childbearing age, there has also been an alarming increase in the number of mother-to-child transmissions of HIV-1. Although antiretroviral therapy and Cesarian section have been demonstrated to significantly decrease the vertical transmission rate of , these interventions are not widely available in the developing world. Therefore, studies of the mechanisms of vertical transmission are ...

  19. CCL28 induces mucosal homing of HIV-1-specific IgA-secreting plasma cells in mice immunized with HIV-1 virus-like particles.

    Directory of Open Access Journals (Sweden)

    Veronica Rainone

    Full Text Available Mucosae-associated epithelial chemokine (MEC or CCL28 binds to CCR3 and CCR10 and recruits IgA-secreting plasma cells (IgA-ASCs in the mucosal lamina propria. The ability of this chemokine to enhance migration of IgA-ASCs to mucosal sites was assessed in a mouse immunization model using HIV-1(IIIB Virus-like particles (VLPs. Mice receiving either HIV-1(IIIB VLPs alone, CCL28 alone, or the irrelevant CCL19 chemokine were used as controls. Results showed a significantly increased CCR3 and CCR10 expression on CD19(+ splenocytes of HIV-1(IIIB VPL-CCL28-treated mice. HIV-1 Env-specific IFN-γ, IL-4 and IL-5 production, total IgA, anti-Env IgA as well as gastro-intestinal mucosal IgA-secreting plasma cells were also significantly augmented in these mice. Notably, sera and vaginal secretions from HIV-1(IIIB VLP-CCL28-treated mice exhibited an enhanced neutralizing activity against both a HIV-1/B-subtype laboratory strain and a heterologous HIV-1/C-subtype primary isolate. These data suggest that CCL28 could be useful in enhancing the IgA immune response that will likely play a pivotal role in prophylactic HIV vaccines.

  20. Antiviral Therapy by HIV-1 Broadly Neutralizing and Inhibitory Antibodies

    Directory of Open Access Journals (Sweden)

    Zhiqing Zhang

    2016-11-01

    Full Text Available Human immunodeficiency virus type 1 (HIV-1 infection causes acquired immune deficiency syndrome (AIDS, a global epidemic for more than three decades. HIV-1 replication is primarily controlled through antiretroviral therapy (ART but this treatment does not cure HIV-1 infection. Furthermore, there is increasing viral resistance to ART, and side effects associated with long-term therapy. Consequently, there is a need of alternative candidates for HIV-1 prevention and therapy. Recent advances have discovered multiple broadly neutralizing antibodies against HIV-1. In this review, we describe the key epitopes on the HIV-1 Env protein and the reciprocal broadly neutralizing antibodies, and discuss the ongoing clinical trials of broadly neutralizing and inhibitory antibody therapy as well as antibody combinations, bispecific antibodies, and methods that improve therapeutic efficacy by combining broadly neutralizing antibodies (bNAbs with latency reversing agents. Compared with ART, HIV-1 therapeutics that incorporate these broadly neutralizing and inhibitory antibodies offer the advantage of decreasing virus load and clearing infected cells, which is a promising prospect in HIV-1 prevention and treatment.

  1. Molecular mechanisms of HIV-1 associated neurodegeneration

    Indian Academy of Sciences (India)

    Since identification of the human immunodeficiency virus-1 (HIV-1), numerous studies suggest a link between neurological impairments, in particular dementia, with acquired immunodeficiency syndrome (AIDS) with alarming occurrence worldwide. Approximately, 60% of HIV-infected people show some form of neurological ...

  2. Viral dynamics in primary HIV-1 infection. Karolinska Institutet Primary HIV Infection Study Group.

    Science.gov (United States)

    Lindbäck, S; Karlsson, A C; Mittler, J; Blaxhult, A; Carlsson, M; Briheim, G; Sönnerborg, A; Gaines, H

    2000-10-20

    To study the natural course of viremia during primary HIV infection (PHI). Eight patients were followed from a median of 5 days from the onset of PHI illness. Plasma HIV-1 RNA levels were measured frequently and the results were fitted to mathematical models. HIV-1 RNA levels were also monitored in nine patients given two reverse transcriptase inhibitors and a protease inhibitor after a median of 7 days from the onset of PHI illness. HIV-1 RNA appeared in the blood during the week preceding onset of PHI illness and increased rapidly during the first viremic phase, reaching a peak at a mean of 7 days after onset of illness. This was followed by a phase of rapidly decreasing levels of HIV-1 RNA to an average of 21 days after onset. Viral density continued to decline thereafter but at a 5- to 50-fold lower rate; a steady-state level was reached at a median of 2 months after onset of PHI. Peak viral density levels correlated significantly with levels measured between days 50 and 600. Initiation of antiretroviral treatment during PHI resulted in rapidly declining levels to below 50 copies/mL. This study demonstrates the kinetic phases of viremia during PHI and indicates two new contributions to the natural history of HIV-1 infection: PHI peak levels correlate with steady-state levels and HIV-1 RNA declines biphasically; an initial rapid decay is usually followed by a slow decay, which is similar to the initial changes seen with antiviral treatment.

  3. Evaluation of four rapid tests for diagnosis and differentiation of HIV-1 and HIV-2 infections in Guinea-Conakry, West Africa.

    OpenAIRE

    Chaillet, Pascale; Tayler-Smith, Katie; Zachariah, Rony; Duclos, Nanfack; Moctar, Diallo; Beelaert, Greet; Fransen, Katrien

    2010-01-01

    With both HIV-1 and HV-2 prevalent in Guinea-Conakry, accurate diagnosis and differentiation is crucial for treatment purposes. Thus, four rapid HIV tests were evaluated for their HIV-1 and HIV-2 diagnostic and discriminative capacity for use in Guinea-Conakry. These included SD Bioline HIV 1/2 3.0 (Standard Diagnostics Inc.), Genie II HIV1/HIV2 (Bio-Rad), First Response HIV Card Test 1-2.0 (PMC Medical) and Immunoflow HIV1-HIV2 (Core Diagnostics). Results were compared with gold standard tes...

  4. Cerebrospinal fluid HIV-1 RNA levels in asymptomatic patients with early stage chronic HIV-1 infection: support for the hypothesis of local virus replication.

    Science.gov (United States)

    García, F; Niebla, G; Romeu, J; Vidal, C; Plana, M; Ortega, M; Ruiz, L; Gallart, T; Clotet, B; Miró, J M; Pumarola, T; Gatell, J M

    1999-08-20

    To assess HIV-1 RNA levels in cerebrospinal fluid (CSF) and their potential correlation with plasma viral load and central nervous system (CNS) HIV-1 infection markers in stable asymptomatic patients with a CD4 T cell count >500x10(6) cells/l. Consecutive patients screened for two trials were eligible for lumbar puncture assessment. At day 0, simultaneous samples of CSF and plasma were obtained and levels of total proteins, albumin, IgG, antibodies against HIV-1 p24 antigen, HIV-1 RNA (using the polymerase chain technique) and white cells were measured. The integrity of the blood-brain barrier was preserved (albumin index > or =7) in 59 out of 70 patients (84%). Intrathecal production of antibodies against HIV-1 p24 antigen was demonstrated in 55 out of 70 individuals (78%). Viral load in CSF was significantly lower than plasma values (3.13+/-0.95 versus 4.53+/-0.53, P = 0.0001). HIV-1 RNA was not detected in CSF in only three of the 70 patients (4%). Overall, there was a significant correlation between plasma and CSF HIV-1 RNA levels (r = 0.43, P = 0.0001); however, in 29 patients (41%) there were significant differences (>1.5 log10 copies/ml) between the viral loads in plasma and CSF. In the multivariate analysis, a high level of protein and white cells in CSF, but not the HIV-1 RNA plasma level, were factors independently associated with a higher level of HIV-1 RNA in CSF (P = 0.0001). HIV-1 RNA can be detected almost always in CSF of asymptomatic patients in early stages of HIV-1 infection including those with a preserved integrity of the blood-brain barrier. The important discrepancies between plasma and CSF viral load, and the independent association between CSF abnormalities and CSF viral load, support the hypothesis of local production of HIV-1.

  5. Characteristics of HIV-2 and HIV-1/HIV-2 Dually Seropositive Adults in West Africa Presenting for Care and Antiretroviral Therapy

    DEFF Research Database (Denmark)

    Ekouevi, Didier K; Balestre, Eric; Coffie, Patrick A

    2013-01-01

    HIV-2 is endemic in West Africa. There is a lack of evidence-based guidelines on the diagnosis, management and antiretroviral therapy (ART) for HIV-2 or HIV-1/HIV-2 dual infections. Because of these issues, we designed a West African collaborative cohort for HIV-2 infection within the framework o...... of the International epidemiological Databases to Evaluate AIDS (IeDEA)....

  6. HIV-1 subtypes D and F are prevalent in Guinea Conakry.

    Science.gov (United States)

    Freimanis, G L; Loua, A; Allain, J P

    2012-04-01

    Limited data is available upon the distribution of different HIV-1/2 genotypes in the blood donor population from Guinea Conakry. To investigate the prevalence of HIV-1/2 subtypes in asymptomatic blood donors in Guinea Conakry, in order to update knowledge of HIV-1/2 epidemiology within this country. Samples from 104 blood donors seropositive for HIV-1/2 were tested for HIV-1 by real-time RT-PCR. Those negative for HIV-1 were tested with HIV-2 nested RT-PCR. Positive samples were further amplified in the HIV-1 gag and pol regions and sequenced. Subtypes were determined by phylogenetic analysis on amplicon sequences. 61 samples were positive by HIV-1 real-time RT-PCR. Of the 43 negative, 2 (4.6%) were positive for HIV-2. 52/61 (85.3%) samples were positive by nested RT-PCR. Of the 52, 43 (70.5%) and 31(59.6%) sequences were obtained in the gag and pol regions, respectively; 23 for both regions. HIV-1 subtype distribution was 1 B (2.1%), 8 F (17%), 8 D (17%) and 28 CRF02_AG (59.6%) with 2 unclassified recombinants (4.3%). Unique clusters for subtype D and F distinguished Guinea from HIV-1 subtype distribution in neighboring countries. Subtype F and subtype D strains, uncommon in West Africa, are a substantial part of HIV-1 epidemiology in Guinea. Copyright © 2011 Elsevier B.V. All rights reserved.

  7. Physician attitudes regarding pregnancy, fertility care, and assisted reproductive technologies for HIV-infected individuals and couples.

    Science.gov (United States)

    Yudin, Mark H; Money, Deborah M; Cheung, Matthew C; Loutfy, Mona R

    2012-01-01

    Family and pregnancy planning are important for HIV-infected individuals and couples. There is a paucity of data regarding physician attitudes with respect to reproduction in this population, but some evidence suggests that attitudes can influence the information, advice, and services they will provide. To determine physician attitudes toward pregnancy, fertility care, and access to assisted reproductive technologies for HIV-infected individuals, and to determine whether attitudes differed based on specific physician characteristics. A survey was sent electronically to obstetrician/gynecologists and infectious disease specialists in Canada. Items were grouped into 5 key domains: physician demographics, physician attitudes toward pregnancy and adoption, physician attitudes toward fertility care, physician attitudes toward assisted reproductive technology, and challenges for an HIV-infected population. Attitudes were determined based on answers to individual questions and also for each domain. Univariate and logistic regression analyses were used to determine the influence of specific physician characteristics on attitudes. Completed surveys were received from 165 physicians. Most had positive attitudes regarding pregnancy or adoption (89%), fertility care (72%), and assisted reproductive technology (79%). In multivariate analyses, having cared for HIV-infected patients was significantly associated with having a positive attitude toward fertility care or assisted reproductive technology. In this national survey of Canadian physicians, most had positive attitudes toward pregnancy, adoption, fertility care, and use of assisted reproductive technology among HIV-infected persons. Physicians who had cared for HIV-infected individuals in the past were more likely to have positive attitudes than those who had not.

  8. Minor drug-resistant HIV type-1 variants in breast milk and plasma of HIV type-1-infected Ugandan women after nevirapine single-dose prophylaxis.

    Science.gov (United States)

    Pilger, Daniel; Hauser, Andrea; Kuecherer, Claudia; Mugenyi, Kizito; Kabasinguzi, Rose; Somogyi, Sybille; Harms, Gundel; Kunz, Andrea

    2011-01-01

    Nevirapine single-dose (NVP-SD) reduces mother-to-child transmission of HIV type-1 (HIV-1), but frequently induces resistance mutations in the HIV-1 genome. Little is known about drug-resistant HIV-1 variants in the breast milk of women who have taken NVP-SD. Blood and breast milk samples of 39 HIV-1-infected Ugandan women were taken 6-12 weeks after NVP-SD intake. Samples were analysed by population sequencing and allele-specific real-time PCR (AS-PCR) with detection limits for NVP-resistant HIV-1 variants (K103N and Y181C) of D n = 5, G n = 2 and C n = 1). A total of 7 (37%) and 10 (53%) women carried NVP-resistant virus in breast milk and plasma, respectively. Overall, 71% (5/7) women with NVP-resistant HIV-1 in breast milk displayed >1 drug-resistant variant. Resistance in breast milk was higher at week 6 (6/13 samples [46%]) compared with week 12 (1/6 samples [17%]). In total, 10 drug-resistant populations harbouring the K103N and/or Y181C mutation were detected in the 19 breast milk samples; 7 (70%) were caused by resistant minorities (< 5% of the total HIV-1 population). In the four women with drug-resistant virus in both plasma and breast milk, the mutation patterns differed between the two compartments. Minor populations of drug-resistant HIV-1 were frequently found in breast milk of Ugandan women after exposure to NVP-SD. Further studies need to explore the role of minor drug-resistant variants in the postnatal transmission of (resistant) HIV-1.

  9. Comparison of the Abbott m2000 HIV-1 Real-Time and Roche AMPLICOR Monitor v1.5 HIV-1 assays on plasma specimens from Rakai, Uganda.

    Science.gov (United States)

    Ssebugenyi, I; Kizza, A; Mpoza, B; Aluma, G; Boaz, I; Newell, K; Laeyendecker, O; Shott, J P; Serwadda, D; Reynolds, S J

    2011-07-01

    The need for viral load (VL) monitoring of HIV patients receiving antiretroviral therapy (ART) in resource-limited settings (RLS) has become apparent with studies showing the limitations of immunological monitoring. We compared the Abbott m2000 Real-Time (Abbott) HIV-1 assay with the Roche AMPLICOR Monitor v1.5 (Roche) HIV-1 assay over a range of VL concentrations. Three hundred and eleven plasma samples were tested, including 164 samples from patients on ART ≥ six months and 147 from ART-naïve patients. The Roche assay detected ≥400 copies/mL in 158 (50.8%) samples. Of these, Abbott produced 145 (91.8%) detectable results ≥400 copies/mL; 13 (8.2%) samples produced discrepant results. Concordance between the assays for detecting HIV-1 RNA ≥400 copies/mL was 95.8% (298/311). The sensitivity, specificity, positive predictive value and negative predictive value of Abbott to detect HIV-1 RNA ≥400 copies/mL were 91.8%, 100%, 100% and 92.2%, respectively. For the 151 samples with HIV-1 RNA ≥400 copies/mL for both assays, a good linear correlation was found (r = 0.81, P Abbott assay performed well in our setting, offering an alternative methodology for HIV-1 VL for laboratories with realtime polymerase chain reaction (PCR) capacity.

  10. Introduction of HIV type 1 into an isolated population

    DEFF Research Database (Denmark)

    Madsen, Tina V; Leitner, Thomas; Lohse, Nicolai

    2007-01-01

    Introduction of HIV-1 into a population may not always give rise to a subsequent epidemic. Greenland is an isolated and sparsely populated island in The Danish Kingdom. We aimed to estimate the number of introductions of HIV-1 into Greenland, the number of subsequent epidemics, and the countries...... from which the virus was introduced. Phylogenetic analyses were performed on three regions of HIV-1 (gag, pol, and env) in samples from 70 Greenlandic patients. Furthermore, we included gene sequences from contemporary Danish HIV-1-infected patients and sequences from the Los Alamos HIV Sequence...... Database. All Greenlandic sequences were subtype B except one sequence found to be a recombinant (probably CRF13). Sequence clusters in the phylogenetic trees indicated that there had been at least nine introductions of HIV-1 into Greenland. One cluster, supported by bootstrap values of 81, 76, and 96...

  11. Bacterial vaginosis, alterations in vaginal flora and HIV genital shedding among HIV-1-infected women in Mozambique

    Directory of Open Access Journals (Sweden)

    Robert D Kirkcaldy

    2011-05-01

    Full Text Available Objectives. We investigated whether abnormal vaginal flora, including bacterial vaginosis (BV, are associated with detection of cervical HIV-1 RNA among HIV-infected women in Mozambique. Methods. We obtained clinical data and vaginal specimens from HIV-infected women registering for their first visit at one of two HIV care clinics in Mozambique. We compared women with detectable cervical HIV viral load (≥40 copies/ml with women with undetectable cervical HIV. Results. We enrolled 106 women. Women with abnormal vaginal flora (intermediate Nugent scores, 4 - 6 were more likely to have detectable cervical HIV RNA then women with normal vaginal flora (adjusted odds ratio 7.2 (95% confidence interval 1.8 - 29.1, adjusted for CD4 count. Women with BV had a non-significantly higher likelihood of detectable cervical HIV than women with normal flora. Conclusions. Abnormal vaginal flora were significantly associated with cervical HIV expression. Further research is needed to confirm this relationship.

  12. Sensitive non-radioactive detection of HIV-1

    DEFF Research Database (Denmark)

    Teglbjærg, Lars Stubbe; Nielsen, C; Hansen, J E

    1992-01-01

    This report describes the use of the polymerase chain reaction (PCR) for the non-radioactive detection of HIV-1 proviral genomic sequences in HIV-1 infected cells. We have developed a sensitive assay, using three different sets of nested primers and our results show that this method is superior...... to standard PCR for the detection of HIV-1 DNA. The assay described features the use of a simple and inexpensive sample preparation technique and a non-radioactive hybridization procedure for confirmation of results. To test the suitability of the assay for clinical purposes, we tested cell samples from 76...

  13. Concerted motions in HIV-1 TAR RNA may allow access to bound state conformations: RNA dynamics from NMR residual dipolar couplings.

    Science.gov (United States)

    Al-Hashimi, Hashim M; Gosser, Yuying; Gorin, Andrey; Hu, Weidong; Majumdar, Ananya; Patel, Dinshaw J

    2002-01-11

    Ground-state dynamics in RNA is a critical precursor for structural adaptation observed ubiquitously in protein-RNA recognition. A tertiary conformational analysis of the stem-loop structural element in the transactivation response element (TAR) from human immunodeficiency virus type 1 (HIV-I) RNA is presented using recently introduced NMR methods that rely on the measurement of residual dipolar couplings (RDC) in partially oriented systems. Order matrix analysis of RDC data provides evidence for inter-helical motions that are of amplitude 46(+/-4) degrees, of random directional character, and that are executed about an average conformation with an inter-helical angle between 44 degrees and 54 degrees. The generated ensemble of TAR conformations have different organizations of functional groups responsible for interaction with the trans-activator protein Tat, including conformations similar to the previously characterized bound-state conformation. These results demonstrate the utility of RDC-NMR for simultaneously characterizing RNA tertiary dynamics and average conformation, and indicate an avenue for TAR complex formation involving tertiary structure capture. Copyright 2001 Academic Press.

  14. Characteristics of HIV-2 and HIV-1/HIV-2 Dually Seropositive Adults in West Africa Presenting for Care and Antiretroviral Therapy: The IeDEA-West Africa HIV-2 Cohort Study.

    Science.gov (United States)

    Ekouevi, Didier K; Balestre, Eric; Coffie, Patrick A; Minta, Daouda; Messou, Eugene; Sawadogo, Adrien; Minga, Albert; Sow, Papa Salif; Bissagnene, Emmanuel; Eholie, Serge P; Gottlieb, Geoffrey S; Dabis, François; Zannou, Djimon Marcel; Ahouada, Carin; Akakpo, Jocelyn; Ahomadegbé, Christelle; Bashi, Jules; Gougounon-Houéto, Alice; Azon-Kouanou, Angèle; Houngbé, Fabien; Koumakpaï, Sikiratou; Alihonou, Florence; d'Almeida, Marcelline; Hodonou, Irvine; Hounhoui, Ghislaine; Sagbo, Gracien; Tossa-Bagnan, Leïla; Adjide, Herman; Drabo, Joseph; Bognounou, René; Dienderé, Arnaud; Traore, Eliezer; Zoungrana, Lassane; Zerbo, Béatrice; Sawadogo, Adrien Bruno; Zoungrana, Jacques; Héma, Arsène; Soré, Ibrahim; Bado, Guillaume; Tapsoba, Achille; Yé, Diarra; Kouéta, Fla; Ouedraogo, Sylvie; Ouédraogo, Rasmata; Hiembo, William; Gansonré, Mady; Messou, Eugène; Gnokoro, Joachim Charles; Koné, Mamadou; Kouakou, Guillaume Martial; Bosse, Clarisse Amani; Brou, Kouakou; Assi, Achi Isidore; Chenal, Henri; Hawerlander, Denise; Soppi, Franck; Minga, Albert; Abo, Yao; Bomisso, Germain; Eholié, Serge Paul; Amego, Mensah Deborah Noelly; Andavi, Viviane; Diallo, Zelica; Ello, Frédéric; Tanon, Aristophane Koffi; Koule, Serge Olivier; Anzan, Koffi Charles; Guehi, Calixte; Aka, Edmond Addi; Issouf, Koffi Ladji; Kouakou, Jean-Claude; N'gbeche, Marie-Sylvie; Touré, Pety; Avit-Edi, Divine; Kouakou, Kouadio; Moh, Magloire; Yao, Valérie Andoblé; Folquet, Madeleine Amorissani; Dainguy, Marie-Evelyne; Kouakou, Cyrille; Méa-Assande, Véronique Tanoh; Oka-Berete, Gladys; Zobo, Nathalie; Acquah, Patrick; Kokora, Marie-Berthe; Eboua, Tanoh François; Timité-Konan, Marguerite; Ahoussou, Lucrèce Diecket; Assouan, Julie Kebé; Sami, Mabéa Flora; Kouadio, Clémence; Renner, Lorna; Goka, Bamenla; Welbeck, Jennifer; Sackey, Adziri; Owiafe, Seth Ntiri; Wejse, Christian; Silva, Zacarias José Da; Paulo, Joao; Rodrigues, Amabelia; da Silva, David; Medina, Candida; Oliviera-Souto, Ines; Ostergaard, Lars; Laursen, Alex; Sodemann, Morten; Aaby, Peter; Fomsgaard, Anders; Erikstrup, Christian; Eugen-Olsen, Jesper; Maïga, Moussa Y; Diakité, Fatoumata Fofana; Kalle, Abdoulaye; Katile, Drissa; Traore, Hamar Alassane; Minta, Daouda; Cissé, Tidiani; Dembelé, Mamadou; Doumbia, Mohammed; Fomba, Mahamadou; Kaya, Assétou Soukho; Traoré, Abdoulaye M; Traoré, Hamady; Toure, Amadou Abathina; Dicko, Fatoumata; Sylla, Mariam; Berthé, Alima; Traoré, Hadizatou Coulibaly; Koïta, Anta; Koné, Niaboula; N'diaye, Clémentine; Coulibaly, Safiatou Touré; Traoré, Mamadou; Traoré, Naïchata; Charurat, Man; Ajayi, Samuel; Dapiap, Stephen; Otu; Igbinoba, Festus; Benson, Okwara; Adebamowo, Clément; James, Jesse; Obaseki; Osakede, Philip; Olasode, John; Sow, Papa Salif; Diop, Bernard; Manga, Noël Magloire; Tine, Judicael Malick; Signate Sy, Haby; Ba, Abou; Diagne, Aida; Dior, Hélène; Faye, Malick; Gueye, Ramatoulaye Diagne; Mbaye, Aminata Diack; Patassi, Akessiwe; Kotosso, Awèrou; Kariyare, Benjamin Goilibe; Gbadamassi, Gafarou; Komi, Agbo; Mensah-Zukong, Kankoé Edem; Pakpame, Pinuwe; Lawson-Evi, Annette Koko; Atakouma, Yawo; Takassi, Elom; Djeha, Améyo; Ephoévi-Gah, Ayoko; Djibril, Sherifa El-Hadj; Dabis, François; Bissagnene, Emmanuel; Arrivé, Elise; Coffie, Patrick; Ekouevi, Didier; Jaquet, Antoine; Leroy, Valériane; Lewden, Charlotte; Sasco, Annie; Azani, Jean-Claude; Allou, Gérard; Balestre, Eric; Bohossou, Franck; Karcher, Sophie; Gonsan, Jules Mahan; Carrou, Jérôme Le; Lenaud, Séverin; Nchot, Célestin; Malateste, Karen; Yao, Amon Roseamonde; Siloué, Bertine; Clouet, Gwenaelle; Djetouan, Hugues; Doring, Alexandra; Kouakou, Adrienne; Rabourdin, Elodie; Rivenc, Jean; Anglaret, Xavier; Ba, Boubacar; Essanin, Jean Bosco; Ciaranello, Andrea; Datté, Sébastien; Desmonde, Sophie; Diby, Jean-Serge Elvis; Gottlieb, Geoffrey S; Horo, Apollinaire Gninlgninrin; Kangah, Serge N'zoré; Malvy, Denis; Meless, David; Mounkaila-Harouna, Aida; Ndondoki, Camille; Shiboski, Caroline; Thiébaut, Rodolphe; Pac-Ci; Abidjan

    2013-01-01

    HIV-2 is endemic in West Africa. There is a lack of evidence-based guidelines on the diagnosis, management and antiretroviral therapy (ART) for HIV-2 or HIV-1/HIV-2 dual infections. Because of these issues, we designed a West African collaborative cohort for HIV-2 infection within the framework of the International epidemiological Databases to Evaluate AIDS (IeDEA). We collected data on all HIV-2 and HIV-1/HIV-2 dually seropositive patients (both ARV-naive and starting ART) and followed-up in clinical centres in the IeDEA-WA network including a total of 13 clinics in five countries: Benin, Burkina-Faso Côte d'Ivoire, Mali, and Senegal, in the West Africa region. Data was merged for 1,754 patients (56% female), including 1,021 HIV-2 infected patients (551 on ART) and 733 dually seropositive for both HIV-1 and HIV 2 (463 on ART). At ART initiation, the median age of HIV-2 patients was 45.3 years, IQR: (38.3-51.7) and 42.4 years, IQR (37.0-47.3) for dually seropositive patients (p = 0.048). Overall, 16.7% of HIV-2 patients on ART had an advanced clinical stage (WHO IV or CDC-C). The median CD4 count at the ART initiation is 166 cells/mm(3), IQR (83-247) among HIV-2 infected patients and 146 cells/mm(3), IQR (55-249) among dually seropositive patients. Overall, in ART-treated patients, the CD4 count increased 126 cells/mm(3) after 24 months on ART for HIV-2 patients and 169 cells/mm(3) for dually seropositive patients. Of 551 HIV-2 patients on ART, 5.8% died and 10.2% were lost to follow-up during the median time on ART of 2.4 years, IQR (0.7-4.3). This large multi-country study of HIV-2 and HIV-1/HIV-2 dual infection in West Africa suggests that routine clinical care is less than optimal and that management and treatment of HIV-2 could be further informed by ongoing studies and randomized clinical trials in this population.

  15. Characteristics of HIV-2 and HIV-1/HIV-2 Dually Seropositive Adults in West Africa Presenting for Care and Antiretroviral Therapy: The IeDEA-West Africa HIV-2 Cohort Study.

    Directory of Open Access Journals (Sweden)

    Didier K Ekouevi

    Full Text Available HIV-2 is endemic in West Africa. There is a lack of evidence-based guidelines on the diagnosis, management and antiretroviral therapy (ART for HIV-2 or HIV-1/HIV-2 dual infections. Because of these issues, we designed a West African collaborative cohort for HIV-2 infection within the framework of the International epidemiological Databases to Evaluate AIDS (IeDEA.We collected data on all HIV-2 and HIV-1/HIV-2 dually seropositive patients (both ARV-naive and starting ART and followed-up in clinical centres in the IeDEA-WA network including a total of 13 clinics in five countries: Benin, Burkina-Faso Côte d'Ivoire, Mali, and Senegal, in the West Africa region.Data was merged for 1,754 patients (56% female, including 1,021 HIV-2 infected patients (551 on ART and 733 dually seropositive for both HIV-1 and HIV 2 (463 on ART. At ART initiation, the median age of HIV-2 patients was 45.3 years, IQR: (38.3-51.7 and 42.4 years, IQR (37.0-47.3 for dually seropositive patients (p = 0.048. Overall, 16.7% of HIV-2 patients on ART had an advanced clinical stage (WHO IV or CDC-C. The median CD4 count at the ART initiation is 166 cells/mm(3, IQR (83-247 among HIV-2 infected patients and 146 cells/mm(3, IQR (55-249 among dually seropositive patients. Overall, in ART-treated patients, the CD4 count increased 126 cells/mm(3 after 24 months on ART for HIV-2 patients and 169 cells/mm(3 for dually seropositive patients. Of 551 HIV-2 patients on ART, 5.8% died and 10.2% were lost to follow-up during the median time on ART of 2.4 years, IQR (0.7-4.3.This large multi-country study of HIV-2 and HIV-1/HIV-2 dual infection in West Africa suggests that routine clinical care is less than optimal and that management and treatment of HIV-2 could be further informed by ongoing studies and randomized clinical trials in this population.

  16. Couple Relationship Functioning as a Source or Mitigator of HIV Risk: Associations Between Relationship Quality and Sexual Risk Behavior in Peri-urban Uganda.

    Science.gov (United States)

    Ruark, Allison; Kajubi, Phoebe; Ruteikara, Sam; Green, Edward C; Hearst, Norman

    2018-04-01

    Despite evidence that a greater focus on couples could strengthen HIV prevention efforts, little health-related research has explored relationship functioning and relationship quality among couples in Africa. Using data from 162 couples (324 individuals) resident in a peri-urban Ugandan community, we assessed actor and partner effects of sexual risk behaviors on relationship quality, using psychometric measures of dyadic adjustment, sexual satisfaction, commitment, intimacy, and communication. For women and men, poor relationship quality was associated with having concurrent sexual partners and suspecting that one's partner had concurrent sexual partners (actor effects). Women's poor relationship quality was also associated with men's sexual risk behaviors (partner effects), although the inverse partner effect was not observed. These findings suggest that relationship quality is linked to HIV risk, particularly through the pathway of concurrent sexual partnerships, and that positive relationship attributes such as sexual satisfaction, intimacy, and constructive communication can help couples to avoid risk.

  17. Cocaine promotes both initiation and elongation phase of HIV-1 transcription by activating NF-κB and MSK1 and inducing selective epigenetic modifications at HIV-1 LTR

    International Nuclear Information System (INIS)

    Sahu, Geetaram; Farley, Kalamo; El-Hage, Nazira; Aiamkitsumrit, Benjamas; Fassnacht, Ryan; Kashanchi, Fatah; Ochem, Alex; Simon, Gary L.; Karn, Jonathan; Hauser, Kurt F.; Tyagi, Mudit

    2015-01-01

    Cocaine accelerates human immunodeficiency virus (HIV-1) replication by altering specific cell-signaling and epigenetic pathways. We have elucidated the underlying molecular mechanisms through which cocaine exerts its effect in myeloid cells, a major target of HIV-1 in central nervous system (CNS). We demonstrate that cocaine treatment promotes HIV-1 gene expression by activating both nuclear factor-kappa B (NF-ĸB) and mitogen- and stress-activated kinase 1 (MSK1). MSK1 subsequently catalyzes the phosphorylation of histone H3 at serine 10, and p65 subunit of NF-ĸB at 276th serine residue. These modifications enhance the interaction of NF-ĸB with P300 and promote the recruitment of the positive transcription elongation factor b (P-TEFb) to the HIV-1 LTR, supporting the development of an open/relaxed chromatin configuration, and facilitating the initiation and elongation phases of HIV-1 transcription. Results are also confirmed in primary monocyte derived macrophages (MDM). Overall, our study provides detailed insights into cocaine-driven HIV-1 transcription and replication. - Highlights: • Cocaine induces the initiation phase of HIV transcription by activating NF-ĸB. • Cocaine induced NF-ĸB phosphorylation promotes its interaction with P300. • Cocaine enhances the elongation phase of HIV transcription by stimulating MSK1. • Cocaine activated MSK1 catalyzes the phosphorylation of histone H3 at its Ser10. • Cocaine induced H3S10 phosphorylation facilitates the recruitment of P-TEFb at LTR

  18. Cocaine promotes both initiation and elongation phase of HIV-1 transcription by activating NF-κB and MSK1 and inducing selective epigenetic modifications at HIV-1 LTR

    Energy Technology Data Exchange (ETDEWEB)

    Sahu, Geetaram; Farley, Kalamo [Division of Infectious Diseases, Department of Medicine, George Washington University, Washington, DC (United States); El-Hage, Nazira [Virginia Commonwealth University, Richmond, VA (United States); Aiamkitsumrit, Benjamas; Fassnacht, Ryan [Division of Infectious Diseases, Department of Medicine, George Washington University, Washington, DC (United States); Kashanchi, Fatah [George Mason University, Manassas, VA (United States); Ochem, Alex [ICGEB, Wernher and Beit Building, Anzio Road, Observatory, 7925 Cape Town (South Africa); Simon, Gary L. [Division of Infectious Diseases, Department of Medicine, George Washington University, Washington, DC (United States); Karn, Jonathan [Case Western Reserve University, Cleveland, OH (United States); Hauser, Kurt F. [Virginia Commonwealth University, Richmond, VA (United States); Tyagi, Mudit, E-mail: tmudit@email.gwu.edu [Division of Infectious Diseases, Department of Medicine, George Washington University, Washington, DC (United States); Department of Microbiology, Immunology and Tropical Medicine, George Washington University, Washington, DC 20037 (United States)

    2015-09-15

    Cocaine accelerates human immunodeficiency virus (HIV-1) replication by altering specific cell-signaling and epigenetic pathways. We have elucidated the underlying molecular mechanisms through which cocaine exerts its effect in myeloid cells, a major target of HIV-1 in central nervous system (CNS). We demonstrate that cocaine treatment promotes HIV-1 gene expression by activating both nuclear factor-kappa B (NF-ĸB) and mitogen- and stress-activated kinase 1 (MSK1). MSK1 subsequently catalyzes the phosphorylation of histone H3 at serine 10, and p65 subunit of NF-ĸB at 276th serine residue. These modifications enhance the interaction of NF-ĸB with P300 and promote the recruitment of the positive transcription elongation factor b (P-TEFb) to the HIV-1 LTR, supporting the development of an open/relaxed chromatin configuration, and facilitating the initiation and elongation phases of HIV-1 transcription. Results are also confirmed in primary monocyte derived macrophages (MDM). Overall, our study provides detailed insights into cocaine-driven HIV-1 transcription and replication. - Highlights: • Cocaine induces the initiation phase of HIV transcription by activating NF-ĸB. • Cocaine induced NF-ĸB phosphorylation promotes its interaction with P300. • Cocaine enhances the elongation phase of HIV transcription by stimulating MSK1. • Cocaine activated MSK1 catalyzes the phosphorylation of histone H3 at its Ser10. • Cocaine induced H3S10 phosphorylation facilitates the recruitment of P-TEFb at LTR.

  19. Performance of 3 Rapid Tests for Discrimination Between HIV-1 and HIV-2 in Guinea-Bissau, West Africa

    DEFF Research Database (Denmark)

    Hønge, Bo Langhoff; Bjarnason Obinah, Magnús Pétur; Jespersen, Sanne

    2014-01-01

    As HIV-2 is intrinsically resistant to nonnucleoside reverse transcriptase inhibitors, it is mandatory to discriminate between HIV types before initiating antiretroviral treatment. Guinea-Bissau has the world's highest prevalence of HIV-2 and HIV-1/HIV-2 dually infected individuals. We evaluated ...... (agreement 90.9%) and SD Bioline HIV-1/2 3.0 (agreement 84.5%). Our results underscore the need for evaluation of tests in relevant populations before implementation....

  20. IFITM Proteins Restrict HIV-1 Infection by Antagonizing the Envelope Glycoprotein

    Directory of Open Access Journals (Sweden)

    Jingyou Yu

    2015-10-01

    Full Text Available The interferon-induced transmembrane (IFITM proteins have been recently shown to restrict HIV-1 and other viruses. Here, we provide evidence that IFITM proteins, particularly IFITM2 and IFITM3, specifically antagonize the HIV-1 envelope glycoprotein (Env, thereby inhibiting viral infection. IFITM proteins interact with HIV-1 Env in viral producer cells, leading to impaired Env processing and virion incorporation. Notably, the level of IFITM incorporation into HIV-1 virions does not strictly correlate with the extent of inhibition. Prolonged passage of HIV-1 in IFITM-expressing T lymphocytes leads to emergence of Env mutants that overcome IFITM restriction. The ability of IFITMs to inhibit cell-to-cell infection can be extended to HIV-1 primary isolates, HIV-2 and SIVs; however, the extent of inhibition appears to be virus-strain dependent. Overall, our study uncovers a mechanism by which IFITM proteins specifically antagonize HIV-1 Env to restrict HIV-1 infection and provides insight into the specialized role of IFITMs in HIV infection.

  1. HIV-1-negative female sex workers sustain high cervical IFNɛ, low immune activation, and low expression of HIV-1-required host genes.

    Science.gov (United States)

    Abdulhaqq, S A; Zorrilla, C; Kang, G; Yin, X; Tamayo, V; Seaton, K E; Joseph, J; Garced, S; Tomaras, G D; Linn, K A; Foulkes, A S; Azzoni, L; VerMilyea, M; Coutifaris, C; Kossenkov, A V; Showe, L; Kraiselburd, E N; Li, Q; Montaner, L J

    2016-07-01

    Sex workers practicing in high HIV endemic areas have been extensively targeted to test anti-HIV prophylactic strategies. We hypothesize that in women with high levels of genital exposure to semen changes in cervico-vaginal mucosal and/or systemic immune activation will contribute to a decreased susceptibility to HIV-1 infection. To address this question, we assessed sexual activity and immune activation status (in peripheral blood), as well as cellular infiltrates and gene expression in ectocervical mucosa biopsies in female sex workers (FSWs; n=50), as compared with control women (CG; n=32). FSWs had low-to-absent HIV-1-specific immune responses with significantly lower CD38 expression on circulating CD4(+) or CD8(+) T-cells (both: PHIV-1 integration and replication. A correlative relationship between semen exposure and elevated type-1 IFN expression in FSWs was also established. Overall, our data suggest that long-term condomless sex work can result in multiple changes within the cervico-vaginal compartment that would contribute to sustaining a lower susceptibility for HIV-1 infection in the absence of HIV-specific responses.

  2. Human immunodeficiency virus type-1 (HIV-1) genetic diversity and ...

    African Journals Online (AJOL)

    PROGMANAGER

    2013-04-24

    Apr 24, 2013 ... objective of this study was to determine the genetic diversity of HIV-1 and the prevalence of antiretroviral (ARV) ... individuals in resource limited settings. Key words: ... management of HIV infection even as antiretroviral (ARV).

  3. Correlation of immune activation with HIV-1 RNA levels assayed by real-time RT-PCR in HIV-1 Subtype C infected patients in Northern India

    Science.gov (United States)

    Agarwal, Atima; Sankaran, Sumathi; Vajpayee, Madhu; Sreenivas, V; Seth, Pradeep; Dandekar, Satya

    2014-01-01

    Background Assays with specificity and cost effectiveness are needed for the measurement of HIV-1 burden to monitor disease progression or response to anti-retroviral therapy (ART) in HIV-1 subtype C infected patients. Objectives The objective of this study was to develop and validate an affordable; one step Real-Time RT-PCR assay with high specificity and sensitivity to measure plasma HIV-1 loads in HIV-1 subtype C infected patients. Results We developed an RT-PCR assay to detect and quantitate plasma HIV-1 levels in HIV-1 subtype C infected patients. An inverse correlation between plasma viral loads (PVL) and CD4+ T-cell numbers was detected at all CDC stages. Significant correlations were found between CD8+ T-cell activation and PVL, as well as with the clinical and immunological status of the patients. Conclusions The RT-PCR assay provides a sensitive method to measure PVL in HIV-1 subtype C infected patients. Viral loads correlated with immune activation and can be used to monitor HIV care in India. PMID:17962068

  4. HIV-1, Methamphetamine and Astrocytes at Neuroinflammatory crossroads

    Directory of Open Access Journals (Sweden)

    Kathleen eBorgmann

    2015-10-01

    Full Text Available As a popular psychostimulant, methamphetamine (METH use leads to long-lasting, strong euphoric effects. While METH abuse is common in the general population, between 10-15% of human immunodeficiency virus-1 (HIV-1 patients report having abused METH. METH exacerbates the severity and onset of HIV-1-associated neurocognitive disorders (HAND through direct and indirect mechanisms. Repetitive METH use decreases adherence to antiretroviral drug regimens, increasing the likelihood of HIV-1 disease progression towards AIDS. METH exposure also directly affects both innate and adaptive immunity, altering lymphocyte number and activity, cytokine signaling, phagocytic function, and CNS infiltration through the blood brain barrier. Further, METH triggers the neuronal dopamine reward pathway and leads to altered neuronal activity and direct toxicity. Concurrently, METH and HIV-1 alter the neuroimmune balance and induce neuroinflammation. Neuroinflammation modulates a wide range of brain functions including neuronal signaling and activity, glial activation, viral infection, oxidative stress and excitotoxicity. Pathologically, glial activation is a hallmark of both HIV-1 and METH-associated neuroinflammation. Significant commonality exists in the neurotoxic mechanisms for both METH and HAND; however, the pathways dysregulated in astroglia during METH exposure are less clear. Thus alterations in astrocyte intracellular signaling pathways, gene expression and function during METH and HIV-1 comorbidity, neuroinflammation and HAND are carefully reviewed. Interventions targeting astrocytes in HAND and METH are presented as potential novel therapeutic approaches.

  5. Interferon-Inducible CD169/Siglec1 Attenuates Anti-HIV-1 Effects of Alpha Interferon

    Science.gov (United States)

    Akiyama, Hisashi; Ramirez, Nora-Guadalupe Pina; Gibson, Gregory; Kline, Christopher; Watkins, Simon; Ambrose, Zandrea

    2017-01-01

    ABSTRACT A hallmark of human immunodeficiency virus type 1 (HIV-1) infection in vivo is chronic immune activation concomitant with type I interferon (IFN) production. Although type I IFN induces an antiviral state in many cell types, HIV-1 can replicate in vivo via mechanisms that have remained unclear. We have recently identified a type I IFN-inducible protein, CD169, as the HIV-1 attachment factor on dendritic cells (DCs) that can mediate robust infection of CD4+ T cells in trans. Since CD169 expression on macrophages is also induced by type I IFN, we hypothesized that type I IFN-inducible CD169 could facilitate productive HIV-1 infection in myeloid cells in cis and CD4+ T cells in trans and thus offset antiviral effects of type I IFN. In support of this hypothesis, infection of HIV-1 or murine leukemia virus Env (MLV-Env)-pseudotyped HIV-1 particles was enhanced in IFN-α-treated THP-1 monocytoid cells, and this enhancement was primarily dependent on CD169-mediated enhancement at the virus entry step, a phenomenon phenocopied in HIV-1 infections of IFN-α-treated primary monocyte-derived macrophages (MDMs). Furthermore, expression of CD169, a marker of type I IFN-induced immune activation in vivo, was enhanced in lymph nodes from pigtailed macaques infected with simian immunodeficiency virus (SIV) carrying HIV-1 reverse transcriptase (RT-SHIV), compared to uninfected macaques, and interestingly, there was extensive colocalization of p27gag and CD169, suggesting productive infection of CD169+ myeloid cells in vivo. While cell-free HIV-1 infection of IFN-α-treated CD4+ T cells was robustly decreased, initiation of infection in trans via coculture with CD169+ IFN-α-treated DCs restored infection, suggesting that HIV-1 exploits CD169 in cis and in trans to attenuate a type I IFN-induced antiviral state. IMPORTANCE HIV-1 infection in humans causes immune activation characterized by elevated levels of proinflammatory cytokines, including type I interferons (IFN

  6. Profile of the HIV epidemic in Cape Verde: molecular epidemiology and drug resistance mutations among HIV-1 and HIV-2 infected patients from distinct islands of the archipelago.

    Science.gov (United States)

    de Pina-Araujo, Isabel Inês M; Guimarães, Monick L; Bello, Gonzalo; Vicente, Ana Carolina P; Morgado, Mariza G

    2014-01-01

    HIV-1 and HIV-2 have been detected in Cape Verde since 1987, but little is known regarding the genetic diversity of these viruses in this archipelago, located near the West African coast. In this study, we characterized the molecular epidemiology of HIV-1 and HIV-2 and described the occurrence of drug resistance mutations (DRM) among antiretroviral therapy naïve (ARTn) patients and patients under treatment (ARTexp) from different Cape Verde islands. Blood samples, socio-demographic and clinical-laboratory data were obtained from 221 HIV-positive individuals during 2010-2011. Phylogenetic and bootscan analyses of the pol region (1300 bp) were performed for viral subtyping. HIV-1 and HIV-2 DRM were evaluated for ARTn and ARTexp patients using the Stanford HIV Database and HIV-GRADE e.V. Algorithm Homepage, respectively. Among the 221 patients (169 [76.5%] HIV-1, 43 [19.5%] HIV-2 and 9 [4.1%] HIV-1/HIV-2 co-infections), 67% were female. The median ages were 34 (IQR = 1-75) and 47 (IQR = 12-84) for HIV-1 and HIV-2, respectively. HIV-1 infections were due to subtypes G (36.6%), CRF02_AG (30.6%), F1 (9.7%), URFs (10.4%), B (5.2%), CRF05_DF (3.0%), C (2.2%), CRF06_cpx (0.7%), CRF25_cpx (0.7%) and CRF49_cpx (0.7%), whereas all HIV-2 infections belonged to group A. Transmitted DRM (TDRM) was observed in 3.4% (2/58) of ARTn HIV-1-infected patients (1.7% NRTI, 1.7% NNRTI), but not among those with HIV-2. Among ARTexp patients, DRM was observed in 47.8% (33/69) of HIV-1 (37.7% NRTI, 37.7% NNRTI, 7.4% PI, 33.3% for two classes) and 17.6% (3/17) of HIV-2-infections (17.6% NRTI, 11.8% PI, 11.8% both). This study indicates that Cape Verde has a complex and unique HIV-1 molecular epidemiological scenario dominated by HIV-1 subtypes G, CRF02_AG and F1 and HIV-2 subtype A. The occurrence of TDRM and the relatively high level of DRM among treated patients are of concern. Continuous monitoring of patients on ART, including genotyping, are public policies to be implemented.

  7. Six Highly Conserved Targets of RNAi Revealed in HIV-1-Infected Patients from Russia Are Also Present in Many HIV-1 Strains Worldwide

    Directory of Open Access Journals (Sweden)

    Olga V. Kretova

    2017-09-01

    Full Text Available RNAi has been suggested for use in gene therapy of HIV/AIDS, but the main problem is that HIV-1 is highly variable and could escape attack from the small interfering RNAs (siRNAs due to even single nucleotide substitutions in the potential targets. To exhaustively check the variability in selected RNA targets of HIV-1, we used ultra-deep sequencing of six regions of HIV-1 from the plasma of two independent cohorts of patients from Russia. Six RNAi targets were found that are invariable in 82%–97% of viruses in both cohorts and are located inside the domains specifying reverse transcriptase (RT, integrase, vpu, gp120, and p17. The analysis of mutation frequencies and their characteristics inside the targets suggests a likely role for APOBEC3G (apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like 3G, A3G in G-to-A mutations and a predominant effect of RT biases in the detected variability of the virus. The lowest frequency of mutations was detected in the central part of all six targets. We also discovered that the identical RNAi targets are present in many HIV-1 strains from many countries and from all continents. The data are important for both the understanding of the patterns of HIV-1 mutability and properties of RT and for the development of gene therapy approaches using RNAi for the treatment of HIV/AIDS. Keywords: HIV-1, RNAi targets, gene therapy, ultra-deep sequencing, conserved HIV-1 sequences

  8. Cocaine promotes both initiation and elongation phase of HIV-1 transcription by activating NF-κB and MSK1 and inducing selective epigenetic modifications at HIV-1 LTR

    Science.gov (United States)

    Sahu, Geetaram; Farley, Kalamo; El-Hage, Nazira; Aiamkitsumrit, Benjamas; Fassnacht, Ryan; Kashanchi, Fatah; Ochem, Alex; Simon, Gary L.; Karn, Jonathan; Hauser, Kurt F.; Tyagi, Mudit

    2015-01-01

    Cocaine accelerates human immunodeficiency virus (HIV-1) replication by altering specific cell-signaling and epigenetic pathways. We have elucidated the underlying molecular mechanisms through which cocaine exerts its effect in myeloid cells, a major target of HIV-1 in central nervous system (CNS). We demonstrate that cocaine treatment promotes HIV-1 gene expression by activating both nuclear factor-kappa B (NF-κB) and mitogen- and stress-activated kinase 1 (MSK1). MSK1 subsequently catalyzes the phosphorylation of histone H3 at serine 10, and p65 subunit of NF-κB at 276th serine residue. These modifications enhance the interaction of NF-κB with P300 and promote the recruitment of the positive transcription elongation factor b (P-TEFb) to the HIV-1 LTR, supporting the development of an open/relaxed chromatin configuration, and facilitating the initiation and elongation phases of HIV-1 transcription. Results are also confirmed in primary monocyte derived macrophages (MDM). Overall, our study provides detailed insights into cocaine-driven HIV-1 transcription and replication. PMID:25980739

  9. Sero- and Molecular Epidemiology of HIV-1 in Papua Province, Indonesia

    Directory of Open Access Journals (Sweden)

    Muhammad Qushai Yunifiar M

    2017-11-01

    Full Text Available Background: human immunodeficiency virus (HIV infection and acquired immune deficiency syndrome (AIDS cause serious health problems and affect the Indonesian economy. Papua province has the highest prevalence of HIV infection in the country; however, epidemiological data are limited. Therefore, in order to reveal the current situation of HIV/AIDS in Papua province, sero- and molecular epidemiological studies of HIV were conducted. Methods: serological tests were conducted on 157 healthy individuals from the general population residing in Paniai, Papua. In addition, a molecular epidemiological study was then conducted on HIV type 1 (HIV-1 genes derived from infected individuals. Peripheral blood samples from HIV-1-positive individuals and 15 additionally enrolled, previously confirmed HIV-1-positive individuals were subjected to a genotypic analysis. Results: serological tests revealed that 2 out of 157 (1.27% healthy individuals were HIV-positive. In addition, HIV-1 subtyping revealed that subtype B and CRF01_AE were the major subtype and circulating recombinant form (CRF of HIV-1 prevalent in the region, while subtype A1 and a recombinant form including viral gene fragments of CRF01_AE and subtype B was also detected. In addition, HIV drug resistance-associated major mutations were detected in the reverse transcriptase gene derived from infected individual on antiretroviral therapy. Conclusion: these results provide important information for clearer understanding on the current situation of HIV/AIDS in Papua province in Indonesia.

  10. SAMHD1 controls cell cycle status, apoptosis and HIV-1 infection in monocytic THP-1 cells

    International Nuclear Information System (INIS)

    Bonifati, Serena; Daly, Michele B.; St Gelais, Corine; Kim, Sun Hee; Hollenbaugh, Joseph A.; Shepard, Caitlin; Kennedy, Edward M.; Kim, Dong-Hyun; Schinazi, Raymond F.; Kim, Baek; Wu, Li

    2016-01-01

    SAMHD1 limits HIV-1 infection in non-dividing myeloid cells by decreasing intracellular dNTP pools. HIV-1 restriction by SAMHD1 in these cells likely prevents activation of antiviral immune responses and modulates viral pathogenesis, thus highlighting a critical role of SAMHD1 in HIV-1 physiopathology. Here, we explored the function of SAMHD1 in regulating cell proliferation, cell cycle progression and apoptosis in monocytic THP-1 cells. Using the CRISPR/Cas9 technology, we generated THP-1 cells with stable SAMHD1 knockout. We found that silencing of SAMHD1 in cycling cells stimulates cell proliferation, redistributes cell cycle population in the G_1/G_0 phase and reduces apoptosis. These alterations correlated with increased dNTP levels and more efficient HIV-1 infection in dividing SAMHD1 knockout cells relative to control. Our results suggest that SAMHD1, through its dNTPase activity, affects cell proliferation, cell cycle distribution and apoptosis, and emphasize a key role of SAMHD1 in the interplay between cell cycle regulation and HIV-1 infection.

  11. SAMHD1 controls cell cycle status, apoptosis and HIV-1 infection in monocytic THP-1 cells

    Energy Technology Data Exchange (ETDEWEB)

    Bonifati, Serena [Center for Retrovirus Research, Department of Veterinary Biosciences, The Ohio State University, Columbus, OH (United States); Daly, Michele B. [Center for Drug Discovery, Department of Pediatrics, School of Medicine, Emory University, Atlanta, GA (United States); St Gelais, Corine; Kim, Sun Hee [Center for Retrovirus Research, Department of Veterinary Biosciences, The Ohio State University, Columbus, OH (United States); Hollenbaugh, Joseph A.; Shepard, Caitlin [Center for Drug Discovery, Department of Pediatrics, School of Medicine, Emory University, Atlanta, GA (United States); Kennedy, Edward M. [Department of Molecular Genetics and Microbiology, Duke University, Durham, NC (United States); Kim, Dong-Hyun [Department of Pharmacy, School of Pharmacy, Kyung-Hee University, Seoul (Korea, Republic of); Schinazi, Raymond F. [Center for Drug Discovery, Department of Pediatrics, School of Medicine, Emory University, Atlanta, GA (United States); Kim, Baek, E-mail: baek.kim@emory.edu [Center for Drug Discovery, Department of Pediatrics, School of Medicine, Emory University, Atlanta, GA (United States); Department of Pharmacy, School of Pharmacy, Kyung-Hee University, Seoul (Korea, Republic of); Wu, Li, E-mail: wu.840@osu.edu [Center for Retrovirus Research, Department of Veterinary Biosciences, The Ohio State University, Columbus, OH (United States)

    2016-08-15

    SAMHD1 limits HIV-1 infection in non-dividing myeloid cells by decreasing intracellular dNTP pools. HIV-1 restriction by SAMHD1 in these cells likely prevents activation of antiviral immune responses and modulates viral pathogenesis, thus highlighting a critical role of SAMHD1 in HIV-1 physiopathology. Here, we explored the function of SAMHD1 in regulating cell proliferation, cell cycle progression and apoptosis in monocytic THP-1 cells. Using the CRISPR/Cas9 technology, we generated THP-1 cells with stable SAMHD1 knockout. We found that silencing of SAMHD1 in cycling cells stimulates cell proliferation, redistributes cell cycle population in the G{sub 1}/G{sub 0} phase and reduces apoptosis. These alterations correlated with increased dNTP levels and more efficient HIV-1 infection in dividing SAMHD1 knockout cells relative to control. Our results suggest that SAMHD1, through its dNTPase activity, affects cell proliferation, cell cycle distribution and apoptosis, and emphasize a key role of SAMHD1 in the interplay between cell cycle regulation and HIV-1 infection.

  12. Molecular Mechanisms in Activation of Latent HIV-1

    NARCIS (Netherlands)

    H. Rafati (Haleh)

    2014-01-01

    markdownabstract__Abstract__ Finding a cure for the human immunodeficiency virus type 1 (HIV-1) is extremely challenging. Development of highly active anti-retroviral therapy (HAART), transformed HIV-1 infection from an acute syndrome into chronic disease. Although using HAART results in

  13. Identification of dual-tropic HIV-1 using evolved neural networks.

    Science.gov (United States)

    Fogel, Gary B; Lamers, Susanna L; Liu, Enoch S; Salemi, Marco; McGrath, Michael S

    2015-11-01

    Blocking the binding of the envelope HIV-1 protein to immune cells is a popular concept for development of anti-HIV therapeutics. R5 HIV-1 binds CCR5, X4 HIV-1 binds CXCR4, and dual-tropic HIV-1 can bind either coreceptor for cellular entry. R5 viruses are associated with early infection and over time can evolve to X4 viruses that are associated with immune failure. Dual-tropic HIV-1 is less studied; however, it represents functional antigenic intermediates during the transition of R5 to X4 viruses. Viral tropism is linked partly to the HIV-1 envelope V3 domain, where the amino acid sequence helps dictate the receptor a particular virus will target; however, using V3 sequence information to identify dual-tropic HIV-1 isolates has remained difficult. Our goal in this study was to elucidate features of dual-tropic HIV-1 isolates that assist in the biological understanding of dual-tropism and develop an approach for their detection. Over 1559 HIV-1 subtype B sequences with known tropisms were analyzed. Each sequence was represented by 73 structural, biochemical and regional features. These features were provided to an evolved neural network classifier and evaluated using balanced and unbalanced data sets. The study resolved R5X4 viruses from R5 with an accuracy of 81.8% and from X4 with an accuracy of 78.8%. The approach also identified a set of V3 features (hydrophobicity, structural and polarity) that are associated with tropism transitions. The ability to distinguish R5X4 isolates will improve computational tropism decisions for R5 vs. X4 and assist in HIV-1 research and drug development efforts. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  14. Analysis of Select Herpes Simplex Virus 1 (HSV-1) Proteins for Restriction of Human Immunodeficiency Virus Type 1 (HIV-1): HSV-1 gM Protein Potently Restricts HIV-1 by Preventing Intracellular Transport and Processing of Env gp160.

    Science.gov (United States)

    Polpitiya Arachchige, Sachith; Henke, Wyatt; Pramanik, Ankita; Kalamvoki, Maria; Stephens, Edward B

    2018-01-15

    Virus-encoded proteins that impair or shut down specific host cell functions during replication can be used as probes to identify potential proteins/pathways used in the replication of viruses from other families. We screened nine proteins from herpes simplex virus 1 (HSV-1) for the ability to enhance or restrict human immunodeficiency virus type 1 (HIV-1) replication. We show that several HSV-1 proteins (glycoprotein M [gM], US3, and UL24) potently restricted the replication of HIV-1. Unlike UL24 and US3, which reduced viral protein synthesis, we observed that gM restriction of HIV-1 occurred through interference with the processing and transport of gp160, resulting in a significantly reduced level of mature gp120/gp41 released from cells. Finally, we show that an HSV-1 gM mutant lacking the majority of the C-terminal domain (HA-gM[Δ345-473]) restricted neither gp160 processing nor the release of infectious virus. These studies identify proteins from heterologous viruses that can restrict viruses through novel pathways. IMPORTANCE HIV-1 infection of humans results in AIDS, characterized by the loss of CD4 + T cells and increased susceptibility to opportunistic infections. Both HIV-1 and HSV-1 can infect astrocytes and microglia of the central nervous system (CNS). Thus, the identification of HSV-1 proteins that directly restrict HIV-1 or interfere with pathways required for HIV-1 replication could lead to novel antiretroviral strategies. The results of this study show that select viral proteins from HSV-1 can potently restrict HIV-1. Further, our results indicate that the gM protein of HSV-1 restricts HIV-1 through a novel pathway by interfering with the processing of gp160 and its incorporation into virus maturing from the cell. Copyright © 2018 American Society for Microbiology.

  15. Regional gene expression of LOX-1, VCAM-1, and ICAM-1 in aorta of HIV-1 transgenic rats

    DEFF Research Database (Denmark)

    Hag, Anne Mette Fisker; Kristoffersen, Ulrik Sloth; Pedersen, Sune Folke

    2009-01-01

    endpoints, studies in animal models could be attractive alternatives. METHODOLOGY/PRINCIPAL FINDINGS: We evaluated gene expression of lectin-like oxidized-low-density-lipoprotein receptor-1 (LOX-1), vascular cell adhesion molecule-1 (VCAM-1), and intercellular adhesion molecule-1 (ICAM-1) in HIV-1...... transgenic (HIV-1Tg) rats; these genes are all thought to play important roles in early atherogenesis. Furthermore, the plasma level of sICAM-1 was measured. We found that gene expressions of LOX-1 and VCAM-1 were higher in the aortic arch of HIV-1Tg rats compared to controls. Also, the level of sICAM-1......-infection per se may cause atherosclerosis. This transgenic rat model may be a very promising model for further studies of the pathophysiology behind HIV-associated cardiovascular disease....

  16. Striking HIV-1 Entry by Targeting HIV-1 gp41. But, Where Should We Target?

    Directory of Open Access Journals (Sweden)

    Cátia Teixeira

    Full Text Available HIV-1 gp41 facilitates the viral fusion through a conformational switch involving the association of three C-terminal helices along the conserved hydrophobic grooves of three N-terminal helices coiled-coil. The control of these structural rearrangements is thought to be central to HIV-1 entry and, therefore, different strategies of intervention are being developed. Herewith, we describe a procedure to simulate the folding of an HIV-1 gp41 simplified model. This procedure is based on the construction of plausible conformational pathways, which describe protein transition between non-fusogenic and fusogenic conformations. The calculation of the paths started with 100 molecular dynamics simulations of the non-fusogenic conformation, which were found to converge to different intermediate states. Those presenting defined criteria were selected for separate targeted molecular dynamics simulations, subjected to a force constant imposing a movement towards the gp41 fusogenic conformation. Despite significant diversity, a preferred sequence of events emerged when the simulations were analyzed in terms of the formation, breakage and evolution of the contacts. We pointed out 29 residues as the most relevant for the movement of gp41; also, 2696 possible interactions were reduced to only 48 major interactions, which reveals the efficiency of the method. The analysis of the evolution of the main interactions lead to the detection of four main behaviors for those contacts: stable, increasing, decreasing and repulsive interactions. Altogether, these results suggest a specific small cavity of the HIV-1 gp41 hydrophobic groove as the preferred target to small molecules.

  17. Necroptosis takes place in human immunodeficiency virus type-1 (HIV-1-infected CD4+ T lymphocytes.

    Directory of Open Access Journals (Sweden)

    Ting Pan

    Full Text Available Human immunodeficiency virus type 1 (HIV-1 infection is characterized by progressive depletion of CD4+ T lymphocytes and dysfunction of the immune system. The numbers of CD4+ T lymphocytes in the human body are maintained constantly by homeostatic mechanisms that failed during HIV-1 infection, resulting in progressive loss of CD4+ T cells mainly via apoptosis. Recently, a non-apoptotic form of necrotic programmed cell death, named necroptosis, has been investigated in many biological and pathological processes. We then determine whether HIV-1-infected cells also undergo necroptosis. In this report, we demonstrate that HIV-1 not only induces apoptosis, but also mediates necroptosis in the infected primary CD4+ T lymphocytes and CD4+ T-cell lines. Necroptosis-dependent cytopathic effects are significantly increased in HIV-1-infected Jurkat cells that is lack of Fas-associated protein-containing death domain (FADD, indicating that necroptosis occurs as an alternative cell death mechanism in the absence of apoptosis. Unlike apoptosis, necroptosis mainly occurs in HIV-infected cells and spares bystander damage. Treatment with necrostatin-1(Nec-1, a RIP1 inhibitor that specifically blocks the necroptosis pathway, potently restrains HIV-1-induced cytopathic effect and interestingly, inhibits the formation of HIV-induced syncytia in CD4+ T-cell lines. This suggests that syncytia formation is mediated, at least partially, by necroptosis-related processes. Furthermore, we also found that the HIV-1 infection-augmented tumor necrosis factor-alpha (TNF-α plays a key role in inducing necroptosis and HIV-1 Envelope and Tat proteins function as its co-factors. Taken together,necroptosis can function as an alternative cell death pathway in lieu of apoptosis during HIV-1 infection, thereby also contributing to HIV-1-induced cytopathic effects. Our results reveal that in addition to apoptosis, necroptosis also plays an important role in HIV-1-induced pathogenesis.

  18. Schistosomiasis and HIV-1 infection in rural Zimbabwe

    DEFF Research Database (Denmark)

    Kallestrup, Per; Zinyama, Rutendo; Gomo, Exnevia

    2005-01-01

    Stunted development and reduced fecundity of Schistosoma parasites in immunodeficient mice and the impaired ability of human immunodeficiency virus 1 (HIV-1)-infected humans to excrete schistosome eggs have been described. This study explores the effect that HIV-1-associated immunodeficiency has...

  19. Factors Associated with Delayed Enrollment in HIV Medical Care among HIV-Positive Individuals in Odessa Region, Ukraine.

    Science.gov (United States)

    Neduzhko, Oleksandr; Postnov, Oleksandr; Perehinets, Ihor; DeHovitz, Jack; Joseph, Michael; Odegaard, David; Kaplan, Robert; Kiriazova, Tetiana

    In Ukraine, about one-third of identified HIV-positive individuals are not connected to care. We conducted a cross-sectional survey (n = 200) among patients registered at Odessa AIDS centers in October to December 2011. Factors associated with delayed enrollment in HIV care (>3 months since positive HIV test) were evaluated using logistic regression. Among study participants (mean age 35 ± 8.2 years, 47.5% female, 42.5% reported history of injecting drugs), 55% delayed HIV care enrollment. Odds of delayed enrollment were higher for those with lower educational attainment (adjusted odds ratio [aOR]: 2.65, 95% confidence interval [CI]: 1.04-6.76), not feeling ill (aOR: 2.98, 95% CI: 1.50-5.93), or not having time to go to the AIDS center (aOR: 3.89, 95% CI: 1.39-10.89); injection drug use was not associated with delayed enrollment. Programs linking HIV-positive individuals to specialized care should address enrollment barriers and include education on HIV care benefits and case management for direct linkage to care. HIV testing and treatment should be coupled to ensure a continuum of care.

  20. Mortality Attributable to Smoking Among HIV-1-Infected Individuals

    DEFF Research Database (Denmark)

    Helleberg, Marie; Afzal, Shoaib; Kronborg, Gitte

    2013-01-01

    and with HIV among current and nonsmoking individuals from a population-based, nationwide HIV cohort and a cohort of matched HIV-negative individuals.Results. A total of 2921 HIV patients and 10 642 controls were followed for 14 281 and 45 122 person-years, respectively. All-cause and non......-AIDS-related mortality was substantially increased among smoking compared to nonsmoking HIV patients (MRR, 4.4 [95% confidence interval {CI}, 3.0-6.7] and 5.3 [95% CI, 3.2-8.8], respectively). Excess MR per 1000 person-years among current vs nonsmokers was 17.6 (95% CI, 13.3-21.9) for HIV patients and 4.8 (95% CI, 3.......2-6.4) for controls. A 35-year-old HIV patient had a median life expectancy of 62.6 years (95% CI, 59.9-64.6) for smokers and 78.4 years (95% CI, 70.8-84.0) for nonsmokers; the numbers of life-years lost in association with smoking and HIV were 12.3 (95% CI, 8.1-16.4) and 5.1 (95% CI, 1.6-8.5). The population...

  1. Phylodynamics of the HIV-1 epidemic in Cuba.

    Science.gov (United States)

    Delatorre, Edson; Bello, Gonzalo

    2013-01-01

    Previous studies have shown that the HIV-1 epidemic in Cuba displayed a complex molecular epidemiologic profile with circulation of several subtypes and circulating recombinant forms (CRF); but the evolutionary and population history of those viral variants remains unknown. HIV-1 pol sequences of the most prevalent Cuban lineages (subtypes B, C and G, CRF18_cpx, CRF19_cpx, and CRFs20/23/24_BG) isolated between 1999 and 2011 were analyzed. Maximum-likelihood analyses revealed multiple introductions of subtype B (n≥66), subtype C (n≥10), subtype G (n≥8) and CRF18_cpx (n≥2) viruses in Cuba. The bulk of HIV-1 infections in this country, however, was caused by dissemination of a few founder strains probably introduced from North America/Europe (clades B(CU-I) and B(CU-II)), east Africa (clade C(CU-I)) and central Africa (clades G(CU), CRF18(CU) and CRF19(CU)), or locally generated (clades CRFs20/23/24_BG). Bayesian-coalescent analyses show that the major HIV-1 founder strains were introduced into Cuba during 1985-1995; whereas the CRFs_BG strains emerged in the second half of the 1990s. Most HIV-1 Cuban clades appear to have experienced an initial period of fast exponential spread during the 1990s and early 2000s, followed by a more recent decline in growth rate. The median initial growth rate of HIV-1 Cuban clades ranged from 0.4 year⁻¹ to 1.6 year⁻¹. Thus, the HIV-1 epidemic in Cuba has been a result of the successful introduction of a few viral strains that began to circulate at a rather late time of the AIDS pandemic, but then were rapidly disseminated through local transmission networks.

  2. Imperatorin inhibits HIV-1 replication through an Sp1-dependent pathway.

    Science.gov (United States)

    Sancho, Rocío; Márquez, Nieves; Gómez-Gonzalo, Marta; Calzado, Marco A; Bettoni, Giorgio; Coiras, Maria Teresa; Alcamí, José; López-Cabrera, Manuel; Appendino, Giovanni; Muñoz, Eduardo

    2004-09-03

    Coumarins and structurally related compounds have been recently shown to present anti-human immunodeficiency virus, type 1 (HIV-1) activity. Among them, the dietary furanocoumarin imperatorin is present in citrus fruits, in culinary herbs, and in some medicinal plants. In this study we report that imperatorin inhibits either vesicular stomatitis virus-pseudotyped or gp160-enveloped recombinant HIV-1 infection in several T cell lines and in HeLa cells. These recombinant viruses express luciferase as a marker of viral replication. Imperatorin did not inhibit the reverse transcription nor the integration steps in the viral cell cycle. Using several 5' long terminal repeat-HIV-1 constructs where critical response elements were either deleted or mutated, we found that the transcription factor Sp1 is critical for the inhibitory activity of imperatorin induced by both phorbol 12-myristate 13-acetate and HIV-1 Tat. Moreover in transient transfections imperatorin specifically inhibited phorbol 12-myristate 13-acetate-induced transcriptional activity of the Gal4-Sp1 fusion protein. Since Sp1 is also implicated in cell cycle progression we further studied the effect of imperatorin on cyclin D1 gene transcription and protein expression and in HeLa cell cycle progression. We found that imperatorin strongly inhibited cyclin D1 expression and arrested the cells at the G(1) phase of the cell cycle. These results highlight the potential of Sp1 transcription factor as a target for natural anti-HIV-1 compounds such as furanocoumarins that might have a potential therapeutic role in the management of AIDS.

  3. Inefficient HIV-1 trans infection of CD4+ T cells by macrophages from HIV-1 nonprogressors is associated with altered membrane cholesterol and DC-SIGN.

    Science.gov (United States)

    DeLucia, Diana C; Rinaldo, Charles R; Rappocciolo, Giovanna

    2018-04-11

    Professional antigen presenting cells (APC: myeloid dendritic cells (DC) and macrophages (MΦ); B lymphocytes) mediate highly efficient HIV-1 infection of CD4 + T cells, termed trans infection, that could contribute to HIV-1 pathogenesis. We have previously shown that lower cholesterol content in DC and B lymphocytes is associated with a lack of HIV-1 trans infection in HIV-1 infected nonprogressors (NP). Here we assessed whether HIV-1 trans infection mediated by another major APC, MΦ, is deficient in NP due to altered cholesterol metabolism. When comparing healthy HIV-1 seronegatives (SN), rapid progressors (PR), and NP, we found that monocyte-derived MΦ from NP did not mediate HIV-1 trans infection of autologous CD4 + T cells, in contrast to efficient trans infection mediated by SN and PR MΦ. MΦ trans infection efficiency was directly associated with the number of DC-specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN)-expressing MΦ. Significantly fewer NP MΦ expressed DC-SIGN. Unesterified (free) cholesterol in MΦ cell membranes and lipid rafting was significantly lower in NP than PR, as well as virus internalization in early endosomes. Furthermore, simvastatin (SIMV), decreased the subpopulation of DC-SIGN + MΦ, as well as MΦ cis and trans infection. Notably, SIMV decreased cell membrane cholesterol and led to lipid raft dissociation, effectively mimicking the incompetent APC trans infection environment characteristic of NP. Our data support that DC-SIGN and membrane cholesterol are central to MΦ trans infection, and a lack of these limits HIV-1 disease progression. Targeting the ability of MΦ to drive HIV-1 dissemination in trans could enhance HIV-1 therapeutic strategies. IMPORTANCE Despite the success of combination anti-retroviral therapy, neither a vaccine nor a cure for HIV infection has been developed, demonstrating a need for novel prophylactic and therapeutic strategies. Here we show that efficiency of macrophage (M

  4. Integrated and Total HIV-1 DNA Predict Ex Vivo Viral Outgrowth.

    Directory of Open Access Journals (Sweden)

    Maja Kiselinova

    2016-03-01

    Full Text Available The persistence of a reservoir of latently infected CD4 T cells remains one of the major obstacles to cure HIV. Numerous strategies are being explored to eliminate this reservoir. To translate these efforts into clinical trials, there is a strong need for validated biomarkers that can monitor the reservoir over time in vivo. A comprehensive study was designed to evaluate and compare potential HIV-1 reservoir biomarkers. A cohort of 25 patients, treated with suppressive antiretroviral therapy was sampled at three time points, with median of 2.5 years (IQR: 2.4-2.6 between time point 1 and 2; and median of 31 days (IQR: 28-36 between time point 2 and 3. Patients were median of 6 years (IQR: 3-12 on ART, and plasma viral load (<50 copies/ml was suppressed for median of 4 years (IQR: 2-8. Total HIV-1 DNA, unspliced (us and multiply spliced HIV-1 RNA, and 2LTR circles were quantified by digital PCR in peripheral blood, at 3 time points. At the second time point, a viral outgrowth assay (VOA was performed, and integrated HIV-1 DNA and relative mRNA expression levels of HIV-1 restriction factors were quantified. No significant change was found for long- and short-term dynamics of all HIV-1 markers tested in peripheral blood. Integrated HIV-1 DNA was associated with total HIV-1 DNA (p<0.001, R² = 0.85, us HIV-1 RNA (p = 0.029, R² = 0.40, and VOA (p = 0.041, R2 = 0.44. Replication-competent virus was detected in 80% of patients by the VOA and it correlated with total HIV-1 DNA (p = 0.039, R² = 0.54. The mean quantification difference between Alu-PCR and VOA was 2.88 log10, and 2.23 log10 between total HIV-1 DNA and VOA. The levels of usHIV-1 RNA were inversely correlated with mRNA levels of several HIV-1 restriction factors (TRIM5α, SAMHD1, MX2, SLFN11, pSIP1. Our study reveals important correlations between the viral outgrowth and total and integrated HIV-1 DNA measures, suggesting that the total pool of HIV-1 DNA may predict the size of the

  5. Alemtuzumab-induced elimination of HIV-1-infected immune cells.

    Science.gov (United States)

    Ruxrungtham, Kiat; Sirivichayakul, Sunee; Buranapraditkun, Supranee; Krause, Werner

    2016-01-01

    Currently, there is no drug known that is able to eradicate either HIV or HIV-infected host cells. The effectiveness of all available treatments is based on the prevention of viral replication. We investigated whether the monoclonal, CD52 receptor-targeting antibody, alemtuzumab, which is currently approved for the treatment of multiple sclerosis, is able to eliminate HIV-infected immune cells. In blood samples from healthy donors and from HIV-1-infected subjects who were either treatment-naïve or resistant to HAART, we studied whether the CD52 expression on T cells and their subsets (CD3, CD4, CD8), B cells (CD19), dendritic cells (CD123) and monocytes (CD11c) is retained in HIV-1 infection and whether alemtuzumab is able to eradicate infected cells, using four-colour flow cytometry. We found that CD52 expression on immune cells is retained in HIV-1 infection regardless of CD4 cell count, viral load and treatment status, and is amenable to alemtuzumab-induced depletion. For the first time it could be shown in vitro that HIV-1-infected immune cells can be eliminated by using the monoclonal antibody alemtuzumab.

  6. Purinergic Receptors: Key Mediators of HIV-1 infection and inflammation

    Directory of Open Access Journals (Sweden)

    Talia H Swartz

    2015-11-01

    Full Text Available Human immunodeficiency virus (HIV-1 causes a chronic infection that afflicts more than 38 million individuals worldwide. While the infection can be suppressed with potent anti-retroviral therapies, individuals infected with HIV have elevated levels of inflammation as indicated by increased T cell activation, soluble biomarkers, and associated morbidity and mortality. A single mechanism linking HIV pathogenesis to this inflammation has yet to be identified. Purinergic receptors are known to mediate inflammation and have been shown to be required for HIV-1 infection at the level of HIV-1 membrane fusion. Here we review the literature on the role of purinergic receptors in HIV-1 infection and associated inflammation and describe a role for these receptors as potential therapeutic targets.

  7. Re-testing and misclassification of HIV-2 and HIV-1&2 dually reactive patients among the HIV-2 cohort of The West African Database to evaluate AIDS collaboration

    Science.gov (United States)

    Tchounga, Boris K; Inwoley, Andre; Coffie, Patrick A; Minta, Daouda; Messou, Eugene; Bado, Guillaume; Minga, Albert; Hawerlander, Denise; Kane, Coumba; Eholie, Serge P; Dabis, François; Ekouevi, Didier K

    2014-01-01

    Introduction West Africa is characterized by the circulation of HIV-1 and HIV-2. The laboratory diagnosis of these two infections as well as the choice of a first-line antiretroviral therapy (ART) is challenging, considering the limited access to second-line regimens. This study aimed at confirming the classification of HIV-2 and HIV-1&2 dually reactive patients followed up in the HIV-2 cohort of the West African Database to evaluate AIDS collaboration. Method A cross-sectional survey was conducted from March to December 2012 in Burkina Faso, Côte d’Ivoire and Mali among patients classified as HIV-2 or HIV-1&2 dually reactive according to the national HIV testing algorithms. A 5-ml blood sample was collected from each patient and tested in a single reference laboratory in Côte d’Ivoire (CeDReS, Abidjan) with two immuno-enzymatic tests: ImmunoCombII® (HIV-1&2 ImmunoComb BiSpot – Alere) and an in-house ELISA test, approved by the French National AIDS and hepatitis Research Agency (ANRS). Results A total of 547 patients were included; 57% of them were initially classified as HIV-2 and 43% as HIV-1&2 dually reactive. Half of the patients had CD4≥500 cells/mm3 and 68.6% were on ART. Of the 312 patients initially classified as HIV-2, 267 (85.7%) were confirmed as HIV-2 with ImmunoCombII® and in-house ELISA while 16 (5.1%) and 9 (2.9%) were reclassified as HIV-1 and HIV-1&2, respectively (Kappa=0.69; p<0.001). Among the 235 patients initially classified as HIV-1&2 dually reactive, only 54 (23.0%) were confirmed as dually reactive with ImmunoCombII® and in-house ELISA, while 103 (43.8%) and 33 (14.0%) were reclassified as HIV-1 and HIV-2 mono-infected, respectively (kappa= 0.70; p<0.001). Overall, 300 samples (54.8%) were concordantly classified as HIV-2, 63 (11.5%) as HIV-1&2 dually reactive and 119 (21.8%) as HIV-1 (kappa=0.79; p<0.001). The two tests gave discordant results for 65 samples (11.9%). Conclusions Patients with HIV-2 mono-infection are correctly

  8. Novel Latency Reversal Agents for HIV-1 Cure.

    Science.gov (United States)

    Spivak, Adam M; Planelles, Vicente

    2018-01-29

    Antiretroviral therapy (ART) has rendered HIV-1 infection a treatable illness; however, ART is not curative owing to the persistence of replication-competent, latent proviruses in long-lived resting T cells. Strategies that target these latently infected cells and allow immune recognition and clearance of this reservoir will be necessary to eradicate HIV-1 in infected individuals. This review describes current pharmacologic approaches to reactivate the latent reservoir so that infected cells can be recognized and targeted, with the ultimate goal of achieving an HIV-1 cure.

  9. Differentially-Expressed Pseudogenes in HIV-1 Infection

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    Aditi Gupta

    2015-09-01

    Full Text Available Not all pseudogenes are transcriptionally silent as previously thought. Pseudogene transcripts, although not translated, contribute to the non-coding RNA pool of the cell that regulates the expression of other genes. Pseudogene transcripts can also directly compete with the parent gene transcripts for mRNA stability and other cell factors, modulating their expression levels. Tissue-specific and cancer-specific differential expression of these “functional” pseudogenes has been reported. To ascertain potential pseudogene:gene interactions in HIV-1 infection, we analyzed transcriptomes from infected and uninfected T-cells and found that 21 pseudogenes are differentially expressed in HIV-1 infection. This is interesting because parent genes of one-third of these differentially-expressed pseudogenes are implicated in HIV-1 life cycle, and parent genes of half of these pseudogenes are involved in different viral infections. Our bioinformatics analysis identifies candidate pseudogene:gene interactions that may be of significance in HIV-1 infection. Experimental validation of these interactions would establish that retroviruses exploit this newly-discovered layer of host gene expression regulation for their own benefit.

  10. Differentially-Expressed Pseudogenes in HIV-1 Infection.

    Science.gov (United States)

    Gupta, Aditi; Brown, C Titus; Zheng, Yong-Hui; Adami, Christoph

    2015-09-29

    Not all pseudogenes are transcriptionally silent as previously thought. Pseudogene transcripts, although not translated, contribute to the non-coding RNA pool of the cell that regulates the expression of other genes. Pseudogene transcripts can also directly compete with the parent gene transcripts for mRNA stability and other cell factors, modulating their expression levels. Tissue-specific and cancer-specific differential expression of these "functional" pseudogenes has been reported. To ascertain potential pseudogene:gene interactions in HIV-1 infection, we analyzed transcriptomes from infected and uninfected T-cells and found that 21 pseudogenes are differentially expressed in HIV-1 infection. This is interesting because parent genes of one-third of these differentially-expressed pseudogenes are implicated in HIV-1 life cycle, and parent genes of half of these pseudogenes are involved in different viral infections. Our bioinformatics analysis identifies candidate pseudogene:gene interactions that may be of significance in HIV-1 infection. Experimental validation of these interactions would establish that retroviruses exploit this newly-discovered layer of host gene expression regulation for their own benefit.

  11. Acceleration of Age-Associated Methylation Patterns in HIV-1-Infected Adults

    Science.gov (United States)

    Sehl, Mary; Sinsheimer, Janet S.; Hultin, Patricia M.; Hultin, Lance E.; Quach, Austin; Martínez-Maza, Otoniel; Horvath, Steve; Vilain, Eric; Jamieson, Beth D.

    2015-01-01

    Patients with treated HIV-1-infection experience earlier occurrence of aging-associated diseases, raising speculation that HIV-1-infection, or antiretroviral treatment, may accelerate aging. We recently described an age-related co-methylation module comprised of hundreds of CpGs; however, it is unknown whether aging and HIV-1-infection exert negative health effects through similar, or disparate, mechanisms. We investigated whether HIV-1-infection would induce age-associated methylation changes. We evaluated DNA methylation levels at >450,000 CpG sites in peripheral blood mononuclear cells (PBMC) of young (20-35) and older (36-56) adults in two separate groups of participants. Each age group for each data set consisted of 12 HIV-1-infected and 12 age-matched HIV-1-uninfected samples for a total of 96 samples. The effects of age and HIV-1 infection on methylation at each CpG revealed a strong correlation of 0.49, pmodules; module 3 (ME3) was significantly correlated with age (cor=0.70) and HIV-1 status (cor=0.31). Older HIV-1+ individuals had a greater number of hypermethylated CpGs across ME3 (p=0.015). In a multivariate model, ME3 was significantly associated with age and HIV status (Data set 1: βage= 0.007088, p=2.08 x 10-9; βHIV= 0.099574, p=0.0011; Data set 2: βage= 0.008762, p=1.27x 10-5; βHIV= 0.128649, p= 0.0001). Using this model, we estimate that HIV-1 infection accelerates age-related methylation by approximately 13.7 years in data set 1 and 14.7 years in data set 2. The genes related to CpGs in ME3 are enriched for polycomb group target genes known to be involved in cell renewal and aging. The overlap between ME3 and an aging methylation module found in solid tissues is also highly significant (Fisher-exact p=5.6 x 10-6, odds ratio=1.91). These data demonstrate that HIV-1 infection is associated with methylation patterns that are similar to age-associated patterns and suggest that general aging and HIV-1 related aging work through some common cellular

  12. Discovery of natural mouse serum derived HIV-1 entry inhibitor(s).

    Science.gov (United States)

    Wei, M; Chen, Y; Xi, J; Ru, S; Ji, M; Zhang, D; Fang, Q; Tang, B

    Among rationally designed human immunodeficiency virus 1 (HIV-1) inhibitors, diverse natural factors have showed as potent anti-HIV activity in human blood. We have discovered that the boiled supernatant of healthy mouse serum could suppress HIV-1 entry, and exhibited reduced inhibitory activity after trypsin digestion. Further analysis demonstrated that only the fraction containing 10-25 K proteins could inhibit HIV-1 mediated cell-cell fusion. These results suggest that the 10-25 K protein(s) is novel natural HIV-1 entry inhibitor(s). Our findings provide important information about novel natural HIV entry inhibitors in mouse serum.

  13. THE PREVALENCE OF HUMAN IMMUNODEFIENCY VIRUS-1 (HIV-1 SUBTYPES AND TRANSMISSION METHOD AMONG HIV/AIDS INFECTION PATIENT IN TULUNGAGUNG, EAST JAVA INDONESIA

    Directory of Open Access Journals (Sweden)

    Achmad Ardianto

    2015-05-01

    Full Text Available The rapid epidemic growth of HIV is continuing in Indonesia. There are some factors which have influenced the spreading of this epidemic in Indonesia, such as the poor awareness to avoid unsafe free sex attitude and the sharing of needles and syringes among intravenous drug users (IDUs. The sexual transmission of HIV has also apparently increased in Tulungagung. Commercial sex workers play a significant role in the spread of HIV in Tulungagung. People in Tulungagung have worked at other countries as Indonesian migrants. This condition can cause the increase number of HIV-1 case and the possibility of genetic variation (subtype HIV-1 in Tulungagung. This research is aimed to analyze the subtype and to determine estimation of transmission mode on infected patient of HIV-1 and AIDS who came to Seruni clinic Dr. Iskak hospital in Tulungagung. 40 HIV?AIDSpatients were interviewed to determine the subtype and the transmission mode. The results showed that 14 of 40 plasma samples (35% were successfully to amplified and sequenced. OverallCRF01-AE wereidentified as predominant subtype among HIV/AIDS patients in Tulungagung. Based on individual information, 31 of 40 subjects (77% were heterosexual transmission.

  14. Knowledge and challenges of serodiscordant couples living among ...

    African Journals Online (AJOL)

    Depression (51.4%) was the major challenge outlined by respondents followed by social isolation (37.1%). Despite these challenges the respondents exhibited relatively good knowledge on prevention measures as 69.2% resorted to the use of condoms and 92.3% did not share sharp objects. It was also revealed that there ...

  15. Similarities and differences in the nucleic acid chaperone activity of HIV-2 and HIV-1 nucleocapsid proteins in vitro.

    Science.gov (United States)

    Pachulska-Wieczorek, Katarzyna; Stefaniak, Agnieszka K; Purzycka, Katarzyna J

    2014-07-03

    The nucleocapsid domain of Gag and mature nucleocapsid protein (NC) act as nucleic acid chaperones and facilitate folding of nucleic acids at critical steps of retroviral replication cycle. The basic N-terminus of HIV-1 NC protein was shown most important for the chaperone activity. The HIV-2 NC (NCp8) and HIV-1 NC (NCp7) proteins possess two highly conserved zinc fingers, flanked by basic residues. However, the NCp8 N-terminal domain is significantly shorter and contains less positively charged residues. This study characterizes previously unknown, nucleic acid chaperone activity of the HIV-2 NC protein. We have comparatively investigated the in vitro nucleic acid chaperone properties of the HIV-2 and HIV-1 NC proteins. Using substrates derived from the HIV-1 and HIV-2 genomes, we determined the ability of both proteins to chaperone nucleic acid aggregation, annealing and strand exchange in duplex structures. Both NC proteins displayed comparable, high annealing activity of HIV-1 TAR DNA and its complementary nucleic acid. Interesting differences between the two NC proteins were discovered when longer HIV substrates, particularly those derived from the HIV-2 genome, were used in chaperone assays. In contrast to NCp7, NCp8 weakly facilitates annealing of HIV-2 TAR RNA to its complementary TAR (-) DNA. NCp8 is also unable to efficiently stimulate tRNALys3 annealing to its respective HIV-2 PBS motif. Using truncated NCp8 peptide, we demonstrated that despite the fact that the N-terminus of NCp8 differs from that of NCp7, this domain is essential for NCp8 activity. Our data demonstrate that the HIV-2 NC protein displays reduced nucleic acid chaperone activity compared to that of HIV-1 NC. We found that NCp8 activity is limited by substrate length and stability to a greater degree than that of NCp7. This is especially interesting in light of the fact that the HIV-2 5'UTR is more structured than that of HIV-1. The reduced chaperone activity observed with NCp8 may

  16. Iron chelators ICL670 and 311 inhibit HIV-1 transcription

    International Nuclear Information System (INIS)

    Debebe, Zufan; Ammosova, Tatyana; Jerebtsova, Marina; Kurantsin-Mills, Joseph; Niu, Xiaomei; Charles, Sharroya; Richardson, Des R.; Ray, Patricio E.; Gordeuk, Victor R.; Nekhai, Sergei

    2007-01-01

    HIV-1 replication is induced by an excess of iron and iron chelation by desferrioxamine (DFO) inhibits viral replication by reducing proliferation of infected cells. Treatment of cells with DFO and 2-hydroxy-1-naphthylaldehyde isonicotinoyl hydrazone (311) inhibit expression of proteins that regulate cell-cycle progression, including cycle-dependent kinase 2 (CDK2). Our recent studies showed that CDK2 participates in HIV-1 transcription and viral replication suggesting that inhibition of CDK2 by iron chelators might also affect HIV-1 transcription. Here we evaluated the effect of a clinically approved orally effective iron chelator, 4-[3,5-bis-(hydroxyphenyl)-1,2,4-triazol-1-yl]-benzoic acid (ICL670) and 311 on HIV-1 transcription. Both ICL670 and 311 inhibited Tat-induced HIV-1 transcription in CEM-T cells, 293T and HeLa cells. Neither ICL670 nor 311 induced cytotoxicity at concentrations that inhibited HIV-1 transcription. The chelators decreased cellular activity of CDK2 and reduced HIV-1 Tat phosphorylation by CDK2. Neither ICL670A or 311 decreased CDK9 protein level but significantly reduced association of CDK9 with cyclin T1 and reduced phosphorylation of Ser-2 residues of RNA polymerase II C-terminal domain. In conclusion, our findings add to the evidence that iron chelators can inhibit HIV-1 transcription by deregulating CDK2 and CDK9. Further consideration should be given to the development of iron chelators for future anti-retroviral therapeutics

  17. Alterations in cholesterol metabolism restrict HIV-1 trans infection in nonprogressors.

    Science.gov (United States)

    Rappocciolo, Giovanna; Jais, Mariel; Piazza, Paolo; Reinhart, Todd A; Berendam, Stella J; Garcia-Exposito, Laura; Gupta, Phalguni; Rinaldo, Charles R

    2014-04-29

    ABSTRACT HIV-1-infected nonprogressors (NP) inhibit disease progression for years without antiretroviral therapy. Defining the mechanisms for this resistance to disease progression could be important in determining strategies for controlling HIV-1 infection. Here we show that two types of professional antigen-presenting cells (APC), i.e., dendritic cells (DC) and B lymphocytes, from NP lacked the ability to mediate HIV-1 trans infection of CD4(+) T cells. In contrast, APC from HIV-1-infected progressors (PR) and HIV-1-seronegative donors (SN) were highly effective in mediating HIV-1 trans infection. Direct cis infection of T cells with HIV-1 was comparably efficient among NP, PR, and SN. Lack of HIV-1 trans infection in NP was linked to lower cholesterol levels and an increase in the levels of the reverse cholesterol transporter ABCA1 (ATP-binding cassette transporter A1) in APC but not in T cells. Moreover, trans infection mediated by APC from NP could be restored by reconstitution of cholesterol and by inhibiting ABCA1 by mRNA interference. Importantly, this appears to be an inherited trait, as it was evident in APC obtained from NP prior to their primary HIV-1 infection. The present study demonstrates a new mechanism wherein enhanced lipid metabolism in APC results in remarkable control of HIV-1 trans infection that directly relates to lack of HIV-1 disease progression. IMPORTANCE HIV-1 can be captured by antigen-presenting cells (APC) such as dendritic cells and transferred to CD4 helper T cells, which results in greatly enhanced viral replication by a mechanism termed trans infection. A small percentage of HIV-1-infected persons are able to control disease progression for many years without antiretroviral therapy. In our study, we linked this lack of disease progression to a profound inability of APC from these individuals to trans infect T cells. This effect was due to altered lipid metabolism in their APC, which appears to be an inherited trait. These

  18. Rapid Antiretroviral Therapy Initiation for Women in an HIV-1 Prevention Clinical Trial Experiencing Primary HIV-1 Infection during Pregnancy or Breastfeeding.

    Science.gov (United States)

    Morrison, Susan; John-Stewart, Grace; Egessa, John J; Mubezi, Sezi; Kusemererwa, Sylvia; Bii, Dennis K; Bulya, Nulu; Mugume, Francis; Campbell, James D; Wangisi, Jonathan; Bukusi, Elizabeth A; Celum, Connie; Baeten, Jared M

    2015-01-01

    During an HIV-1 prevention clinical trial in East Africa, we observed 16 cases of primary HIV-1 infection in women coincident with pregnancy or breastfeeding. Nine of eleven pregnant women initiated rapid combination antiretroviral therapy (ART), despite having CD4 counts exceeding national criteria for ART initiation; breastfeeding women initiated ART or replacement feeding. Rapid ART initiation during primary HIV-1 infection during pregnancy and breastfeeding is feasible in this setting.

  19. Rapid Antiretroviral Therapy Initiation for Women in an HIV-1 Prevention Clinical Trial Experiencing Primary HIV-1 Infection during Pregnancy or Breastfeeding.

    Directory of Open Access Journals (Sweden)

    Susan Morrison

    Full Text Available During an HIV-1 prevention clinical trial in East Africa, we observed 16 cases of primary HIV-1 infection in women coincident with pregnancy or breastfeeding. Nine of eleven pregnant women initiated rapid combination antiretroviral therapy (ART, despite having CD4 counts exceeding national criteria for ART initiation; breastfeeding women initiated ART or replacement feeding. Rapid ART initiation during primary HIV-1 infection during pregnancy and breastfeeding is feasible in this setting.

  20. Interleukin-10 (IL-10) pathway: genetic variants and outcomes of HIV-1 infection in African American adolescents.

    Science.gov (United States)

    Shrestha, Sadeep; Wiener, Howard W; Aissani, Brahim; Song, Wei; Shendre, Aditi; Wilson, Craig M; Kaslow, Richard A; Tang, Jianming

    2010-10-14

    Immunological and clinical outcomes can vary considerably at the individual and population levels during both treated and untreated HIV-1 infection. Cytokines encoded by the interleukin-10 gene (IL10) family have broad immunomodulatory function in viral persistence, and several SNPs in the IL10 promoter sequence have been reported to influence pathogenesis or acquisition of HIV-1 infection. We examined 104 informative SNPs in IL10, IL19, IL20, IL24, IL10RA and IL10RB among 250 HIV-1 seropositive and 106 high-risk seronegative African American adolescents in the REACH cohort. In subsequent evaluation of five different immunological and virological outcomes related to HIV-1 infection, 25 SNPs were associated with a single outcome and three were associated with two different outcomes. One SNP, rs2243191 in the IL19 open reading frame (Ser to Phe substitution) was associated with CD4(+) T-cell increase during treatment. Another SNP rs2244305 in IL10RB (in strong linkage disequilibrium with rs443498) was associated with an initial decrease in CD4(+) T-cell by 23 ± 9% and 29 ± 9% every 3 months (for AA and AG genotypes, respectively, compared with GG) during ART-free period. These associations were reversed during treatment, as CD4(+) T-cell increased by 31 ± 0.9% and 17 ± 8% every 3 months for AA and AG genotype, respectively. In African Americans, variants in IL10 and related genes might influence multiple outcomes of HIV-1 infection, especially immunological response to HAART. Fine mapping coupled with analysis of gene expression and function should help reveal the immunological importance of the IL10 gene family to HIV-1/AIDS.

  1. Performance comparison of the 4th generation Bio-Rad Laboratories GS HIV Combo Ag/Ab EIA on the EVOLIS™ automated system versus Abbott ARCHITECT HIV Ag/Ab Combo, Ortho Anti-HIV 1+2 EIA on Vitros ECi and Siemens HIV-1/O/2 enhanced on Advia Centaur.

    Science.gov (United States)

    Mitchell, Elizabeth O; Stewart, Greg; Bajzik, Olivier; Ferret, Mathieu; Bentsen, Christopher; Shriver, M Kathleen

    2013-12-01

    A multisite study was conducted to evaluate the performance of the Bio-Rad 4th generation GS HIV Combo Ag/Ab EIA versus Abbott 4th generation ARCHITECT HIV Ag/Ab Combo. The performance of two 3rd generation EIAs, Ortho Diagnostics Anti-HIV 1+2 EIA and Siemens HIV 1/O/2 was also evaluated. Study objective was comparison of analytical HIV-1 p24 antigen detection, sensitivity in HIV-1 seroconversion panels, specificity in blood donors and two HIV false reactive panels. Analytical sensitivity was evaluated with International HIV-1 p24 antigen standards, the AFFSAPS (pg/mL) and WHO 90/636 (IU/mL) standards; sensitivity in acute infection was compared on 55 seroconversion samples, and specificity was evaluated on 1000 negative blood donors and two false reactive panels. GS HIV Combo Ag/Ab demonstrated better analytical HIV antigen sensitivity compared to ARCHITECT HIV Ag/Ab Combo: 0.41 IU/mL versus 1.2 IU/mL (WHO) and 12.7 pg/mL versus 20.1 pg/mL (AFSSAPS); GS HIV Combo Ag/Ab EIA also demonstrated slightly better specificity compared to ARCHITECT HIV Ag/Ab Combo (100% versus 99.7%). The 4th generation HIV Combo tests detected seroconversion 7-11 days earlier than the 3rd generation HIV antibody only EIAs. Both 4th generation immunoassays demonstrated excellent performance in sensitivity, with the reduction of the serological window period (7-11 days earlier detection than the 3rd generation HIV tests). However, GS HIV Combo Ag/Ab demonstrated improved HIV antigen analytical sensitivity and slightly better specificity when compared to ARCHITECT HIV Ag/Ab Combo assay, with higher positive predictive values (PPV) for low prevalence populations. Copyright © 2013 Elsevier B.V. All rights reserved.

  2. Direct effects of HIV-1 Tat on excitability and survival of primary dorsal root ganglion neurons: possible contribution to HIV-1-associated pain.

    Directory of Open Access Journals (Sweden)

    Xianxun Chi

    Full Text Available The vast majority of people living with human immunodeficiency virus type 1 (HIV-1 have pain syndrome, which has a significant impact on their quality of life. The underlying causes of HIV-1-associated pain are not likely attributable to direct viral infection of the nervous system due to the lack of evidence of neuronal infection by HIV-1. However, HIV-1 proteins are possibly involved as they have been implicated in neuronal damage and death. The current study assesses the direct effects of HIV-1 Tat, one of potent neurotoxic viral proteins released from HIV-1-infected cells, on the excitability and survival of rat primary dorsal root ganglion (DRG neurons. We demonstrated that HIV-1 Tat triggered rapid and sustained enhancement of the excitability of small-diameter rat primary DRG neurons, which was accompanied by marked reductions in the rheobase and resting membrane potential (RMP, and an increase in the resistance at threshold (R(Th. Such Tat-induced DRG hyperexcitability may be a consequence of the inhibition of cyclin-dependent kinase 5 (Cdk5 activity. Tat rapidly inhibited Cdk5 kinase activity and mRNA production, and roscovitine, a well-known Cdk5 inhibitor, induced a very similar pattern of DRG hyperexcitability. Indeed, pre-application of Tat prevented roscovitine from having additional effects on the RMP and action potentials (APs of DRGs. However, Tat-mediated actions on the rheobase and R(Th were accelerated by roscovitine. These results suggest that Tat-mediated changes in DRG excitability are partly facilitated by Cdk5 inhibition. In addition, Cdk5 is most abundant in DRG neurons and participates in the regulation of pain signaling. We also demonstrated that HIV-1 Tat markedly induced apoptosis of primary DRG neurons after exposure for longer than 48 h. Together, this work indicates that HIV-1 proteins are capable of producing pain signaling through direct actions on excitability and survival of sensory neurons.

  3. Acceleration of age-associated methylation patterns in HIV-1-infected adults.

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    Tammy M Rickabaugh

    Full Text Available Patients with treated HIV-1-infection experience earlier occurrence of aging-associated diseases, raising speculation that HIV-1-infection, or antiretroviral treatment, may accelerate aging. We recently described an age-related co-methylation module comprised of hundreds of CpGs; however, it is unknown whether aging and HIV-1-infection exert negative health effects through similar, or disparate, mechanisms. We investigated whether HIV-1-infection would induce age-associated methylation changes. We evaluated DNA methylation levels at >450,000 CpG sites in peripheral blood mononuclear cells (PBMC of young (20-35 and older (36-56 adults in two separate groups of participants. Each age group for each data set consisted of 12 HIV-1-infected and 12 age-matched HIV-1-uninfected samples for a total of 96 samples. The effects of age and HIV-1 infection on methylation at each CpG revealed a strong correlation of 0.49, p<1 x 10(-200 and 0.47, p<1 x 10(-200. Weighted gene correlation network analysis (WGCNA identified 17 co-methylation modules; module 3 (ME3 was significantly correlated with age (cor=0.70 and HIV-1 status (cor=0.31. Older HIV-1+ individuals had a greater number of hypermethylated CpGs across ME3 (p=0.015. In a multivariate model, ME3 was significantly associated with age and HIV status (Data set 1: βage=0.007088, p=2.08 x 10(-9; βHIV=0.099574, p=0.0011; Data set 2: βage=0.008762, p=1.27 x 10(-5; βHIV=0.128649, p=0.0001. Using this model, we estimate that HIV-1 infection accelerates age-related methylation by approximately 13.7 years in data set 1 and 14.7 years in data set 2. The genes related to CpGs in ME3 are enriched for polycomb group target genes known to be involved in cell renewal and aging. The overlap between ME3 and an aging methylation module found in solid tissues is also highly significant (Fisher-exact p=5.6 x 10(-6, odds ratio=1.91. These data demonstrate that HIV-1 infection is associated with methylation patterns that

  4. Molecular and epidemiological characterization of HIV-1 subtypes among Libyan patients.

    Science.gov (United States)

    Daw, Mohamed A; El-Bouzedi, Abdallah; Ahmed, Mohamed O; Dau, Aghnyia A

    2017-04-28

    The epidemiological and clinical aspects of human immunodeficiency virus subtypes are of great interest worldwide. These subtypes are rarely studied in North African countries. Libya is a large country with the longest coast on the Mediterranean Sea, facing the Southern European countries. Studies on the characterization of HIV-1 subtypes are limited in Libya. This study aimed to determine the magnitude of the HIV problem among the Libyan population and to better understand the genetic diversity and the epidemiologic dynamics of HIV 1, as well as to correlate that with the risk factors involved. A total of 159 HIV-1 strains were collected from 814 HIV positive patients from the four Libyan regions during a 16-year period (1995-2010). To determine the HIV-1 subtypes, genetic analysis and molecular sequencing were carried out using provirus polygene. Epidemiologic and demographic information was obtained from each participant and correlated with HIV-1 subtypes using logistic regression. The overall prevalence of HIV among Libyans ranged from 5 to 10 per 100,000 during the study period. It was higher among intravenous drug users (IVDUs) (53.9%), blood recipients (25.9%) and heterosexuals (17.6%) than by vertical transmission (2.6%). Prevalence was higher among males aged 20-40 years (M:F 1:6, P > 0.001). Among the 159 strains of HIV-1 available for typing, 117 strains (73.6%) were subtype B, 29 (18.2%) were CRF02_AG, and 13 (8.2%) were subtype A. HIV-1 subtype B was the most prevalent all over the country, and it was more prevalent in the Northern region, particularly among IVDUs (P HIV-1 infection is emerging in Libya with a shifting prevalence of subtypes associated with the changing epidemiology of HIV-1 among risk groups. A genetic analysis of HIV-1 strains demonstrated low subtype heterogeneity with the evolution of subtype B, and CRF_20 AG, as well as HIV-1 subtype A. Our study highlights the importance of expanded surveillance programs to control HIV

  5. Ebselen, a Small-Molecule Capsid Inhibitor of HIV-1 Replication.

    Science.gov (United States)

    Thenin-Houssier, Suzie; de Vera, Ian Mitchelle S; Pedro-Rosa, Laura; Brady, Angela; Richard, Audrey; Konnick, Briana; Opp, Silvana; Buffone, Cindy; Fuhrmann, Jakob; Kota, Smitha; Billack, Blase; Pietka-Ottlik, Magdalena; Tellinghuisen, Timothy; Choe, Hyeryun; Spicer, Timothy; Scampavia, Louis; Diaz-Griffero, Felipe; Kojetin, Douglas J; Valente, Susana T

    2016-04-01

    The human immunodeficiency virus type 1 (HIV-1) capsid plays crucial roles in HIV-1 replication and thus represents an excellent drug target. We developed a high-throughput screening method based on a time-resolved fluorescence resonance energy transfer (HTS-TR-FRET) assay, using the C-terminal domain (CTD) of HIV-1 capsid to identify inhibitors of capsid dimerization. This assay was used to screen a library of pharmacologically active compounds, composed of 1,280in vivo-active drugs, and identified ebselen [2-phenyl-1,2-benzisoselenazol-3(2H)-one], an organoselenium compound, as an inhibitor of HIV-1 capsid CTD dimerization. Nuclear magnetic resonance (NMR) spectroscopic analysis confirmed the direct interaction of ebselen with the HIV-1 capsid CTD and dimer dissociation when ebselen is in 2-fold molar excess. Electrospray ionization mass spectrometry revealed that ebselen covalently binds the HIV-1 capsid CTD, likely via a selenylsulfide linkage with Cys198 and Cys218. This compound presents anti-HIV activity in single and multiple rounds of infection in permissive cell lines as well as in primary peripheral blood mononuclear cells. Ebselen inhibits early viral postentry events of the HIV-1 life cycle by impairing the incoming capsid uncoating process. This compound also blocks infection of other retroviruses, such as Moloney murine leukemia virus and simian immunodeficiency virus, but displays no inhibitory activity against hepatitis C and influenza viruses. This study reports the use of TR-FRET screening to successfully identify a novel capsid inhibitor, ebselen, validating HIV-1 capsid as a promising target for drug development. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  6. Identification of conserved subdominant HIV Type 1 CD8(+) T Cell epitopes restricted within common HLA Supertypes for therapeutic HIV Type 1 vaccines

    DEFF Research Database (Denmark)

    Karlsson, Ingrid; Kløverpris, Henrik; Jensen, Kristoffer Jarlov

    2012-01-01

    The high HIV-1 prevalence, up to 4.6% in Guinea-Bissau, West Africa, makes it a relevant location for testing of therapeutic vaccines. With the aim of performing a clinical study in Guinea-Bissau, after first testing the vaccine for safety in Denmark, Europe, we here describe the design...... of a universal epitope peptide-based T cell vaccine with relevance for any geographic locations. The two major obstacles when designing such a vaccine are the high diversities of the HIV-1 genome and of the human major histocompatibility complex (MHC) class I. We selected 15 CD8-restricted epitopes predicted......-specific, HLA-restricted T cell specificities using peptide-MHC class I tetramer labeling of CD8(+) T cells from HIV-1-infected individuals. The selected vaccine epitopes are infrequently targeted in HIV-1-infected individuals from both locations. Moreover, we HLA-typed HIV-1-infected individuals...

  7. Development of TIMP1 magnetic nanoformulation for regulation of synaptic plasticity in HIV-1 infection

    Directory of Open Access Journals (Sweden)

    Atluri VSR

    2016-08-01

    Full Text Available Venkata Subba Rao Atluri* Rahul Dev Jayant* Sudheesh Pilakka-Kanthikeel, Gabriella Garcia, Thangavel Samikkannu, Adriana Yndart, Ajeet Kaushik, Madhavan Nair Center for Personalized Nanomedicine, Department of Immunology, Herbert Wertheim College of Medicine, Florida International University, Miami, FL, USA *These authors contributed equally to this work Abstract: Although the introduction of antiretroviral therapy has reduced the prevalence of severe forms of neurocognitive disorders, human immunodeficiency virus (HIV-1-associated neurocognitive disorders were observed in 50% of HIV-infected patients globally. The blood–brain barrier is known to be impermeable to most of antiretroviral drugs. Successful delivery of antiretroviral drugs into the brain may induce an inflammatory response, which may further induce neurotoxicity. Therefore, alternate options to antiretroviral drugs for decreasing the HIV infection and neurotoxicity may help in reducing neurocognitive impairments observed in HIV-infected patients. In this study, we explored the role of magnetic nanoparticle (MNP-bound tissue inhibitor of metalloproteinase-1 (TIMP1 protein in reducing HIV infection levels, oxidative stress, and recovering spine density in HIV-infected SK-N-MC neuroblastoma cells. We did not observe any neuronal cytotoxicity with either the free TIMP1 or MNP-bound TIMP1 used in our study. We observed significantly reduced HIV infection in both solution phase and in MNP-bound TIMP1-exposed neuronal cells. Furthermore, we also observed significantly reduced reactive oxygen species production in both the test groups compared to the neuronal cells infected with HIV alone. To observe the effect of both soluble-phase TIMP1 and MNP-bound TIMP1 on spine density in HIV-infected neuronal cells, confocal microscopy was used. We observed significant recovery of spine density in both the test groups when compared to the cells infected with HIV alone, indicting the

  8. Continued Follow-Up of Phambili Phase 2b Randomized HIV-1 Vaccine Trial Participants Supports Increased HIV-1 Acquisition among Vaccinated Men.

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    Zoe Moodie

    Full Text Available The Phase 2b double-blinded, randomized Phambili/HVTN 503 trial evaluated safety and efficacy of the MRK Ad5 gag/pol/nef subtype B HIV-1 preventive vaccine vs placebo in sexually active HIV-1 seronegative participants in South Africa. Enrollment and vaccinations stopped and participants were unblinded but continued follow-up when the Step study evaluating the same vaccine in the Americas, Caribbean, and Australia was unblinded for non-efficacy. Final Phambili analyses found more HIV-1 infections amongst vaccine than placebo recipients, impelling the HVTN 503-S recall study.HVTN 503-S sought to enroll all 695 HIV-1 uninfected Phambili participants, provide HIV testing, risk reduction counseling, physical examination, risk behavior assessment and treatment assignment recall. After adding HVTN 503-S data, HIV-1 infection hazard ratios (HR vaccine vs. placebo were estimated by Cox models.Of the 695 eligible, 465 (67% enrolled with 230 from the vaccine group and 235 from the placebo group. 38% of the 184 Phambili dropouts were enrolled. Enrollment did not differ by treatment group, gender, or baseline HSV-2. With the additional 1286 person years of 503-S follow-up, the estimated HR over Phambili and HVTN 503-S follow-up was 1.52 (95% CI 1.08-2.15, p = 0.02, 82 vaccine/54 placebo infections. The HR was significant for men (HR = 2.75, 95% CI 1.49, 5.06, p = 0.001 but not for women (HR = 1.12, 95% CI 0.73, 1.72, p = 0.62.The additional follow-up from HVTN 503-S supported the Phambili finding of increased HIV-1 acquisition among vaccinated men and strengthened the evidence of lack of vaccine effect among women.clinicaltrials.gov NCT00413725 SA National Health Research Database DOH-27-0207-1539.

  9. Syphilis and HIV-1 co-infection: influence on CD4 T cell count, HIV-1 viral load and treatment response

    DEFF Research Database (Denmark)

    Kofoed, Kristian; Gerstoft, Jan; Mathiesen, Lars Reinhardt

    2006-01-01

    OBJECTIVES: To assess the effect of human immunodeficiency virus (HIV)-1 and syphilis coinfection on HIV-ribonucleic acid (RNA) viral load, CD4 cell count, and the response in rapid plasmin reagin (RPR) to treatment of the syphilis infection. STUDY DESIGN: Cases of syphilis diagnosed during 1 year...... in HIV-infected patients in Copenhagen were included. HIV-RNA, CD4 cell counts, and RPR-serology were measured before, during, and after syphilis. RESULTS: Forty-one patients were included. CD4 cell count decreased significantly during infection in patients with primary and secondary stages of syphilis...... (mean 106 cells/mm, P = 0.03). Treatment of syphilis was associated with an increase in the CD4 cell count and a decrease in HIV-RNA in the overall group (mean 66 cells/mm and -0.261 RNA log10 copies/ml, P = 0.02 and 0.04). The serological response rates for 15 patients treated with penicillin and 25...

  10. A prospective study of the effect of pregnancy on CD4 counts and plasma HIV-1 RNA concentrations of antiretroviral-naive HIV-1-infected women.

    Science.gov (United States)

    Heffron, Renee; Donnell, Deborah; Kiarie, James; Rees, Helen; Ngure, Kenneth; Mugo, Nelly; Were, Edwin; Celum, Connie; Baeten, Jared M

    2014-02-01

    In HIV-1-infected women, CD4 count declines occur during pregnancy, which has been attributed to hemodilution. However, for women who have not initiated antiretroviral therapy, it is unclear if CD4 declines are sustained beyond pregnancy and accompanied by increased viral levels, which could indicate an effect of pregnancy on accelerating HIV-1 disease progression. In a prospective study among 2269 HIV-1-infected antiretroviral therapy-naive women from 7 African countries, we examined the effect of pregnancy on HIV-1 disease progression. We used linear mixed models to compare CD4 counts and plasma HIV-1 RNA concentrations between pregnant, postpartum, and nonpregnant periods. Women contributed 3270 person-years of follow-up, during which time 476 women became pregnant. In adjusted analysis, CD4 counts were an average of 56 (95% confidence interval: 39 to 73) cells/mm lower during pregnant compared with nonpregnant periods and 70 (95% confidence interval: 53 to 88) cells/mm lower during pregnant compared with postpartum periods; these results were consistent when restricted to the subgroup of women who became pregnant. Plasma HIV-1 RNA concentrations were not different between pregnant and nonpregnant periods (P = 0.9) or pregnant and postpartum periods (P = 0.3). Neither CD4 counts nor plasma HIV-1 RNA levels were significantly different in postpartum compared with nonpregnant periods. CD4 count declines among HIV-1-infected women during pregnancy are temporary and not sustained in postpartum periods. Pregnancy does not have a short-term impact on plasma HIV-1 RNA concentrations.

  11. Creation of chimeric human/rabbit APOBEC1 with HIV-1 restriction and DNA mutation activities

    Science.gov (United States)

    Ikeda, Terumasa; Ong, Eugene Boon Beng; Watanabe, Nobumoto; Sakaguchi, Nobuo; Maeda, Kazuhiko; Koito, Atsushi

    2016-01-01

    APOBEC1 (A1) proteins from lagomorphs and rodents have deaminase-dependent restriction activity against HIV-1, whereas human A1 exerts a negligible effect. To investigate these differences in the restriction of HIV-1 by A1 proteins, a series of chimeric proteins combining rabbit and human A1s was constructed. Homology models of the A1s indicated that their activities derive from functional domains that likely act in tandem through a dimeric interface. The C-terminal region containing the leucine-rich motif and the dimerization domains of rabbit A1 is important for its anti-HIV-1 activity. The A1 chimeras with strong anti-HIV-1 activity were incorporated into virions more efficiently than those without anti-HIV-1 activity, and exhibited potent DNA-mutator activity. Therefore, the C-terminal region of rabbit A1 is involved in both its packaging into the HIV-1 virion and its deamination activity against both viral cDNA and genomic RNA. This study identifies the novel molecular mechanism underlying the target specificity of A1.

  12. A single gp120 residue can affect HIV-1 tropism in macaques.

    Directory of Open Access Journals (Sweden)

    Gregory Q Del Prete

    2017-09-01

    Full Text Available Species-dependent variation in proteins that aid or limit virus replication determines the ability of lentiviruses to jump between host species. Identifying and overcoming these differences facilitates the development of animal models for HIV-1, including models based on chimeric SIVs that express HIV-1 envelope (Env glycoproteins, (SHIVs and simian-tropic HIV-1 (stHIV strains. Here, we demonstrate that the inherently poor ability of most HIV-1 Env proteins to use macaque CD4 as a receptor is improved during adaptation by virus passage in macaques. We identify a single amino acid, A281, in HIV-1 Env that consistently changes during adaptation in macaques and affects the ability of HIV-1 Env to use macaque CD4. Importantly, mutations at A281 do not markedly affect HIV-1 Env neutralization properties. Our findings should facilitate the design of HIV-1 Env proteins for use in non-human primate models and thus expedite the development of clinically relevant reagents for testing interventions against HIV-1.

  13. Extracellular histones identified in crocodile blood inhibit in-vitro HIV-1 infection.

    Science.gov (United States)

    Kozlowski, Hannah N; Lai, Eric T L; Havugimana, Pierre C; White, Carl; Emili, Andrew; Sakac, Darinka; Binnington, Beth; Neschadim, Anton; McCarthy, Stephen D S; Branch, Donald R

    2016-08-24

    It has been reported that crocodile blood contains potent antibacterial and antiviral properties. However, its effects on HIV-1 infection remain unknown. We obtained blood from saltwater crocodiles to examine whether serum or plasma could inhibit HIV-1 infection. We purified plasma fractions then used liquid chromatography-mass spectrometry to identify the inhibitory protein factor(s). We then analyzed the ability of recombinant proteins to recapitulate HIV-1 inhibition and determine their mechanism of action. Crocodylus porosus plasma was tested for inhibition of Jurkat T-cell HIV-1 infection. Inhibitor(s) were purified by reverse-phase chromatography then identified by protein liquid chromatography-mass spectrometry. Anti-HIV-1 activity of purified plasma or recombinant proteins were measured by p24 enzyme-linked immunosorbent assay and luciferase readouts, and mechanism of action was determined by measuring HIV-1 RNA, cDNA and transcription (using 1G5 cells). Crocodile plasma contains potent inhibitors of HIV-1IIIB infection, which were identified as histones. Recombinant human histones H1 and H2A significantly reduced HIV-1JR-FL infection (IC50 of 0.79 and 0.45 μmol/l, respectively), whereas H4 enhanced JR-FL luciferase activity. The inhibitory effects of crocodile plasma, recombinant H1 or recombinant H2A on HIV-1 infection were during or post-viral transcription. Circulating histones in crocodile blood, possibly released by neutrophil extracellular traps, are significant inhibitors of HIV-1 infection in-vitro. Extracellular recombinant histones have different effects on HIV-1 transcription and protein expression and are downregulated in HIV-1 patients. Circulating histones may be a novel resistance factor during HIV-1 infection, and peptide versions should be explored as future HIV-1 therapeutics that modulate viral transcription.

  14. HIV-1 transgenic rats develop T cell abnormalities

    International Nuclear Information System (INIS)

    Reid, William; Abdelwahab, Sayed; Sadowska, Mariola; Huso, David; Neal, Ashley; Ahearn, Aaron; Bryant, Joseph; Gallo, Robert C.; Lewis, George K.; Reitz, Marvin

    2004-01-01

    HIV-1 infection leads to impaired antigen-specific T cell proliferation, increased susceptibility of T cells to apoptosis, progressive impairment of T-helper 1 (Th1) responses, and altered maturation of HIV-1-specific memory cells. We have identified similar impairments in HIV-1 transgenic (Tg) rats. Tg rats developed an absolute reduction in CD4 + and CD8 + T cells able to produce IFN-γ following activation and an increased susceptibility of T cells to activation-induced apoptosis. CD4 + and CD8 + effector/memory (CD45RC - CD62L - ) pools were significantly smaller in Tg rats compared to non-Tg controls, although the converse was true for the naieve (CD45RC + CD62L + ) T cell pool. Our interpretation is that the HIV transgene causes defects in the development of T cell effector function and generation of specific effector/memory T cell subsets, and that activation-induced apoptosis may be an essential factor in this process

  15. Creatine protects against mitochondrial dysfunction associated with HIV-1 Tat-induced neuronal injury

    Science.gov (United States)

    Stevens, Patrick R.; Gawryluk, Jeremy W.; Hui, Liang; Chen, Xuesong; Geiger, Jonathan D.

    2015-01-01

    HIV-1 infected individuals are living longer but experiencing a prevalence rate of over 50% for HIV-1 associated neurocognitive disorders (HAND) for which no effective treatment is available. Viral and cellular factors secreted by HIV-1 infected cells leads to neuronal injury and HIV-1 Tat continues to be implicated in the pathogenesis of HAND. Here we tested the hypothesis that creatine protected against HIV-1 Tat-induced neuronal injury by preventing mitochondrial bioenergetic crisis and/or redox catastrophe. Creatine blocked HIV-1 Tat1-72-induced increases in neuron cell death and synaptic area loss. Creatine protected against HIV-1 Tat-induced decreases in ATP. Creatine and creatine plus HIV-1 Tat increased cellular levels of creatine, and creatine plus HIV-1 Tat further decreased ratios of phosphocreatine to creatine observed with creatine or HIV-1 Tat treatments alone. Additionally, creatine protected against HIV-1 Tat-induced mitochondrial hypopolarization and HIV-1 Tat-induced mitochondrial permeability transition pore opening. Thus, creatine may be a useful adjunctive therapy against HAND. PMID:25613139

  16. Ethical Dilemma and Management of Infertility in HIV Seropositive Discordant Couples: A Case Study in Nigeria.

    Science.gov (United States)

    Umeora, Ouj; Chukwuneke, Fn

    2013-01-01

    The traditional African society places an invaluable premium on procreation and, in some communities, a woman's place in her matrimony is only confirmed on positive reproductive outcome. Infertility is rife in Nigeria, and HIV/acquired immunodeficiency syndrome (AIDS) infection is a global pandemic, which has led to a drop in life expectancy across the world. In Nigeria, a number of cultural norms relating to gender roles and power dynamics constitute a serious barrier to issues of sexuality and infertility. Couples are concerned about their infertility diagnostic test being disclosed to each other, especially before marriage. This concern is understandable, especially in an environment that lacks the modern concepts and attitude toward sexual matters. This is complicated by the advent of HIV/AIDS infection and the societal mind-set that look at seropostive individuals as transgressors. At present, sexual and reproductive health rights are currently not in place because ethical issues are not given prominence by many physicians in Nigeria. A case of an infertile and seropostive discordant couple, which raised a lot of medical and ethical concerns, is presented here to awaken the consciousness of Nigerian physicians and stimulate discussions on the ethical matters such as this in clinical practice.

  17. HIV-1 nef suppression by virally encoded microRNA

    Directory of Open Access Journals (Sweden)

    Brisibe Ebiamadon

    2004-12-01

    Full Text Available Abstract Background MicroRNAs (miRNAs are 21~25-nucleotides (nt long and interact with mRNAs to trigger either translational repression or RNA cleavage through RNA interference (RNAi, depending on the degree of complementarity with the target mRNAs. Our recent study has shown that HIV-1 nef dsRNA from AIDS patients who are long-term non-progressors (LTNPs inhibited the transcription of HIV-1. Results Here, we show the possibility that nef-derived miRNAs are produced in HIV-1 persistently infected cells. Furthermore, nef short hairpin RNA (shRNA that corresponded to a predicted nef miRNA (~25 nt, miR-N367 can block HIV-1 Nef expression in vitro and the suppression by shRNA/miR-N367 would be related with low viremia in an LTNP (15-2-2. In the 15-2-2 model mice, the weight loss, which may be rendered by nef was also inhibited by shRNA/miR-N367 corresponding to suppression of nef expression in vivo. Conclusions These data suggest that nef/U3 miRNAs produced in HIV-1-infected cells may suppress both Nef function and HIV-1 virulence through the RNAi pathway.

  18. Diabetes mellitus and impaired fasting glucose in ART-naïve patients with HIV-1, HIV-2 and HIV-1/2 dual infection in Guinea-Bissau

    DEFF Research Database (Denmark)

    Steiniche, Ditte; Jespersen, Sanne; Erikstrup, Christian

    2016-01-01

    BACKGROUND: The prevalence of diabetes mellitus (DM) is expected to increase in sub-Saharan Africa. Patients with HIV are at particular risk. We investigated the DM burden among antiretroviral therapy (ART)-naïve patients with HIV in Guinea-Bissau. METHODS: Patients were consecutively included. D...... age and a family history of DM apply also for ART-naïve patients with HIV.......BACKGROUND: The prevalence of diabetes mellitus (DM) is expected to increase in sub-Saharan Africa. Patients with HIV are at particular risk. We investigated the DM burden among antiretroviral therapy (ART)-naïve patients with HIV in Guinea-Bissau. METHODS: Patients were consecutively included....... Demographic and lifestyle data were collected and one fasting blood glucose (FBG) measurement was used to diagnose DM (FBG≥7.0 mmol/L) and impaired fasting glucose (IFG) (FBG≥6.1 and ART-naïve patients with HIV had been included in the study of whom 893...

  19. Ectopic expression of anti-HIV-1 shRNAs protects CD8+ T cells modified with CD4ζ CAR from HIV-1 infection and alleviates impairment of cell proliferation

    International Nuclear Information System (INIS)

    Kamata, Masakazu; Kim, Patrick Y.; Ng, Hwee L.; Ringpis, Gene-Errol E.; Kranz, Emiko; Chan, Joshua; O'Connor, Sean; Yang, Otto O.; Chen, Irvin S.Y.

    2015-01-01

    Chimeric antigen receptors (CARs) are artificially engineered receptors that confer a desired specificity to immune effector T cells. As an HIV-1-specific CAR, CD4ζ CAR has been extensively tested in vitro as well as in clinical trials. T cells modified with this CAR mediated highly potent anti-HIV-1 activities in vitro and were well-tolerated in vivo, but exerted limited effects on viral load and reservoir size due to poor survival and/or functionality of the transduced cells in patients. We hypothesize that ectopic expression of CD4ζ on CD8 + T cells renders them susceptible to HIV-1 infection, resulting in poor survival of those cells. To test this possibility, highly purified CD8 + T cells were genetically modified with a CD4ζ-encoding lentiviral vector and infected with HIV-1. CD8 + T cells were vulnerable to HIV-1 infection upon expression of CD4ζ as evidenced by elevated levels of p24 Gag in cells and culture supernatants. Concurrently, the number of CD4ζ-modified CD8 + T cells was reduced relative to control cells upon HIV-1 infection. To protect these cells from HIV-1 infection, we co-expressed two anti-HIV-1 shRNAs previously developed by our group together with CD4ζ. This combination vector was able to suppress HIV-1 infection without impairing HIV-1-dependent effector activities of CD4ζ. In addition, the number of CD4ζ-modified CD8 + T cells maintained similar levels to that of the control even under HIV-1 infection. These results suggest that protecting CD4ζ-modified CD8 + T cells from HIV-1 infection is required for prolonged HIV-1-specific immune surveillance. - Highlights: • Ectopic expression of CD4ζ CAR in CD8 + T cells renders them susceptible to HIV-1 infection. • Co-expression of two anti-HIV-1 shRNAs protects CD4ζ CAR-modified CD8 + T cells from HIV-1 infection. • Protecting CD4ζ CAR-modified CD8 + T cells from HIV-1 infection suppresses its cytopathic effect

  20. The Latent Reservoir for HIV-1: How Immunologic Memory and Clonal Expansion Contribute to HIV-1 Persistence

    Science.gov (United States)

    Murray, Alexandra J.; Kwon, Kyungyoon J.; Farber, Donna L.; Siliciano, Robert F.

    2016-01-01

    Combination antiretroviral therapy (ART) for HIV-1 infection reduces plasma virus levels to below the limit of detection of clinical assays. However, even with prolonged suppression of viral replication with ART, viremia rebounds rapidly after treatment interruption. Thus ART is not curative. The principal barrier to cure is a remarkably stable reservoir of latent HIV-1 in resting memory CD4+ T cells. Here we consider explanations for the remarkable stability of the latent reservoir. Stability does not appear to reflect replenishment from new infection events but rather normal physiologic processes that provide for immunologic memory. Of particular importance are proliferative processes that drive clonal expansion of infected cells. Recent evidence suggests that in some infected cells, proliferation is a consequence of proviral integration into host genes associated with cell growth. Efforts to cure HIV-1 infection by targeting the latent reservoir may need to consider the potential of latently infected cells to proliferate. PMID:27382129

  1. HIV-1 DNA predicts disease progression and post-treatment virological control

    Science.gov (United States)

    Williams, James P; Hurst, Jacob; Stöhr, Wolfgang; Robinson, Nicola; Brown, Helen; Fisher, Martin; Kinloch, Sabine; Cooper, David; Schechter, Mauro; Tambussi, Giuseppe; Fidler, Sarah; Carrington, Mary; Babiker, Abdel; Weber, Jonathan

    2014-01-01

    In HIV-1 infection, a population of latently infected cells facilitates viral persistence despite antiretroviral therapy (ART). With the aim of identifying individuals in whom ART might induce a period of viraemic control on stopping therapy, we hypothesised that quantification of the pool of latently infected cells in primary HIV-1 infection (PHI) would predict clinical progression and viral replication following ART. We measured HIV-1 DNA in a highly characterised randomised population of individuals with PHI. We explored associations between HIV-1 DNA and immunological and virological markers of clinical progression, including viral rebound in those interrupting therapy. In multivariable analyses, HIV-1 DNA was more predictive of disease progression than plasma viral load and, at treatment interruption, predicted time to plasma virus rebound. HIV-1 DNA may help identify individuals who could safely interrupt ART in future HIV-1 eradication trials. Clinical trial registration: ISRCTN76742797 and EudraCT2004-000446-20 DOI: http://dx.doi.org/10.7554/eLife.03821.001 PMID:25217531

  2. Raltegravir cerebrospinal fluid concentrations in HIV-1 infection.

    Directory of Open Access Journals (Sweden)

    Aylin Yilmaz

    2009-09-01

    Full Text Available Raltegravir is an HIV-1 integrase inhibitor currently used in treatment-experienced HIV-1-infected patients resistant to other drug classes. In order to assess its central nervous system penetration, we measured raltegravir concentrations in cerebrospinal fluid (CSF and plasma in subjects receiving antiretroviral treatment regimens containing this drug.Raltegravir concentrations were determined by liquid chromatography tandem mass spectrometry in 25 paired CSF and plasma samples from 16 HIV-1-infected individuals. The lower limit of quantitation was 2.0 ng/ml for CSF and 10 ng/ml for plasma.Twenty-four of the 25 CSF samples had detectable raltegravir concentrations with a median raltegravir concentration of 18.4 ng/ml (range, <2.0-126.0. The median plasma raltegravir concentration was 448 ng/ml (range, 37-5180. CSF raltegravir concentrations correlated with CSF:plasma albumin ratios and CSF albumin concentrations.Approximately 50% of the CSF specimens exceeded the IC(95 levels reported to inhibit HIV-1 strains without resistance to integrase inhibitors. In addition to contributing to control of systemic HIV-1 infection, raltegravir achieves local inhibitory concentrations in CSF in most, but not all, patients. Blood-brain and blood-CSF barriers likely restrict drug entry, while enhanced permeability of these barriers enhances drug entry.

  3. Raltegravir cerebrospinal fluid concentrations in HIV-1 infection.

    Science.gov (United States)

    Yilmaz, Aylin; Gisslén, Magnus; Spudich, Serena; Lee, Evelyn; Jayewardene, Anura; Aweeka, Francesca; Price, Richard W

    2009-09-01

    Raltegravir is an HIV-1 integrase inhibitor currently used in treatment-experienced HIV-1-infected patients resistant to other drug classes. In order to assess its central nervous system penetration, we measured raltegravir concentrations in cerebrospinal fluid (CSF) and plasma in subjects receiving antiretroviral treatment regimens containing this drug. Raltegravir concentrations were determined by liquid chromatography tandem mass spectrometry in 25 paired CSF and plasma samples from 16 HIV-1-infected individuals. The lower limit of quantitation was 2.0 ng/ml for CSF and 10 ng/ml for plasma. Twenty-four of the 25 CSF samples had detectable raltegravir concentrations with a median raltegravir concentration of 18.4 ng/ml (range, <2.0-126.0). The median plasma raltegravir concentration was 448 ng/ml (range, 37-5180). CSF raltegravir concentrations correlated with CSF:plasma albumin ratios and CSF albumin concentrations. Approximately 50% of the CSF specimens exceeded the IC(95) levels reported to inhibit HIV-1 strains without resistance to integrase inhibitors. In addition to contributing to control of systemic HIV-1 infection, raltegravir achieves local inhibitory concentrations in CSF in most, but not all, patients. Blood-brain and blood-CSF barriers likely restrict drug entry, while enhanced permeability of these barriers enhances drug entry.

  4. The Gut Microbiome and HIV-1 Pathogenesis: A Two Way Street

    Science.gov (United States)

    Dillon, Stephanie M.; Frank, Daniel N.; Wilson, Cara C.

    2016-01-01

    HIV-1 infection is associated with substantial damage to the gastrointestinal (GI) tract resulting in structural impairment of the epithelial barrier and a disruption of intestinal homeostasis. The accompanying translocation of microbial products and potentially microbes themselves from the lumen into systemic circulation has been linked to immune activation, inflammation, and HIV-1 disease progression. The importance of microbial translocation in the setting of HIV-1 infection has led to a recent focus on understanding how the communities of microbes that make up the intestinal microbiome are altered during HIV-1 infection and how they interact with mucosal immune cells to contribute to inflammation. This review details the dysbiotic intestinal communities associated with HIV-1 infection and their potential link to HIV-1 pathogenesis. We detail studies that begin to address the mechanisms driving microbiota-associated immune activation and inflammation and the various treatment strategies aimed at correcting dysbiosis and improving the overall health of HIV-1 infected individuals. Finally, we discuss how this relatively new field of research can advance to provide a more comprehensive understanding of the contribution of the gut microbiome to HIV-1 pathogenesis. PMID:27755100

  5. Uridine metabolism in HIV-1-infected patients: effect of infection, of antiretroviral therapy and of HIV-1/ART-associated lipodystrophy syndrome.

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    Pere Domingo

    Full Text Available BACKGROUND: Uridine has been advocated for the treatment of HIV-1/HAART-associated lipodystrophy (HALS, although its metabolism in HIV-1-infected patients is poorly understood. METHODS: Plasma uridine concentrations were measured in 35 controls and 221 HIV-1-infected patients and fat uridine in 15 controls and 19 patients. The diagnosis of HALS was performed following the criteria of the Lipodystrophy Severity Grading Scale. Uridine was measured by a binary gradient-elution HPLC method. Analysis of genes encoding uridine metabolizing enzymes in fat was performed with TaqMan RT-PCR. RESULTS: Median plasma uridine concentrations for HIV-1-infected patients were 3.80 µmol/l (interquartile range: 1.60, and for controls 4.60 µmol/l (IQR: 1.8 (P = 0.0009. In fat, they were of 6.0 (3.67, and 2.8 (4.65 nmol/mg of protein, respectively (P = 0.0118. Patients with a mixed HALS form had a median plasma uridine level of 4.0 (IC95%: 3.40-4.80 whereas in those with isolated lipoatrophy it was 3.25 (2.55-4.15 µmol/l/l (P = 0.0066. The expression of uridine cytidine kinase and uridine phosphorylase genes was significantly decreased in all groups of patients with respect to controls. A higher expression of the mRNAs for concentrative nucleoside transporters was found in HIV-1-infected patients with respect to healthy controls. CONCLUSIONS: HIV-1 infection is associated with a decrease in plasma uridine and a shift of uridine to the adipose tissue compartment. Antiretroviral therapy was not associated with plasma uridine concentrations, but pure lipoatrophic HALS was associated with significantly lower plasma uridine concentrations.

  6. A prospective study of the effect of pregnancy on CD4 counts and plasma HIV-1 RNA concentrations of antiretroviral-naive HIV-1 infected women

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    Heffron, Renee; Donnell, Deborah; Kiarie, James; Rees, Helen; Ngure, Kenneth; Mugo, Nelly; Were, Edwin; Celum, Connie; Baeten, Jared M.

    2014-01-01

    Background In HIV-1 infected women, CD4 count declines occur during pregnancy, which has been attributed to hemodilution. However, for women who have not initiated antiretroviral therapy (ART), it is unclear if CD4 declines are sustained beyond pregnancy and accompanied by increased viral levels, which could indicate an effect of pregnancy on accelerating HIV-1 disease progression. Methods In a prospective study among 2269 HIV-1 infected ART-naïve women from 7 African countries, we examined the effect of pregnancy on HIV-1 disease progression. We used linear mixed models to compare CD4 counts and plasma HIV-1 RNA concentrations between pregnant, postpartum and non-pregnant periods. Results Women contributed 3270 person-years of follow-up, during which time 476 women became pregnant. In adjusted analysis, CD4 counts were an average of 56 (95% CI 39-73) cells/mm3 lower during pregnant compared to non-pregnant periods and 70 (95% CI 53-88) cells/mm3 lower during pregnant compared to postpartum periods; these results were consistent when restricted to the subgroup of women who became pregnant. Plasma HIV-1 RNA concentrations were not different between pregnant and non-pregnant periods (p=0.9) or pregnant and postpartum periods (p=0.3). Neither CD4 counts nor plasma HIV-1 RNA levels were significantly different in postpartum compared to non-pregnant periods. Conclusion CD4 count declines among HIV-1 infected women during pregnancy are temporary and not sustained in postpartum periods. Pregnancy does not have a short term impact on plasma HIV-1 RNA concentrations. PMID:24442226

  7. Electron tomography of HIV-1 infection in gut-associated lymphoid tissue.

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    Ladinsky, Mark S; Kieffer, Collin; Olson, Gregory; Deruaz, Maud; Vrbanac, Vladimir; Tager, Andrew M; Kwon, Douglas S; Bjorkman, Pamela J

    2014-01-01

    Critical aspects of HIV-1 infection occur in mucosal tissues, particularly in the gut, which contains large numbers of HIV-1 target cells that are depleted early in infection. We used electron tomography (ET) to image HIV-1 in gut-associated lymphoid tissue (GALT) of HIV-1-infected humanized mice, the first three-dimensional ultrastructural examination of HIV-1 infection in vivo. Human immune cells were successfully engrafted in the mice, and following infection with HIV-1, human T cells were reduced in GALT. Virions were found by ET at all stages of egress, including budding immature virions and free mature and immature viruses. Immuno-electron microscopy verified the virions were HIV-1 and showed CD4 sequestration in the endoplasmic reticulum of infected cells. Observation of HIV-1 in infected GALT tissue revealed that most HIV-1-infected cells, identified by immunolabeling and/or the presence of budding virions, were localized to intestinal crypts with pools of free virions concentrated in spaces between cells. Fewer infected cells were found in mucosal regions and the lamina propria. The preservation quality of reconstructed tissue volumes allowed details of budding virions, including structures interpreted as host-encoded scission machinery, to be resolved. Although HIV-1 virions released from infected cultured cells have been described as exclusively mature, we found pools of both immature and mature free virions within infected tissue. The pools could be classified as containing either mostly mature or mostly immature particles, and analyses of their proximities to the cell of origin supported a model of semi-synchronous waves of virion release. In addition to HIV-1 transmission by pools of free virus, we found evidence of transmission via virological synapses. Three-dimensional EM imaging of an active infection within tissue revealed important differences between cultured cell and tissue infection models and furthered the ultrastructural understanding of

  8. Electron tomography of HIV-1 infection in gut-associated lymphoid tissue.

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    Mark S Ladinsky

    2014-01-01

    Full Text Available Critical aspects of HIV-1 infection occur in mucosal tissues, particularly in the gut, which contains large numbers of HIV-1 target cells that are depleted early in infection. We used electron tomography (ET to image HIV-1 in gut-associated lymphoid tissue (GALT of HIV-1-infected humanized mice, the first three-dimensional ultrastructural examination of HIV-1 infection in vivo. Human immune cells were successfully engrafted in the mice, and following infection with HIV-1, human T cells were reduced in GALT. Virions were found by ET at all stages of egress, including budding immature virions and free mature and immature viruses. Immuno-electron microscopy verified the virions were HIV-1 and showed CD4 sequestration in the endoplasmic reticulum of infected cells. Observation of HIV-1 in infected GALT tissue revealed that most HIV-1-infected cells, identified by immunolabeling and/or the presence of budding virions, were localized to intestinal crypts with pools of free virions concentrated in spaces between cells. Fewer infected cells were found in mucosal regions and the lamina propria. The preservation quality of reconstructed tissue volumes allowed details of budding virions, including structures interpreted as host-encoded scission machinery, to be resolved. Although HIV-1 virions released from infected cultured cells have been described as exclusively mature, we found pools of both immature and mature free virions within infected tissue. The pools could be classified as containing either mostly mature or mostly immature particles, and analyses of their proximities to the cell of origin supported a model of semi-synchronous waves of virion release. In addition to HIV-1 transmission by pools of free virus, we found evidence of transmission via virological synapses. Three-dimensional EM imaging of an active infection within tissue revealed important differences between cultured cell and tissue infection models and furthered the ultrastructural

  9. HIV-1 Nef in Macrophage-Mediated Disease Pathogenesis

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    Lamers, Susanna L.; Fogel, Gary B.; Singer, Elyse J.; Salemi, Marco; Nolan, David J.; Huysentruyt, Leanne C.; McGrath, Michael S.

    2013-01-01

    Combined anti-retroviral therapy (cART) has significantly reduced the number of AIDS-associated illnesses and changed the course of HIV-1 disease in developed countries. Despite the ability of cART to maintain high CD4+ T-cell counts, a number of macrophage-mediated diseases can still occur in HIV-infected subjects. These diseases include lymphoma, metabolic diseases, and HIV-associated neurological disorders. Within macrophages, the HIV-1 regulatory protein “Nef” can modulate surface receptors, interact with signaling pathways, and promote specific environments that contribute to each of these pathologies. Moreover, genetic variation in Nef may also guide the macrophage response. Herein, we review findings relating to the Nef–macrophage interaction and how this relationship contributes to disease pathogenesis. PMID:23215766

  10. Neuropsychological performance in patients with asymptomatic HIV-1 infection.

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    Martínez-Banfi, Martha; Vélez, Jorge I; Perea, M Victoria; García, Ricardo; Puentes-Rozo, Pedro J; Mebarak Chams, Moises; Ladera, Valentina

    2018-05-01

    Human immunodeficiency virus (HIV-1) infection and acquired immunodeficiency syndrome (AIDS) lead to neurocognitive disorders; however, there is still much knowledge to be gained regarding HIV-associated neurocognitive disorders. The purpose of this study was to assess the cognitive performance, instrumental activities of daily living, depression, and anxiety in patients with asymptomatic HIV-1 infections compared with seronegative participants without neurocognitive impairment. We studied a sample consisted of 60 patients with asymptomatic HIV-1 infections and 60 seronegative participants without neurocognitive impairment from the city of Barranquilla, Colombia, with a mean age of 36.07 years. A protocol of neuropsychological and psychopathological tests was applied to the participants. The group of patients with asymptomatic HIV infections significantly underperformed on tasks that assessed global cognitive screening, attention span, learning, phonemic verbal fluency, auditory-verbal comprehension, information processing speed, cognitive flexibility, and motor skills compared to the group of seronegative participants. No significant differences were found in memory, visual confrontation naming, vocabulary, inhibition, and instrumental activities of daily living. Additionally, the patients with asymptomatic HIV-1 infection had a higher anxiety index than the seronegative participants, but no significant difference was found in depression. A correlation was found between depression and anxiety. In conclusion, the patients with asymptomatic HIV-1 infection had lower cognitive performances than the seronegative participants in the cognitive functions mentioned above and more anxiety but still performed the instrumental activities of daily living.

  11. Molecular epidemiology of HIV-1 among the HIV infected people of Manipur, Northeastern India: Emergence of unique recombinant forms.

    Science.gov (United States)

    Sharma, Adhikarimayum Lakhikumar; Singh, Thiyam Ramsing; Devi, Khuraijam Ranjana; Singh, Lisam Shanjukumar

    2017-06-01

    According to the Joint National Programme on HIV/AIDS (UNAIDS), the northeastern region of India has the highest HIV prevalence in the country. This study was conducted to determine the current HIV-1 molecular epidemiology of Manipur, a state in northeast India. Blood samples from HIV-1 seropositive subjects were collected between June 2011 and February 2014. The partial regions of HIV-1 genes; pol and tat-vpu-env were independently amplified, sequenced, analyzed, and genotyped. Based on all sequences generated from 110 samples using pol and/or tat-vpu-env gene, the overall HIV-1 genotypes distribution of Manipur was as follows: 65.45% (72/110) subtype C, 32.73% (36/110) unique recombinant forms (URFs), and 1.82% (2/110) subtype B. The distribution of HIV-1 genotypes among the risk groups was: heterosexual: 58.33% (35/60) subtype C, 38.33% (23/60) URFs, and 3.34% (2/60) subtype B; intravenous drug users (IDUs): 85.36% (35/41) subtype C, 9.76% (4/41) URFs, and 4.88% (2/41) subtype B; mother to child (MTC): 50% (3/6) URFs and 50% (3/6) subtype C and blood transfusion: 100% (3/3) subtype C. The findings for the first time revealed the emergence of URFs of HIV-1 in Manipur which is predominant among the sexual and MTC risk groups as compared to IDUs. Taking together, this study illustrated that Manipur is the "recombinant hotspot of HIV" of India. The results will provide the clinical importance for continuous monitoring of HIV-infections in order to design appropriate prevention measures to limit the spread of new HIV infections. © 2016 Wiley Periodicals, Inc.

  12. Sexual practices of HIV-positive individuals attending antiretroviral treatment (ART) in Addis Ababa public hospitals: findings from in-depth interview.

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    Dessie, Yadeta; Deresa, Merga

    2012-01-01

    The rollout of Antiretroviral Treatment (ART) and improved health care services contributed in recuperating the quality of life and the functional status of HIV-positive people. These clinical effects of the treatment and cares are believed to bring a change on their sexual practices. The objective of this study was to explore the sexual practices of the HIV-positive people who were getting ART in selected Addis Ababa public hospitals. A qualitative in-depth interview was conducted. The interviews were made by trained nurse counselors of the same sex and were tape recorded. Verbatim transcription was made before the analysis. Thematic categorizations were made to present the findings. Most participants expressed regained sexual desires with initiation of ART while some others didn't appreciate the regains. Not using condoms or inconsistently using them was identified risky sexual practices. Sero-discordances and sero-status non-disclosure were common issues among the partners. Sero-status non-disclosure, non-use of condom and inconsistent using them were common sexual issues. These hinder the efforts that are being made to reduce new HIV infections and re-infections. Interventions against these problems can be made when clients come for their ART treatment and clinical care follow up.

  13. Potent inhibition of HIV-1 replication by a Tat mutant.

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    Luke W Meredith

    Full Text Available Herein we describe a mutant of the two-exon HIV-1 Tat protein, termed Nullbasic, that potently inhibits multiple steps of the HIV-1 replication cycle. Nullbasic was created by replacing the entire arginine-rich basic domain of wild type Tat with glycine/alanine residues. Like similarly mutated one-exon Tat mutants, Nullbasic exhibited transdominant negative effects on Tat-dependent transactivation. However, unlike previously reported mutants, we discovered that Nullbasic also strongly suppressed the expression of unspliced and singly-spliced viral mRNA, an activity likely caused by redistribution and thus functional inhibition of HIV-1 Rev. Furthermore, HIV-1 virion particles produced by cells expressing Nullbasic had severely reduced infectivity, a defect attributable to a reduced ability of the virions to undergo reverse transcription. Combination of these inhibitory effects on transactivation, Rev-dependent mRNA transport and reverse transcription meant that permissive cells constitutively expressing Nullbasic were highly resistant to a spreading infection by HIV-1. Nullbasic and its activities thus provide potential insights into the development of potent antiviral therapeutics that target multiple stages of HIV-1 infection.

  14. Vaginal Lactobacillus Inhibits HIV-1 Replication in Human Tissues Ex Vivo

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    Rogers A. Ñahui Palomino

    2017-05-01

    Full Text Available Lactobacillus species, which dominate vaginal microbiota of healthy reproductive-age women, lower the risks of sexually transmitted infections, including the risk of human immunodeficiency virus (HIV acquisition. The exact mechanisms of this protection remain to be understood. Here, we investigated these mechanisms in the context of human cervico-vaginal and lymphoid tissues ex vivo. We found that all six Lactobacillus strains tested in these systems significantly suppressed HIV type-1 (HIV-1 infection. We identified at least three factors that mediated this suppression: (i Acidification of the medium. The pH of the undiluted medium conditioned by lactobacilli was between 3.8 and 4.6. Acidification of the culture medium with hydrochloric acid (HCl to this pH in control experiments was sufficient to abrogate HIV-1 replication. However, the pH of the Lactobacillus-conditioned medium (CM diluted fivefold, which reached ∼6.9, was also suppressive for HIV-1 infection, while in control experiments HIV-1 infection was not abrogated when the pH of the medium was brought to 6.9 through the use of HCl. This suggested the existence of other factors responsible for HIV-1 inhibition by lactobacilli. (ii Lactic acid. There was a correlation between the concentration of lactic acid in the Lactobacillus-CM and its ability to suppress HIV-1 infection in human tissues ex vivo. Addition of lactic acid isomers D and L to tissue culture medium at the concentration that corresponded to their amount released by lactobacilli resulted in HIV-1 inhibition. Isomer L was produced in higher quantities than isomer D and was mostly responsible for HIV-1 inhibition. These results indicate that lactic acid, in particular its L-isomer, inhibits HIV-1 independently of lowering of the pH. (iii Virucidal effect. Incubation of HIV-1 in Lactobacillus-CM significantly suppressed viral infectivity for human tissues ex vivo. Finally, lactobacilli adsorb HIV-1, serving as a sink

  15. Phylodynamics of HIV-1 subtype F1 in Angola, Brazil and Romania.

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    Bello, Gonzalo; Afonso, Joana Morais; Morgado, Mariza G

    2012-07-01

    The HIV-1 subtype F1 is exceptionally prevalent in Angola, Brazil and Romania. The epidemiological context in which the spread of HIV occurred was highly variable from one country to another, mainly due to the existence of a long-term civil war in Angola and the contamination of a large number of children in Romania. Here we apply phylogenetic and Bayesian coalescent-based methods to reconstruct the phylodynamic patterns of HIV-1 subtype F1 in such different epidemiological settings. The phylogenetic analyses of HIV-1 subtype F1 pol sequences sampled worldwide confirmed that most sequences from Angola, Brazil and Romania segregated in country-specific monophyletic groups, while most subtype F1 sequences from Romanian children branched as a monophyletic sub-cluster (Romania-CH) nested within sequences from adults. The inferred time of the most recent common ancestor of the different subtype F1 clades were as follow: Angola=1983 (1978-1989), Brazil=1977 (1972-1981), Romania adults=1980 (1973-1987), and Romania-CH=1985 (1978-1989). All subtype F1 clades showed a demographic history best explained by a model of logistic population growth. Although the expansion phase of subtype F1 epidemic in Angola (mid 1980s to early 2000s) overlaps with the civil war period (1975-2002), the mean estimated growth rate of the Angolan F1 clade (0.49 year(-1)) was not exceptionally high, but quite similar to that estimated for the Brazilian (0.69 year(-1)) and Romanian adult (0.36 year(-1)) subtype F1 clades. The Romania-CH subtype F1 lineage, by contrast, displayed a short and explosive dissemination phase, with a median growth rate (2.47 year(-1)) much higher than that estimated for adult populations. This result supports the idea that the AIDS epidemic that affected the Romanian children was mainly caused by the spread of the HIV through highly efficient parenteral transmission networks, unlike adult populations where HIV is predominantly transmitted through sexual route. Copyright

  16. Infarto cerebral em duas crianças infectadas pelo HIV-1 Ischaemic stroke in two children with HIV-1

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    Cristiane Rocha

    2003-12-01

    Full Text Available Os quadros vasculares são incomuns não somente nos pacientes adultos (1% como também nas crianças. Nosso objetivo é alertar para a possibilidade da infecção pelo HIV-1 em crianças com manifestações cerebrovasculares. Das 204 crianças infectadas pelo HIV acompanhadas no Ambulatório de SIDA, descrevemos dois pacientes pré-escolares do gênero masculino, com quadro agudo febril, rebaixamento do nível de consciência, status epilepticus e hemiparesia como primeira manifestação de infecção pelo HIV-1. Nos dois casos evidenciou-se extensa isquemia em território da artéria cerebral média. Um dos pacientes evoluiu com tetraparesia espástica grave, sem contactuar com o meio, epilepsia parcial e óbito 4 anos após o diagnóstico, sem melhora do quadro neurológico. O outro paciente apresentou hemiparesia direita e afasia global, evoluindo com regressão completa do quadro neurológico. A infreqüência desses achados torna importante o seu relato, visando a inclusão da infecção pelo HIV-1 no diagnóstico diferencial das quadros cerebrovasculares na criança.Cerebral ischaemia caused by inflammatory vasculopathies has been described as a complication of human immunodeficiency virus (HIV infection. The goal of our study is to report two cases of pediatric human immunodeficiency virus infection and cerebrovascular manifestations. We describe two pre-school boys, from a group of 204 outpatients, who presented fever, seizures, hemiparesis and impairment of conscience level as a first symptom of HIV-1 infection. The serial imaging studies revealed infarction of middle cerebral artery in both cases. The first one child had a severe spastic tetraparesis and partial epilepsy and died four years later without any improvement despite of the antiretroviral therapy. The second patient had a right hemiparesis and global aphasia totally recovered two years later with antiretroviral and rehabilitation therapies. HIV infection should be included

  17. P2X1 Receptor Antagonists Inhibit HIV-1 Fusion by Blocking Virus-Coreceptor Interactions.

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    Giroud, Charline; Marin, Mariana; Hammonds, Jason; Spearman, Paul; Melikyan, Gregory B

    2015-09-01

    HIV-1 Env glycoprotein-mediated fusion is initiated upon sequential binding of Env to CD4 and the coreceptor CXCR4 or CCR5. Whereas these interactions are thought to be necessary and sufficient to promote HIV-1 fusion, other host factors can modulate this process. Previous studies reported potent inhibition of HIV-1 fusion by selective P2X1 receptor antagonists, including NF279, and suggested that these receptors play a role in HIV-1 entry. Here we investigated the mechanism of antiviral activity of NF279 and found that this compound does not inhibit HIV-1 fusion by preventing the activation of P2X1 channels but effectively blocks the binding of the virus to CXCR4 or CCR5. The notion of an off-target effect of NF279 on HIV-1 fusion is supported by the lack of detectable expression of P2X1 receptors in cells used in fusion experiments and by the fact that the addition of ATP or the enzymatic depletion of ATP in culture medium does not modulate viral fusion. Importantly, NF279 fails to inhibit HIV-1 fusion with cell lines and primary macrophages when added at an intermediate stage downstream of Env-CD4-coreceptor engagement. Conversely, in the presence of NF279, HIV-1 fusion is arrested downstream of CD4 binding but prior to coreceptor engagement. NF279 also antagonizes the signaling function of CCR5, CXCR4, and another chemokine receptor, as evidenced by the suppression of calcium responses elicited by specific ligands and by recombinant gp120. Collectively, our results demonstrate that NF279 is a dual HIV-1 coreceptor inhibitor that interferes with the functional engagement of CCR5 and CXCR4 by Env. Inhibition of P2X receptor activity suppresses HIV-1 fusion and replication, suggesting that P2X signaling is involved in HIV-1 entry. However, mechanistic experiments conducted in this study imply that P2X1 receptor is not expressed in target cells or involved in viral fusion. Instead, we found that inhibition of HIV-1 fusion by a specific P2X1 receptor antagonist, NF

  18. Determination of HIV-1 co-receptor usage.

    Science.gov (United States)

    Cavarelli, Mariangela; Scarlatti, Gabriella

    2014-01-01

    Human immunodeficiency virus type I (HIV-1) infects target cells through interaction with the CD4 molecule and chemokine receptors, mainly the β-chemokine receptor 5 (CCR5) and the α-chemokine receptor 4 (CXCR4). Viral isolates can be phenotypically classified based on the co-receptor they utilize to infect target cells. In this chapter, methods to determine the co-receptor usage of HIV-1 variants are described.

  19. Prevalence and social drivers of HIV among married and cohabitating heterosexual adults in south-eastern Tanzania: analysis of adult health community cohort data

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    Sally M. Mtenga

    2015-09-01

    Full Text Available Background: In sub-Saharan Africa, the prevalence of HIV among married and cohabiting couples is substantial. Information about the underlying social drivers of HIV transmission in couples is critical for the development of structural approaches to HIV prevention, but not readily available. We explored the association between social drivers, practices, and HIV status among stable couples in Ifakara, Tanzania. Design: Using a cross-sectional design, we analyzed data from a sample of 3,988 married or cohabiting individuals, aged 15 years and older from the MZIMA adult health community cohort study of 2013. Sociodemographic factors (sex, income, age, and education, gender norms (perceived acceptability for a wife to ask her partner to use a condom when she knows he is HIV positive, marriage characteristics (being in a monogamous or a polygamous marriage, being remarried, sexual behavior practices (lifetime number of sexual partners and concurrent sexual partners, health system factors (ever used voluntary HIV counseling and testing, and lifestyle patterns (alcohol use were used to explore the odds of being HIV positive, with 95% confidence intervals. Results: Prevalence of HIV/AIDS was 6.7% (5.9% males and 7.1% females. Gender norms, that is, perception that a woman is not justified to ask her husband to use a condom even when she knows he has a disease (adjusted odds ratio AOR=1.51, 95% CI 1.06–2.17, marital characteristics, that is, being remarried (AOR=1.49, 95% CI 1.08–2.04, and sexual behavior characteristics, that is, lifetime number of sexual partners (2–4: AOR=1.47, 95% CI 1.02–2.11; 5+: AOR=1.61, 95% CI 1.05–2.47 were the main independent predictors of HIV prevalence. Conclusions: Among married or cohabiting individuals, the key social drivers/practices that appeared to make people more vulnerable for HIV are gender norms, marriage characteristics (being remarried, and sexual behavior practices (lifetime number of sexual partners

  20. Still a hard-to-reach population? Using social media to recruit Latino gay couples for an HIV intervention adaptation study.

    Science.gov (United States)

    Martinez, Omar; Wu, Elwin; Shultz, Andrew Z; Capote, Jonathan; López Rios, Javier; Sandfort, Theo; Manusov, Justin; Ovejero, Hugo; Carballo-Dieguez, Alex; Chavez Baray, Silvia; Moya, Eva; López Matos, Jonathan; DelaCruz, Juan J; Remien, Robert H; Rhodes, Scott D

    2014-04-24

    Online social networking use has increased rapidly among African American and Latino men who have sex with men (MSM), making it important to understand how these technologies can be used to reach, retain, and maintain individuals in care and promote health wellness. In particular, the Internet is increasingly recognized as a platform for health communication and education. However, little is known about how primarily Spanish-speaking populations use and engage with each other through social media platforms. We aimed to recruit eligible couples for a study to adapt "Connect 'n Unite" (an HIV prevention intervention initially created for black gay couples) for Spanish-speaking Latino gay couples living in New York City. In order to successfully design and implement an effective social media recruitment campaign to reach Spanish-speaking Latino gay couples for our ongoing "Latinos en Pareja" study, our community stakeholders and research team used McGuire's communication/persuasion matrix. The matrix guided our research, specifically each marketing "channel", targeted "message", and target population or "receiver". We developed a social media recruitment protocol and trained our research staff and stakeholders to conduct social media recruitment. As a result, in just 1 month, we recruited all of our subjects (N=14 couples, that is, N=28 participants) and reached more than 35,658 participants through different channels. One of the major successes of our social media recruitment campaign was to build a strong stakeholder base that became involved early on in all aspects of the research process-from pilot study writing and development to recruitment and retention. In addition, the variety of "messages" used across different social media platforms (including Facebook, the "Latinos en Pareja" study website, Craigslist, and various smartphone applications such as Grindr, SCRUFF, and Jack'd) helped recruit Latino gay couples. We also relied on a wide range of community

  1. Six Highly Conserved Targets of RNAi Revealed in HIV-1-Infected Patients from Russia Are Also Present in Many HIV-1 Strains Worldwide.

    Science.gov (United States)

    Kretova, Olga V; Fedoseeva, Daria M; Gorbacheva, Maria A; Gashnikova, Natalya M; Gashnikova, Maria P; Melnikova, Nataliya V; Chechetkin, Vladimir R; Kravatsky, Yuri V; Tchurikov, Nickolai A

    2017-09-15

    RNAi has been suggested for use in gene therapy of HIV/AIDS, but the main problem is that HIV-1 is highly variable and could escape attack from the small interfering RNAs (siRNAs) due to even single nucleotide substitutions in the potential targets. To exhaustively check the variability in selected RNA targets of HIV-1, we used ultra-deep sequencing of six regions of HIV-1 from the plasma of two independent cohorts of patients from Russia. Six RNAi targets were found that are invariable in 82%-97% of viruses in both cohorts and are located inside the domains specifying reverse transcriptase (RT), integrase, vpu, gp120, and p17. The analysis of mutation frequencies and their characteristics inside the targets suggests a likely role for APOBEC3G (apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like 3G, A3G) in G-to-A mutations and a predominant effect of RT biases in the detected variability of the virus. The lowest frequency of mutations was detected in the central part of all six targets. We also discovered that the identical RNAi targets are present in many HIV-1 strains from many countries and from all continents. The data are important for both the understanding of the patterns of HIV-1 mutability and properties of RT and for the development of gene therapy approaches using RNAi for the treatment of HIV/AIDS. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  2. Comparison of substance use and risky sexual behavior among a diverse sample of urban, HIV-positive men who have sex with men

    Science.gov (United States)

    Hatfield, Laura A.; Horvath, Keith J.; Jacoby, Scott M.; Rosser, B. R. Simon

    2012-01-01

    Aims To measure substance use across racial and ethnic subgroups of HIV-positive men who have sex with men (MSM), model associations between drug use and unsafe sex, and characterize users of the substances most strongly associated with risky sexual behavior. Design Cross-sectional survey at the pre-intervention time point of the Positive Connections behavioral intervention trial. Setting HIV-positive men of color who have sex with men living in six US cities. Participants 675 trial participants. Measurements Self-reported drug and alcohol use and sexual behaviors. Findings We found high prevalence of substance use in this sample, with differences across racial and ethnic groups. Compared to Hispanic, African America, and men of other or mixed races/ethnicities, Caucasian men were most likely to report use of stimulants (30%), methamphetamines (27%), and amyl nitrite inhalants (“poppers”, 46%) with anal sex. African American men reported crack/cocaine use in the highest proportion (38%) among the four groups. While many drugs were individually associated with serodiscordant unprotected anal intercourse (SDUAI), only alcohol quantity and poppers with sex were retained in a multivariate model. More frequent poppers use was associated with more reported instances of SDUAI, adjusted for increased anal sex. Men who used poppers were more likely to be white, have completed more education, and have slightly higher income than non-users. Poppers users also reported lower peer norms and self-efficacy for condom use. In a multiple logistic regression model including these psychosocial factors, only poppers use (vs non-use OR = 2.46, CI: 1.55, 3.94) and condom self-efficacy (1 sd increase on scale OR = .58, CI: .46, .73) were significantly associated with SDUAI. Conclusion These results, from a large sample of HIV-positive MSM of color, highlight the HIV transmission importance of drugs used specifically in conjunction with sex. PMID:20155589

  3. Sexual risk taking among patients on antiretroviral therapy in an urban informal settlement in Kenya: a cross-sectional survey.

    Science.gov (United States)

    Ragnarsson, Anders; Ekström, Anna Mia; Carter, Jane; Ilako, Festus; Lukhwaro, Abigail; Marrone, Gaetano; Thorson, Anna

    2011-04-18

    Our intention was to analyze demographic and contextual factors associated with sexual risk taking among HIV-infected patients on antiretroviral treatment (ART) in Africa's largest informal urban settlement, Kibera in Nairobi, Kenya. We used a cross-sectional survey in a resource-poor, urban informal settlement in Nairobi; 515 consecutive adult patients on ART attending the African Medical and Research Foundation clinic in Kibera in Nairobi were included in the study. Interviewers used structured questionnaires covering socio-demographic characteristics, time on ART, number of sexual partners during the previous six months and consistency of condom use. Twenty-eight percent of patients reported inconsistent condom use. Female patients were significantly more likely than men to report inconsistent condom use (aOR 3.03; 95% CI 1.60-5.72). Shorter time on ART was significantly associated with inconsistent condom use. Multiple sexual partners were more common among married men than among married women (adjusted OR 4.38; 95% CI 1.82-10.51). Inconsistent condom use was especially common among women and patients who had recently started ART, i.e., when the risk of HIV transmission is higher. Having multiple partners was quite common, especially among married men, with the potential of creating sexual networks and an increased risk of HIV transmission. ART needs to be accompanied by other preventive interventions to reduce the risk of new HIV infections among sero-discordant couples and to increase overall community effectiveness.

  4. Cold denaturation of the HIV-1 protease monomer

    DEFF Research Database (Denmark)

    Rösner, Heike Ilona; Caldarini, Martina; Prestel, Andreas

    2017-01-01

    The HIV-1-protease is a complex protein which in its active form adopts a homodimer dominated by -sheet structures. We have discovered a cold-denatured state of the monomeric subunit of HIV-1-protease which is populated above 0ºC and therefore directly accessible to various spectroscopic approac...

  5. Alterations in HIV-1 LTR promoter activity during AIDS progression

    International Nuclear Information System (INIS)

    Hiebenthal-Millow, Kirsten; Greenough, Thomas C.; Bretttler, Doreen B.; Schindler, Michael; Wildum, Steffen; Sullivan, John L.; Kirchhoff, Frank

    2003-01-01

    HIV-1 variants evolving in AIDS patients frequently show increased replicative capacity compared to those present during early asymptomatic infection. It is known that late stage HIV-1 variants often show an expanded coreceptor tropism and altered Nef function. In the present study we investigated whether enhanced HIV-1 LTR promoter activity might also evolve during disease progression. Our results demonstrate increased LTR promoter activity after AIDS progression in 3 of 12 HIV-1-infected individuals studied. Further analysis revealed that multiple alterations in the U3 core-enhancer and in the transactivation-response (TAR) region seem to be responsible for the enhanced functional activity. Our findings show that in a subset of HIV-1-infected individuals enhanced LTR transcription contributes to the increased replicative potential of late stage virus isolates and might accelerate disease progression

  6. HIV-1 protease-substrate coevolution in nelfinavir resistance.

    Science.gov (United States)

    Kolli, Madhavi; Ozen, Ayşegül; Kurt-Yilmaz, Nese; Schiffer, Celia A

    2014-07-01

    Resistance to various human immunodeficiency virus type 1 (HIV-1) protease inhibitors (PIs) challenges the effectiveness of therapies in treating HIV-1-infected individuals and AIDS patients. The virus accumulates mutations within the protease (PR) that render the PIs less potent. Occasionally, Gag sequences also coevolve with mutations at PR cleavage sites contributing to drug resistance. In this study, we investigated the structural basis of coevolution of the p1-p6 cleavage site with the nelfinavir (NFV) resistance D30N/N88D protease mutations by determining crystal structures of wild-type and NFV-resistant HIV-1 protease in complex with p1-p6 substrate peptide variants with L449F and/or S451N. Alterations of residue 30's interaction with the substrate are compensated by the coevolving L449F and S451N cleavage site mutations. This interdependency in the PR-p1-p6 interactions enhances intermolecular contacts and reinforces the overall fit of the substrate within the substrate envelope, likely enabling coevolution to sustain substrate recognition and cleavage in the presence of PR resistance mutations. Resistance to human immunodeficiency virus type 1 (HIV-1) protease inhibitors challenges the effectiveness of therapies in treating HIV-1-infected individuals and AIDS patients. Mutations in HIV-1 protease selected under the pressure of protease inhibitors render the inhibitors less potent. Occasionally, Gag sequences also mutate and coevolve with protease, contributing to maintenance of viral fitness and to drug resistance. In this study, we investigated the structural basis of coevolution at the Gag p1-p6 cleavage site with the nelfinavir (NFV) resistance D30N/N88D protease mutations. Our structural analysis reveals the interdependency of protease-substrate interactions and how coevolution may restore substrate recognition and cleavage in the presence of protease drug resistance mutations. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

  7. Ectopic expression of anti-HIV-1 shRNAs protects CD8{sup +} T cells modified with CD4ζ CAR from HIV-1 infection and alleviates impairment of cell proliferation

    Energy Technology Data Exchange (ETDEWEB)

    Kamata, Masakazu, E-mail: masa3k@ucla.edu [Division of Hematology-Oncology, David Geffen School of Medicine at UCLA, Los Angeles, CA (United States); Kim, Patrick Y. [Department of Microbiology, Immunology, and Molecular Genetics, David Geffen School of Medicine at UCLA, Los Angeles, CA (United States); Ng, Hwee L. [Division of Infectious Diseases, David Geffen School of Medicine at UCLA, Los Angeles, CA (United States); Ringpis, Gene-Errol E.; Kranz, Emiko; Chan, Joshua; O' Connor, Sean [Department of Microbiology, Immunology, and Molecular Genetics, David Geffen School of Medicine at UCLA, Los Angeles, CA (United States); Yang, Otto O. [Department of Microbiology, Immunology, and Molecular Genetics, David Geffen School of Medicine at UCLA, Los Angeles, CA (United States); Division of Infectious Diseases, David Geffen School of Medicine at UCLA, Los Angeles, CA (United States); UCLA AIDS Institute, Los Angeles, CA (United States); AIDS Healthcare Foundation, Los Angeles, CA (United States); Chen, Irvin S.Y. [Division of Hematology-Oncology, David Geffen School of Medicine at UCLA, Los Angeles, CA (United States); Department of Microbiology, Immunology, and Molecular Genetics, David Geffen School of Medicine at UCLA, Los Angeles, CA (United States); UCLA AIDS Institute, Los Angeles, CA (United States)

    2015-07-31

    Chimeric antigen receptors (CARs) are artificially engineered receptors that confer a desired specificity to immune effector T cells. As an HIV-1-specific CAR, CD4ζ CAR has been extensively tested in vitro as well as in clinical trials. T cells modified with this CAR mediated highly potent anti-HIV-1 activities in vitro and were well-tolerated in vivo, but exerted limited effects on viral load and reservoir size due to poor survival and/or functionality of the transduced cells in patients. We hypothesize that ectopic expression of CD4ζ on CD8{sup +} T cells renders them susceptible to HIV-1 infection, resulting in poor survival of those cells. To test this possibility, highly purified CD8{sup +} T cells were genetically modified with a CD4ζ-encoding lentiviral vector and infected with HIV-1. CD8{sup +} T cells were vulnerable to HIV-1 infection upon expression of CD4ζ as evidenced by elevated levels of p24{sup Gag} in cells and culture supernatants. Concurrently, the number of CD4ζ-modified CD8{sup +} T cells was reduced relative to control cells upon HIV-1 infection. To protect these cells from HIV-1 infection, we co-expressed two anti-HIV-1 shRNAs previously developed by our group together with CD4ζ. This combination vector was able to suppress HIV-1 infection without impairing HIV-1-dependent effector activities of CD4ζ. In addition, the number of CD4ζ-modified CD8{sup +} T cells maintained similar levels to that of the control even under HIV-1 infection. These results suggest that protecting CD4ζ-modified CD8{sup +} T cells from HIV-1 infection is required for prolonged HIV-1-specific immune surveillance. - Highlights: • Ectopic expression of CD4ζ CAR in CD8{sup +} T cells renders them susceptible to HIV-1 infection. • Co-expression of two anti-HIV-1 shRNAs protects CD4ζ CAR-modified CD8{sup +} T cells from HIV-1 infection. • Protecting CD4ζ CAR-modified CD8{sup +} T cells from HIV-1 infection suppresses its cytopathic effect.

  8. HIV-1 incorporates and proteolytically processes human NDR1 and NDR2 serine-threonine kinases

    International Nuclear Information System (INIS)

    Devroe, Eric; Silver, Pamela A.; Engelman, Alan

    2005-01-01

    Mammalian genomes encode two related serine-threonine kinases, nuclear Dbf2 related (NDR)1 and NDR2, which are homologous to the Saccharomyces cerevisiae Dbf2 kinase. Recently, a yeast genetic screen implicated the Dbf2 kinase in Ty1 retrotransposition. Since several virion-incorporated kinases regulate the infectivity of human immunodeficiency virus type 1 (HIV-1), we speculated that the human NDR1 and NDR2 kinases might play a role in the HIV-1 life cycle. Here we show that the NDR1 and NDR2 kinases were incorporated into HIV-1 particles. Furthermore, NDR1 and NDR2 were cleaved by the HIV-1 protease (PR), both within virions and within producer cells. Truncation at the PR cleavage site altered NDR2 subcellular localization and inhibited NDR1 and NDR2 enzymatic activity. These studies identify two new virion-associated host cell enzymes and suggest a novel mechanism by which HIV-1 alters the intracellular environment of human cells

  9. Rare HIV-1 Subtype J Genomes and a New H/U/CRF02_AG Recombinant Genome Suggests an Ancient Origin of HIV-1 in Angola.

    Science.gov (United States)

    Bártolo, Inês; Calado, Rita; Borrego, Pedro; Leitner, Thomas; Taveira, Nuno

    2016-08-01

    Angola has an extremely diverse HIV-1 epidemic fueled in part by the frequent interchange of people with the Democratic Republic of Congo (DRC) and Republic of Congo (RC). Characterization of HIV-1 strains circulating in Angola should help to better understand the origin of HIV-1 subtypes and recombinant forms and their transmission dynamics. In this study we characterize the first near full-length HIV-1 genomic sequences from HIV-1 infected individuals from Angola. Samples were obtained in 1993 from three HIV-1 infected patients living in Cabinda, Angola. Near full-length genomic sequences were obtained from virus isolates. Maximum likelihood phylogenetic tree inference and analyses of potential recombination patterns were performed to evaluate the sequence classifications and origins. Phylogenetic and recombination analyses revealed that one virus was a pure subtype J, another mostly subtype J with a small uncertain region, and the final virus was classified as a H/U/CRF02_AG recombinant. Consistent with their epidemiological data, the subtype J sequences were more closely related to each other than to other J sequences previously published. Based on the env gene, taxa from Angola occur throughout the global subtype J phylogeny. HIV-1 subtypes J and H are present in Angola at low levels since at least 1993. Low transmission efficiency and/or high recombination potential may explain their limited epidemic success in Angola and worldwide. The high diversity of rare subtypes in Angola suggests that Angola was part of the early establishment of the HIV-1 pandemic.

  10. Potent nonnucleoside reverse transcriptase inhibitors target HIV-1 Gag-Pol.

    Directory of Open Access Journals (Sweden)

    Anna Figueiredo

    2006-11-01

    Full Text Available Nonnucleoside reverse transcriptase inhibitors (NNRTIs target HIV-1 reverse transcriptase (RT by binding to a pocket in RT that is close to, but distinct, from the DNA polymerase active site and prevent the synthesis of viral cDNA. NNRTIs, in particular, those that are potent inhibitors of RT polymerase activity, can also act as chemical enhancers of the enzyme's inter-subunit interactions. However, the consequences of this chemical enhancement effect on HIV-1 replication are not understood. Here, we show that the potent NNRTIs efavirenz, TMC120, and TMC125, but not nevirapine or delavirdine, inhibit the late stages of HIV-1 replication. These potent NNRTIs enhanced the intracellular processing of Gag and Gag-Pol polyproteins, and this was associated with a decrease in viral particle production from HIV-1-transfected cells. The increased polyprotein processing is consistent with premature activation of the HIV-1 protease by NNRTI-enhanced Gag-Pol multimerization through the embedded RT sequence. These findings support the view that Gag-Pol multimerization is an important step in viral assembly and demonstrate that regulation of Gag-Pol/Gag-Pol interactions is a novel target for small molecule inhibitors of HIV-1 production. Furthermore, these drugs can serve as useful probes to further understand processes involved in HIV-1 particle assembly and maturation.

  11. HIV Drug Resistance-Associated Mutations in Antiretroviral Naïve HIV-1-Infected Latin American Children

    Directory of Open Access Journals (Sweden)

    Luis E. Soto-Ramirez

    2010-01-01

    Full Text Available Our goal was to describe the presence of HIV drug resistance among HIV-1-infected, antiretroviral (ARV naïve children and adolescents in Latin America and to examine resistance in these children in relation to drug exposure in the mother. Genotyping was performed on plasma samples obtained at baseline from HIV-1-infected participants in a prospective cohort study in Brazil, Argentina, and Mexico (NISDI Pediatric Study. Of 713 HIV-infected children enrolled, 69 were ARV naïve and eligible for the analysis. At enrollment, mean age was 7.3 years; 81.2% were infected with HIV perinatally. Drug resistance mutations (DRMs were detected in 6 (8.7%; 95% confidence interval 3.1–18.2% ARV-naïve subjects; none of the mothers of these 6 received ARVs during their pregnancies and none of the children received ARV prophylaxis. Reverse transcriptase mutations K70R and K70E were detected in 3 and 2 subjects, respectively; protease mutation I50 V was detected in 1 subject. Three of the 6 children with DRMs initiated ARV therapy during followup, with a good response in 2. The overall rate of primary drug resistance in this pediatric HIV-infected population was low, and no subjects had more than 1 DRM. Mutations associated with resistance to nucleoside reverse transcriptase inhibitors were the most prevalent.

  12. The effects of beliefs about AIDS-related death on quality of life in Chinese married couples with both husband and wife infected with HIV: examining congruence using the actor-partner interdependence model.

    Science.gov (United States)

    Yu, Nancy Xiaonan

    2017-06-17

    This cross-sectional study examined the actor and partner effects of beliefs about AIDS-related death on quality of life in Chinese married couples in which both were living with HIV. A total of 49 married couples in central China who were both infected with HIV completed measures to assess their beliefs about AIDS-related death and quality of life. In the actor-partner interdependence model, the husband-wife dyad showed congruence in their beliefs about AIDS-related death (r = .40) and quality of life-mental health summary (r = .31), respectively, within the couple. Both actor and partner effects of beliefs about AIDS-related death on the quality of life-mental health summary, rather than the quality of life-physical health summary, were significant within the husband-wife dyad. Our findings indicate the dyadic interdependence of beliefs about AIDS-related death and the quality of life-mental health summary in married couples. Psychosocial interventions that target a reduction of negative death beliefs and enhancement of well-being in the context of HIV should treat the couple as a unit.

  13. HIV-1 subtype A gag variability and epitope evolution.

    Science.gov (United States)

    Abidi, Syed Hani; Kalish, Marcia L; Abbas, Farhat; Rowland-Jones, Sarah; Ali, Syed

    2014-01-01

    The aim of this study was to examine the course of time-dependent evolution of HIV-1 subtype A on a global level, especially with respect to the dynamics of immunogenic HIV gag epitopes. We used a total of 1,893 HIV-1 subtype A gag sequences representing a timeline from 1985 through 2010, and 19 different countries in Africa, Europe and Asia. The phylogenetic relationship of subtype A gag and its epidemic dynamics was analysed through a Maximum Likelihood tree and Bayesian Skyline plot, genomic variability was measured in terms of G → A substitutions and Shannon entropy, and the time-dependent evolution of HIV subtype A gag epitopes was examined. Finally, to confirm observations on globally reported HIV subtype A sequences, we analysed the gag epitope data from our Kenyan, Pakistani, and Afghan cohorts, where both cohort-specific gene epitope variability and HLA restriction profiles of gag epitopes were examined. The most recent common ancestor of the HIV subtype A epidemic was estimated to be 1956 ± 1. A period of exponential growth began about 1980 and lasted for approximately 7 years, stabilized for 15 years, declined for 2-3 years, then stabilized again from about 2004. During the course of evolution, a gradual increase in genomic variability was observed that peaked in 2005-2010. We observed that the number of point mutations and novel epitopes in gag also peaked concurrently during 2005-2010. It appears that as the HIV subtype A epidemic spread globally, changing population immunogenetic pressures may have played a role in steering immune-evolution of this subtype in new directions. This trend is apparent in the genomic variability and epitope diversity of HIV-1 subtype A gag sequences.

  14. HIV-1 subtype A gag variability and epitope evolution.

    Directory of Open Access Journals (Sweden)

    Syed Hani Abidi

    Full Text Available OBJECTIVE: The aim of this study was to examine the course of time-dependent evolution of HIV-1 subtype A on a global level, especially with respect to the dynamics of immunogenic HIV gag epitopes. METHODS: We used a total of 1,893 HIV-1 subtype A gag sequences representing a timeline from 1985 through 2010, and 19 different countries in Africa, Europe and Asia. The phylogenetic relationship of subtype A gag and its epidemic dynamics was analysed through a Maximum Likelihood tree and Bayesian Skyline plot, genomic variability was measured in terms of G → A substitutions and Shannon entropy, and the time-dependent evolution of HIV subtype A gag epitopes was examined. Finally, to confirm observations on globally reported HIV subtype A sequences, we analysed the gag epitope data from our Kenyan, Pakistani, and Afghan cohorts, where both cohort-specific gene epitope variability and HLA restriction profiles of gag epitopes were examined. RESULTS: The most recent common ancestor of the HIV subtype A epidemic was estimated to be 1956 ± 1. A period of exponential growth began about 1980 and lasted for approximately 7 years, stabilized for 15 years, declined for 2-3 years, then stabilized again from about 2004. During the course of evolution, a gradual increase in genomic variability was observed that peaked in 2005-2010. We observed that the number of point mutations and novel epitopes in gag also peaked concurrently during 2005-2010. CONCLUSION: It appears that as the HIV subtype A epidemic spread globally, changing population immunogenetic pressures may have played a role in steering immune-evolution of this subtype in new directions. This trend is apparent in the genomic variability and epitope diversity of HIV-1 subtype A gag sequences.

  15. Dolutegravir reshapes the genetic diversity of HIV-1 reservoirs.

    Science.gov (United States)

    Gantner, Pierre; Lee, Guinevere Q; Rey, David; Mesplede, Thibault; Partisani, Marialuisa; Cheneau, Christine; Beck-Wirth, Geneviève; Faller, Jean-Pierre; Mohseni-Zadeh, Mahsa; Martinot, Martin; Wainberg, Mark A; Fafi-Kremer, Samira

    2018-04-01

    Better understanding of the dynamics of HIV reservoirs under ART is a critical step to achieve a functional HIV cure. Our objective was to assess the genetic diversity of archived HIV-1 DNA over 48 weeks in blood cells of individuals starting treatment with a dolutegravir-based regimen. Eighty blood samples were prospectively and longitudinally collected from 20 individuals (NCT02557997) including: acutely (n = 5) and chronically (n = 5) infected treatment-naive individuals, as well as treatment-experienced individuals who switched to a dolutegravir-based regimen and were either virologically suppressed (n = 5) or had experienced treatment failure (n = 5). The integrase and V3 loop regions of HIV-1 DNA isolated from PBMCs were analysed by pyrosequencing at baseline and weeks 4, 24 and 48. HIV-1 genetic diversity was calculated using Shannon entropy. All individuals achieved or maintained viral suppression throughout the study. A low and stable genetic diversity of archived HIV quasispecies was observed in individuals starting treatment during acute infection. A dramatic reduction of the genetic diversity was observed at week 4 of treatment in the other individuals. In these patients and despite virological suppression, a recovery of the genetic diversity of the reservoirs was observed up to 48 weeks. Viral variants bearing dolutegravir resistance-associated substitutions at integrase position 50, 124, 230 or 263 were detected in five individuals (n = 5/20, 25%) from all groups except those who were ART-failing at baseline. None of these substitutions led to virological failure. These data demonstrate that the genetic diversity of the HIV-1 reservoir is reshaped following the initiation of a dolutegravir-based regimen and strongly suggest that HIV-1 can continue to replicate despite successful treatment.

  16. N-terminally truncated POM121C inhibits HIV-1 replication.

    Directory of Open Access Journals (Sweden)

    Hideki Saito

    Full Text Available Recent studies have identified host cell factors that regulate early stages of HIV-1 infection including viral cDNA synthesis and orientation of the HIV-1 capsid (CA core toward the nuclear envelope, but it remains unclear how viral DNA is imported through the nuclear pore and guided to the host chromosomal DNA. Here, we demonstrate that N-terminally truncated POM121C, a component of the nuclear pore complex, blocks HIV-1 infection. This truncated protein is predominantly localized in the cytoplasm, does not bind to CA, does not affect viral cDNA synthesis, reduces the formation of 2-LTR and diminished the amount of integrated proviral DNA. Studies with an HIV-1-murine leukemia virus (MLV chimeric virus carrying the MLV-derived Gag revealed that Gag is a determinant of this inhibition. Intriguingly, mutational studies have revealed that the blockade by N-terminally-truncated POM121C is closely linked to its binding to importin-β/karyopherin subunit beta 1 (KPNB1. These results indicate that N-terminally-truncated POM121C inhibits HIV-1 infection after completion of reverse transcription and before integration, and suggest an important role for KPNB1 in HIV-1 replication.

  17. Long Term Follow-up of HIV-1 Exposed Children in Nairobi

    International Nuclear Information System (INIS)

    Ndinya-Achola, J.O; Datta, P.; Maitha, G.; Embree, J.E.; Kreiss, J.K.; Achola, P.S.; Holmes, K.K.; Plummer, F.A.

    1992-01-01

    Transmission of HIV-1 from an infected mother to her infant is the major route of transmission of this infection to children. In sub-Saharan Africa where heterosexual transmission of HIV is the commonest mode of spread, high prevalence of HIV infection in women of child bearing age is bound to lead to increased paediatric AIDS as a result of vertical transmission. In recognizing these epidemiological factors, the University of Nairobi HIV-1 Perinatal Transmission and Paediatric AIDS Project was initiated in 1986. Antenatal mothers attending Pumwani Maternity Hospital were enrolled during labour and screened for HIV-1 infection by ELISA. Those reacting positive were to participate in the study. An equal number of negative controls were also recruited. The mothers and babies of both groups were followed for varying periods over the next five years. A total of 360 babies born to HIV infected mothers and 360 babies born to HIV negative mothers were examined. The mortality rate observed in the HIV-1 exposed was substantially higher than that observed in controls (RR 2.8, 95% CI 1.3-6.1). Common causes of death among infected infants were pneumonia, measles, malaria, gastroenteritis, tuberculosis, and septicaemia. The five year survival was 85% among HIV infected children. Maternal risk factors associated with transmission were marital status, duration of sexual activity and the age of the first intercourse

  18. Long Term Follow-up of HIV-1 Exposed Children in Nairobi

    Energy Technology Data Exchange (ETDEWEB)

    Ndinya-Achola, J O; Datta, P; Maitha, G [Department of Microbiology, University of Nairobi, (Kenya); Embree, J E; Kreiss, J K; Achola, P S [Health Department, Nairobi City Commission, Nairobi, (Kenya); Holmes, K K [Dept. of Medicine, Harboview Medical Centre, University of Washington, Seattle (United States); Plummer, F A [Dept. of Medical Microbiology, University of Manitoba (Canada)

    1992-05-15

    Transmission of HIV-1 from an infected mother to her infant is the major route of transmission of this infection to children. In sub-Saharan Africa where heterosexual transmission of HIV is the commonest mode of spread, high prevalence of HIV infection in women of child bearing age is bound to lead to increased paediatric AIDS as a result of vertical transmission. In recognizing these epidemiological factors, the University of Nairobi HIV-1 Perinatal Transmission and Paediatric AIDS Project was initiated in 1986. Antenatal mothers attending Pumwani Maternity Hospital were enrolled during labour and screened for HIV-1 infection by ELISA. Those reacting positive were to participate in the study. An equal number of negative controls were also recruited. The mothers and babies of both groups were followed for varying periods over the next five years. A total of 360 babies born to HIV infected mothers and 360 babies born to HIV negative mothers were examined. The mortality rate observed in the HIV-1 exposed was substantially higher than that observed in controls (RR 2.8, 95% CI 1.3-6.1). Common causes of death among infected infants were pneumonia, measles, malaria, gastroenteritis, tuberculosis, and septicaemia. The five year survival was 85% among HIV infected children. Maternal risk factors associated with transmission were marital status, duration of sexual activity and the age of the first intercourse.

  19. Molecular and phylogenetic analysis of HIV-1 variants circulating in Italy

    Directory of Open Access Journals (Sweden)

    Sbreglia Costanza

    2008-10-01

    Full Text Available Abstract Objective The continuous identification of HIV-1 non-B subtypes and recombinant forms in Italy indicates the need of constant molecular epidemiology survey of genetic forms circulating and transmitted in the resident population. Methods The distribution of HIV-1 subtypes has been evaluated in 25 seropositive individuals residing in Italy, most of whom were infected through a sexual route during the 1995–2005 period. Each sample has been characterized by detailed molecular and phylogenetic analyses. Results 18 of the 25 samples were positive at HIV-1 PCR amplification. Three samples showed a nucleotide divergence compatible with a non-B subtype classification. The phylogenetic analysis, performed on both HIV-1 env and gag regions, confirms the molecular sub-typing prediction, given that 1 sample falls into the C subtype and 2 into the G subtype. The B subtype isolates show high levels of intra-subtype nucleotide divergence, compatible with a long-lasting epidemic and a progressive HIV-1 molecular diversification. Conclusion The Italian HIV-1 epidemic is still mostly attributable to the B subtype, regardless the transmission route, which shows an increasing nucleotide heterogeneity. Heterosexual transmission and the interracial blending, however, are slowly introducing novel HIV-1 subtypes. Therefore, a molecular monitoring is needed to follow the constant evolution of the HIV-1 epidemic.

  20. Interaction of the phospholipid scramblase 1 with HIV-1 Tat results in the repression of Tat-dependent transcription

    International Nuclear Information System (INIS)

    Kusano, Shuichi; Eizuru, Yoshito

    2013-01-01

    Highlights: •PLSCR1 specifically interacted with HIV-1 Tat in vitro and in vivo. •PLSCR1 repressed Tat-dependent transactivation of the HIV-1 LTR. •Suppression of PLSCR1 expression enhanced the levels of HIV-1 transcripts. •PLSCR1 reduced the nuclear localization of Tat. -- Abstract: Human phospholipid scramblase 1 (PLSCR1) is an interferon (IFN)-stimulated gene and possesses an IFN-mediated antiviral function. We show here that PLSCR1 directly interacts with human immunodeficiency virus type-1 (HIV-1) Tat. This interaction occurs both in vitro and in vivo through amino acids 160–250 of PLSCR1. Overexpression of PLSCR1 efficiently represses the Tat-dependent transactivation of the HIV-1 long terminal repeat (LTR) and reduces the nuclear translocation of Tat. In addition, shRNA-mediated suppression of endogenous PLSCR1 expression enhances the levels of gag mRNA in an HIV-1-infected T-cell line. These findings indicate that PLSCR1 negatively regulates the Tat-dependent transactivation of the HIV-1 LTR during HIV-1 infection