Intra-facility linkage of HIV-positive mothers and HIV-exposed babies into HIV chronic care: rural and urban experience in a resource limited setting.

Directory of Open Access Journals (Sweden)

Christine Mugasha

Full Text Available INTRODUCTION: Linkage of HIV-infected pregnant women to HIV care remains critical for improvement of maternal and child outcomes through prevention of maternal-to-child transmission of HIV (PMTCT and subsequent chronic HIV care. This study determined proportions and factors associated with intra-facility linkage to HIV care and Early Infant Diagnosis care (EID to inform strategic scale up of PMTCT programs. METHODS: A cross-sectional review of records was done at 2 urban and 3 rural public health care facilities supported by the Infectious Diseases Institute (IDI. HIV-infected pregnant mothers, identified through routine antenatal care (ANC and HIV-exposed babies were evaluated for enrollment in HIV clinics by 6 weeks post-delivery. RESULTS: Overall, 1,025 HIV-infected pregnant mothers were identified during ANC between January and June, 2012; 267/1,025 (26% in rural and 743/1,025 (74% in urban facilities. Of these 375/1,025 (37% were linked to HIV clinics [67/267(25% rural and 308/758(41% urban]. Of 636 HIV-exposed babies, 193 (30% were linked to EID. Linkage of mother-baby pairs to HIV chronic care and EID was 16% (101/636; 8/179 (4.5%] in rural and 93/457(20.3% in urban health facilities. Within rural facilities, ANC registration <28 weeks-of-gestation was associated with mothers' linkage to HIV chronic care [AoR, 2.0 95% CI, 1.1-3.7, p = 0.019] and mothers' multi-parity was associated with baby's linkage to EID; AoR 4.4 (1.3-15.1, p = 0.023. Stigma, long distance to health facilities and vertical PMTCT services affected linkage in rural facilities, while peer mothers, infant feeding services, long patient queues and limited privacy hindered linkage to HIV care in urban settings. CONCLUSION: Post-natal linkage of HIV-infected mothers to chronic HIV care and HIV-exposed babies to EID programs was low. Barriers to linkage to HIV care vary in urban and rural settings. We recommend targeted interventions to rapidly improve linkage to

HIV transmission in the dental setting and the HIV-infected oral health care professional: workshop 1C.

LENUS (Irish Health Repository)

Flint, S R

2011-04-01

This workshop addressed two important issues: first, the global evidence of HIV transmission from health care provider to patient and from patient to health care provider in the general health care environment and the dental practice setting; second, in the era of highly active antiretroviral therapy, whether oral health care professionals living with HIV pose a risk of transmission to their patients and whether standard infection control is adequate to protect both the patient and the oral health care professional in dental practice. The workshop culminated in a general discussion and the formulation of a consensus statement from the participating delegates, representing more than 30 countries, on the criteria under which an HIV-infected oral health care professional might practice dentistry without putting patients at risk. This consensus statement, the Beijing Declaration, was agreed nem con.

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

Feasibility and Field Performance of a Simultaneous Syphilis and HIV Point-of-Care Test Based Screening Strategy in at Risk Populations in Edmonton, Canada

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Joshua Bergman

2013-01-01

Full Text Available Few studies have evaluated the feasibility of delivering syphilis point-of-care (POC testing in outreach (nonclinical settings in resource rich countries. The objectives of the study were to evaluate the feasibility and diagnostic performance of performing both HIV and syphilis POC testing in outreach settings and to document new cases identified in the study population. 1,265 outreach testing visits were offered syphilis and HIV POC testing and 81.5% (n=1,031 consented to testing. In our population, the SD Bioline 3.0 Syphilis Test had a sensitivity of 85.3% [CI (68.9–95.0], specificity of 100.0% [CI (99.6–100.0], positive predictive value (PPV of 100.0% [CI (88.1–100.0], and negative predictive value (NPV of 99.5% [CI (98.9–99.8]. Test characteristics for the INSTI HIV-1/HIV-2 Antibody Test had a 100.0% sensitivity [CI (39.8–100.00], 99.8 specificity [CI (99.3–100], 66.7% PPV [CI (22.3–95.7], and 100.0% NPV [CI (99.6–100.0]. Four new cases of syphilis and four new HIV cases were diagnosed. In summary, at risk population seeking STI testing found POC tests to be acceptable, the POC tests performed well in outreach settings, and new cases of syphilis and HIV were identified and linked to treatment and care.

What’s new? Investigating risk factors for severe childhood malnutrition in a high HIV prevalence South African setting1

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SALOOJEE, HAROON; DE MAAYER, TIM; GARENNE, MICHEL L.; KAHN, KATHLEEN

2010-01-01

Aim To identify risk factors for severe childhood malnutrition in a rural South African district with a high HIV/AIDS prevalence. Design Case-control study. Setting Bushbuckridge District, Limpopo Province, South Africa. Participants 100 children with severe malnutrition (marasmus, kwashiorkor, and marasmic kwashiorkor) were compared with 200 better nourished (>−2 SD weight-for-age) controls, matched by age and village of residence. Bivariate and multivariate analyses were conducted on a variety of biological and social risk factors. Results HIV status was known only for a minority of cases (39%), of whom 87% were HIV positive, while 45% of controls were stunted. In multivariate analysis, risk factors for severe malnutrition included suspicion of HIV in the family (parents or children) (OR 217.7, 95% CI 22.7–2091.3), poor weaning practices (OR 3.0, 95% CI 2.0–4.6), parental death (OR 38.0, 95% CI 3.8–385.3), male sex (OR 2.7, 95% CI 1.2–6.0), and higher birth order (third child or higher) (OR 2.3, 95% CI 1.0–5.1). Protective factors included a diverse food intake (OR 0.53, 95% CI 0.41–0.67) and receipt of a state child support grant (OR 0.44, 95% CI 0.20–0.97). A borderline association existed for family wealth (OR 0.9 per unit, 95% CI 0.83–1.0), father smoking marijuana (OR 3.9, 95% CI 1.1–14.5), and history of a pulmonary tuberculosis contact (OR 3.2, 95% CI 0.9–11.0). Conclusions Despite the increasing contribution of HIV to the development of severe malnutrition, traditional risk factors such as poor nutrition, parental disadvantage and illness, poverty, and social inequity remain important contributors to the prevalence of severe malnutrition. Interventions aiming to prevent and reduce severe childhood malnutrition in high HIV prevalence settings need to encompass the various dimensions of the disease: nutritional, economic, and social, and address the prevention and treatment of HIV/AIDS. PMID:17676510

Pilot Integration of HIV Screening and Healthcare Settings with Multi- Component Social Network and Partner Testing for HIV Detection.

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Rentz, Michael F; Ruffner, Andrew H; Ancona, Rachel M; Hart, Kimberly W; Kues, John R; Barczak, Christopher M; Lindsell, Christopher J; Fichtenbaum, Carl J; Lyons, Michael S

2017-11-23

Healthcare settings screen broadly for HIV. Public health settings use social network and partner testing ("Transmission Network Targeting (TNT)") to select high-risk individuals based on their contacts. HIV screening and TNT systems are not integrated, and healthcare settings have not implemented TNT. The study aimed to evaluate pilot implementation of multi-component, multi-venue TNT in conjunction with HIV screening by a healthcare setting. Our urban, academic health center implemented a TNT program in collaboration with the local health department for five months during 2011. High-risk or HIV positive patients of the infectious diseases clinic and emergency department HIV screening program were recruited to access social and partner networks via compensated peer-referral, testing of companions present with them, and partner notification services. Contacts became the next-generation index cases in a snowball recruitment strategy. The pilot TNT program yielded 485 HIV tests for 482 individuals through eight generations of recruitment with five (1.0%; 95% CI = 0.4%, 2.3%) new diagnoses. Of these, 246 (51.0%; 95% CI = 46.6%, 55.5%) reported that they had not been tested for HIV within the last 12 months and 383 (79.5%; 95% CI = 75.7%, 82.9%) had not been tested by the existing ED screening program within the last five years. TNT complements population screening by more directly targeting high-risk individuals and by expanding the population receiving testing. Information from existing healthcare services could be used to seed TNT programs, or TNT could be implemented within healthcare settings. Research evaluating multi-component, multi-venue HIV detection is necessary to maximize complementary approaches while minimizing redundancy. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

HIV/AIDS policy agenda setting in Iran

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Khodayari - Zarnaq, Rahim; Ravaghi, Hamid; Mohammad Mosaddeghrad, Ali; Sedaghat, Abbas; Mohraz, Minoo

2016-01-01

Background: HIV/AIDS control are one of the most important goals of the health systems. The aim of this study was to determine how HIV/AIDS control was initiated among policy makers’ agenda setting in Iran. Methods: A qualitative research (semi-structured interview) was conducted using Kingdon’s framework (problem, policy and politics streams, and policy windows and policy entrepreneurs) to analysis HIV/AIDS agenda setting in Iran. Thirty-two policy makers, managers, specialists, and researchers were interviewed. Also, 30 policy documents were analyzed. Framework analysis method was used for data analysis. Results: the increase of HIV among Injecting drug users (IDUs) and Female Sex Workers (FSWs), lack of control of their high-risk behaviors, and exceeding the HIV into concentrated phase were examples of problem stream. Policy stream was evidence-based solutions that highlighted the need for changing strategies for dealing with such a problem and finding technically feasible and acceptable solutions. Iran’s participation in United Nations General Assembly special sessions on HIV/AIDS (UNGASS), the establishment of National AIDS Committee; highlighting AIDS control in Iran’s five years development program and the support of the judiciary system of harm reduction policies were examples of politics stream. Policy entrepreneurs linking these streams put the HIV/AIDS on the national agenda (policy windows) and provide their solutions. Conclusion: There were mutual interactions among these three streams and sometimes, they weakened or reinforced each other. Future studies are recommended to understand the interactions between these streams’ parts and perhaps develop further Kingdon’s framework, especially in the health sector. PMID:27579283

Conflict and HIV: A framework for risk assessment to prevent HIV in conflict-affected settings in Africa.

Science.gov (United States)

Mock, Nancy B; Duale, Sambe; Brown, Lisanne F; Mathys, Ellen; O'maonaigh, Heather C; Abul-Husn, Nina Kl; Elliott, Sterling

2004-10-29

In sub-Saharan Africa, HIV/AIDS and violent conflict interact to shape population health and development in dramatic ways. HIV/AIDS can create conditions conducive to conflict. Conflict can affect the epidemiology of HIV/AIDS. Conflict is generally understood to accelerate HIV transmission, but this view is simplistic and disregards complex interrelationships between factors that can inhibit and accelerate the spread of HIV in conflict and post conflict settings, respectively. This paper provides a framework for understanding these factors and discusses their implications for policy formulation and program planning in conflict-affected settings.

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).

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

Opening the Door to Zero New HIV Infections in Closed Settings.

Science.gov (United States)

Torriente, Anna; Tadion, Alexander; Hsu, Lee-Nah

2016-06-01

Prisons and other closed settings are high-risk environments for HIV and tuberculosis (TB) transmission. Prisoners often experience overcrowded living conditions and violence-including sexual assault-increasing their vulnerability to HIV and TB. However, high infection rates in prisons affect both prisoners and prison employees. Both groups, in interacting with their families and their communities, represent a potential risk of HIV transmission outside the prison setting. National HIV and TB strategies should therefore include measures to prevent transmission and increase access to HIV-related services in prisons. Courts have progressively recognized the human rights of prisoners, including the right to health and access to HIV-related services. A number of national and regional court decisions have affirmed that prison authorities have a duty of care to prisoners and an obligation to ensure that prisoners have access to HIV prevention measures and treatment. Policies and programs on HIV, AIDS, and TB for prison workplaces that are aligned with the ILO's international labor standards can benefit both prisoners and prison employees. In particular, the ILO's HIV and AIDS Recommendation, 2010 (No. 200) affirms the principle of universal access to HIV services and provides guidance for the HIV/TB response in prison settings.

Conflict and HIV: A framework for risk assessment to prevent HIV in conflict-affected settings in Africa

Directory of Open Access Journals (Sweden)

Mock Nancy B

2004-10-01

Full Text Available Abstract In sub-Saharan Africa, HIV/AIDS and violent conflict interact to shape population health and development in dramatic ways. HIV/AIDS can create conditions conducive to conflict. Conflict can affect the epidemiology of HIV/AIDS. Conflict is generally understood to accelerate HIV transmission, but this view is simplistic and disregards complex interrelationships between factors that can inhibit and accelerate the spread of HIV in conflict and post conflict settings, respectively. This paper provides a framework for understanding these factors and discusses their implications for policy formulation and program planning in conflict-affected settings.

Acceleration of age-associated methylation patterns in HIV-1-infected adults.

Directory of Open Access Journals (Sweden)

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

Extended antiretroviral prophylaxis to reduce breast-milk HIV-1 transmission.

Science.gov (United States)

Kumwenda, Newton I; Hoover, Donald R; Mofenson, Lynne M; Thigpen, Michael C; Kafulafula, George; Li, Qing; Mipando, Linda; Nkanaunena, Kondwani; Mebrahtu, Tsedal; Bulterys, Marc; Fowler, Mary Glenn; Taha, Taha E

2008-07-10

Effective strategies are urgently needed to reduce mother-to-child transmission of human immunodeficiency virus type 1 (HIV-1) through breast-feeding in resource-limited settings. Women with HIV-1 infection who were breast-feeding infants were enrolled in a randomized, phase 3 trial in Blantyre, Malawi. At birth, the infants were randomly assigned to one of three regimens: single-dose nevirapine plus 1 week of zidovudine (control regimen) or the control regimen plus daily extended prophylaxis either with nevirapine (extended nevirapine) or with nevirapine plus zidovudine (extended dual prophylaxis) until the age of 14 weeks. Using Kaplan-Meier analyses, we assessed the risk of HIV-1 infection among infants who were HIV-1-negative on DNA polymerase-chain-reaction assay at birth. Among 3016 infants in the study, the control group had consistently higher rates of HIV-1 infection from the age of 6 weeks through 18 months. At 9 months, the estimated rate of HIV-1 infection (the primary end point) was 10.6% in the control group, as compared with 5.2% in the extended-nevirapine group (P<0.001) and 6.4% in the extended-dual-prophylaxis group (P=0.002). There were no significant differences between the two extended-prophylaxis groups. The frequency of breast-feeding did not differ significantly among the study groups. Infants receiving extended dual prophylaxis had a significant increase in the number of adverse events (primarily neutropenia) that were deemed to be possibly related to a study drug. Extended prophylaxis with nevirapine or with nevirapine and zidovudine for the first 14 weeks of life significantly reduced postnatal HIV-1 infection in 9-month-old infants. (ClinicalTrials.gov number, NCT00115648.) 2008 Massachusetts Medical Society

Longitudinal dynamics of the HIV-specific B cell response during intermittent treatment of primary HIV infection.

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Godelieve J de Bree

Full Text Available Neutralizing antibodies develop in natural HIV-1 infection. Their development often takes several years and may rely on chronic virus exposure. At the same time recent studies show that treatment early in infection may provide opportunities for immune preservation. However, it is unknown how intermittent treatment in early infection affects development of the humoral immune response over time. We investigate the effect of cART in early HIV infection on the properties of the memory B cell compartment following 6 months of cART or in the absence of treatment. The patients included participated in the Primo-SHM trial where patients with an early HIV-1 infection were randomized to no treatment or treatment for 24 or 60 weeks.Primo-SHM trial patients selected for the present study were untreated (n = 23 or treated for 24 weeks (n = 24. Here we investigate memory B cell properties at viral set-point and at a late time point (respectively median 54 and 73 weeks before (re-initiation of treatment.At viral set-point, the memory B cell compartment in treated patients demonstrated significantly lower fractions of antigen-primed, activated, memory B cells (p = 0.006. In contrast to untreated patients, in treated patients the humoral HIV-specific response reached a set point over time. At a transcriptional level, sets of genes that showed enhanced expression in memory B cells at viral setpoint in untreated patients, conversely showed rapid increase of expression of the same genes in treated patients at the late time point.These data suggest that, although the memory B cell compartment is phenotypically preserved until viral setpoint after treatment interruption, the development of the HIV-specific antibody response may benefit from exposure to HIV. The effect of viral exposure on B cell properties is also reflected by longitudinal changes in transcriptional profile in memory B cells over time in early treated patients.

Sensitivity and specificity of dried blood spots for HIV-1 viral load quantification

Science.gov (United States)

Pannus, Pieter; Claus, Maarten; Gonzalez, Maria Mercedes Perez; Ford, Nathan; Fransen, Katrien

2016-01-01

Abstract The use of dried blood spots (DBS) instead of plasma as a specimen type for HIV-1 viral load (VL) testing facilitates the decentralization of specimen collection and can increase access to VL testing in resource-limited settings. The performance of DBS for VL testing is lower, however, when compared to the gold standard sample type plasma. In this diagnostic accuracy study, we evaluated 3 VL assays with DBS. Participants were recruited between August 2012 and April 2015. Both plasma and DBS specimens were prepared and tested for HIV-1 VL with the Roche CAP/CTM HIV-1 test v2.0, the Abbott RealTime HIV-1, and the bioMérieux NucliSENS EasyQ HIV-1 v2.0. Sensitivity and specificity to detect treatment failure at a threshold of 1000 cps/mL with DBS were determined. A total of 272 HIV-positive patients and 51 HIV-negative people were recruited in the study. The mean difference or bias between plasma and DBS VL was 25% of the specimens differed by >0.5 log cps/mL. All 3 assays had comparable sensitivities around 80% and specificities around 90%. Upward misclassification rates were around 10%, but downward misclassification rates ranged from 20.3% to 23.6%. Differences in between assays were not statistically significant (P > 0.1). The 3 VL assays evaluated had suboptimal performance with DBS but still performed better than immunological or clinical monitoring. Even after the introduction of the much-anticipated point-of-care VL devices, it is expected that DBS will remain important as a complementary option for supporting access to VL monitoring, particularly in rural, resource-limited settings. Manufacturers should accelerate efforts to develop more reliable, sensitive and specific methods to test VL on DBS specimens. PMID:27902602

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

Implementation of Steiner point of fuzzy set.

Science.gov (United States)

Liang, Jiuzhen; Wang, Dejiang

2014-01-01

This paper deals with the implementation of Steiner point of fuzzy set. Some definitions and properties of Steiner point are investigated and extended to fuzzy set. This paper focuses on establishing efficient methods to compute Steiner point of fuzzy set. Two strategies of computing Steiner point of fuzzy set are proposed. One is called linear combination of Steiner points computed by a series of crisp α-cut sets of the fuzzy set. The other is an approximate method, which is trying to find the optimal α-cut set approaching the fuzzy set. Stability analysis of Steiner point of fuzzy set is also studied. Some experiments on image processing are given, in which the two methods are applied for implementing Steiner point of fuzzy image, and both strategies show their own advantages in computing Steiner point of fuzzy set.

Tracking the progress of HIV: the impact of point-of-care tests on antiretroviral therapy

Directory of Open Access Journals (Sweden)

Reid SD

2013-09-01

Full Text Available Steven D Reid, Sarah J Fidler, Graham S Cooke Department of Infectious Diseases, St Mary's Hospital, Imperial College London, London, UK Abstract: It is now around 30 years since the discovery of HIV, the virus that causes AIDS. More than 70 million people have been infected in that time and around 35 million have died. The majority of those currently living with HIV/AIDS are in low- and middle-income countries, with sub-Saharan Africa bearing a disproportionate burden of the global disease. In high-income countries, the introduction of antiretroviral therapy (ART has drastically reduced the morbidity and mortality associated with HIV. Patients on ART are now predicted to have near-normal life expectancy and the role of treatment is increasingly recognized in preventing new infections. In low- and middle-income countries, treatment is now more widely available and around half of those who need ART are currently receiving it. Early diagnosis of HIV is essential if ART is to be optimally implemented. Lab-based diagnostics for screening, diagnosis, treatment initiation, and the monitoring of treatment efficacy are critical in managing the disease and reducing the number of new infections each year. The introduction of point-of-care HIV rapid tests has transformed the epidemic, particularly in low- and middle-income countries. For the first time, these point-of-care tests allow for the rapid identification of infected individuals outside the laboratory who can undergo counseling and treatment and, in the case of pregnant women, allow the timely initiation of ART to reduce the risk of vertical transmission. Although survival is markedly improved with ART even in the absence of laboratory monitoring, long-term management of people living with HIV on ART, and their partners, is essential to ensure successful viral suppression. The burden of disease in many resource-poor settings with high HIV prevalence has challenged the ability of local laboratories

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.

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.

Analysing Music with Point-Set Compression Algorithms

DEFF Research Database (Denmark)

Meredith, David

2016-01-01

Several point-set pattern-discovery and compression algorithms designed for analysing music are reviewed and evaluated. Each algorithm takes as input a point-set representation of a score in which each note is represented as a point in pitch-time space. Each algorithm computes the maximal...... and sections in pieces of classical music. On the first task, the best-performing algorithms achieved success rates of around 84%. In the second task, the best algorithms achieved mean F1 scores of around 0.49, with scores for individual pieces rising as high as 0.71....

Opening the Door to Zero New HIV Infections in Closed Settings

OpenAIRE

Torriente, Anna; Tadion, Alexander; Hsu, Lee-Nah

2016-01-01

Abstract Prisons and other closed settings are high-risk environments for HIV and tuberculosis (TB) transmission. Prisoners often experience overcrowded living conditions and violence?including sexual assault?increasing their vulnerability to HIV and TB. However, high infection rates in prisons affect both prisoners and prison employees. Both groups, in interacting with their families and their communities, represent a potential risk of HIV transmission outside the prison setting. National HI...

Ecological association between HIV and concurrency point-prevalence in South Africa's ethnic groups.

Science.gov (United States)

Kenyon, Chris

2013-11-01

HIV prevalence between different ethnic groups within South Africa exhibits considerable variation. Numerous authors believe that elevated sexual partner concurrency rates are important in the spread of HIV. Few studies have, however, investigated if differential concurrency rates could explain differential HIV spread within ethnic groups in South Africa. This ecological analysis, explores how much of the variation in HIV prevalence by ethnic group is explained by differential concurrency rates. Using a nationally representative survey (the South African National HIV Prevalence, HIV Incidence, Behaviour and Communication Survey, 2005) the HIV prevalence in each of eight major ethnic groups was calculated. Linear regression analysis was used to assess the association between an ethnic group's HIV prevalence and the point-prevalence of concurrency. Results showed that HIV prevalence rates varied considerably between South Africa's ethnic groups. This applied to both different racial groups and to different ethnic groups within the black group. The point-prevalence of concurrency by ethnic group was strongly associated with HIV prevalence (R(2) = 0.83; p = 0.001). Tackling the key drivers of high HIV transmission in this population may benefit from more emphasis on partner reduction interventions.

The association of psychiatric disorders and HIV infection in the correctional setting.

Science.gov (United States)

Baillargeon, Jacques; Ducate, Suzanne; Pulvino, John; Bradshaw, Patrick; Murray, Owen; Olvera, Rene

2003-10-01

Psychiatric disorders, such as bipolar disorder, schizophrenia, and depression, have been associated with both HIV-associated risk behaviors and HIV infection. While the US prison population is reported to exhibit elevated rates of HIV/AIDS and most psychiatric disorders, scarce information currently exists on the association of these conditions in the prison setting. The present study examined the association of six major psychiatric disorders with HIV infection in one of the nation's largest prison populations. The study population consisted of 336,668 Texas Department of Criminal Justice inmates who were incarcerated for any duration between January 1, 1999 and December 31, 2001. Information on medical conditions and sociodemographic factors was obtained from an institution-wide medical information system. Inmates diagnosed with HIV infection exhibited elevated rates of major depression, dysthymia, bipolar disorder, schizophrenia, schizoaffective disorder, and non-schizophrenic psychotic disorder. These rates persisted in stratified analyses and in a multivariate analysis that statistically adjusted for gender, race, and age category. The present cross-sectional study's finding of a positive association between HIV infection and psychiatric diagnoses among inmates holds both clinical and public health relevance. It will be important for future investigations to prospectively assess the underlying mechanisms of these associations in the correctional setting.

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

An HIV1/2 point of care test on sputum for screening TB/HIV co-infection in central India - Will it work?

Institute of Scientific and Technical Information of China (English)

Prabha Desikan; Sajal De; Nitika Pant Pai; Pradyumna K Mishra; Kaushal Kumar; Nikita Panwalkar; Mayanka Verma; Zia Ul Hasan; Kewal K Maudar

2013-01-01

Objective:To determine whether theOraQuick®HIV-1/2Assay(OraSureTechnologies, Inc.,Bethlehem,PA,USA) in sputum is a valid tool forHIV surveillance amongTB patients. Methods:A cross sectional study was carried out on sputa of patients diagnosed with tuberculosis.Sputa were tested for antibodies toHIV usingOraQuick®HIV-1/2Assay(OraSure Technologies,Inc.,Bethlehem,PA,USA).The results were compared with results of serum ELISA.Results:Compared to serumELISA, theOraQuick®HIV-1/2Assay in sputum specimens reported90% sensitivity(9/10) and100% specificity(307/307), with a positive predictive value of 100%(95%CI:66.37%-100.00%) and a negative predictive value of99.68%(95%CI:98.20%-99.99%). Conclusions:This testing method may provide a useful strategy for conductingHIV surveillance in possible co-infectedTB patients at peripheral centres.Since there is no investment on infrastructure, it may be possible for paramedical health professionals to carry out the test, particularly in areas with lowHIV endemicity.

Geometric fit of a point set by generalized circles

DEFF Research Database (Denmark)

Körner, Mark-Christopher; Brimberg, Jack; Juel, Henrik

2010-01-01

In our paper we approximate a set of given points by a general circle. More precisely, given two norms k 1 and k 2 and a set of points in the plane, we consider the problem of locating and scaling the unit circle of norm k 1 such that the sum of weighted distances between the circumference...... of the circle and the given points is minimized, where the distance is measured by a norm k 2. We present results for the general case. In the case that k 1 and k 2 are both polyhedral norms, we are able to solve the problem by investigating a finite candidate set....

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...

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.

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.

Point-of-Care Virologic Testing to Improve Outcomes of HIV-Infected Children in Zambia: A Clinical Trial Protocol.

Science.gov (United States)

Chibwesha, Carla J; Ford, Catherine E; Mollan, Katie R; Stringer, Jeffrey S A

2016-08-01

In the absence of early infant diagnosis (EID) and immediate antiretroviral therapy (ART), some 50% of untreated HIV-infected infants die before age 2. Conventional EID requires sophisticated instruments that are typically placed in centralized or reference laboratories. In low-resource settings, centralized systems often lead to result turnaround times of several months, long delays in diagnosis, and adverse outcomes for HIV-infected children. Our clinical trial tests the effectiveness of a new point-of-care (POC) diagnostic technology to identify HIV-infected infants and start providing them life-saving ART as soon as possible. The study uses a randomized, controlled design to test whether the Alere q platform for HIV DNA polymerase chain reaction (PCR) testing improves outcomes of HIV-infected children in Zambia. We aim to enroll 2867 HIV-exposed infants aged 4-12 weeks and to follow those who are HIV infected for 12 months as they receive HIV care at 6 public health facilities in Lusaka. The trial's primary endpoint is the proportion of HIV-infected infants in each study arm who start ART and remain alive, in care, and virally suppressed 12 months after their diagnostic blood draw. Our trial will provide evidence for the incremental benefit of implementing a POC EID strategy in low-resource settings where only off-site PCR services are currently available. The results will be useful in guiding future decisions regarding investments in POC virologic testing as part of overall pediatric AIDS mitigation strategies in sub-Saharan Africa. clinicaltrials.gov NCT02682810.

Laboratory Evaluation of the Alere q Point-of-Care System for Early Infant HIV Diagnosis.

Science.gov (United States)

Hsiao, Nei-yuan; Dunning, Lorna; Kroon, Max; Myer, Landon

2016-01-01

Early infant diagnosis (EID) and prompt linkage to care are critical to minimise the high morbidity and mortality associated with infant HIV infection. Attrition in the "EID cascade" is common; however, point-of-care (POC) EID assays with same-day result could facilitate prompt linkage of HIV-infected infant to treatment. Despite a number of POC EID assays in development, few have been independently evaluated and data on new technologies are urgently needed to inform policy. We compared Alere q 1/2 Detect POC system laboratory test characteristics with the local standard of care (SOC), Roche CAP/CTM HIV-1 qualitative PCR in an independent laboratory-based evaluation in Cape Town, South Africa. Routinely EID samples collected between November 2013 and September 2014 were each tested by both SOC and POC systems. Repeat testing was done to troubleshoot any discrepancy between POC and SOC results. Overall, 1098 children with a median age of 47 days (IQR, 42-117) were included. Birth PCR (age laboratory. The high specificity and thus high positive predictive value would suggest a positive POC result may be adequate for immediate infant ART initiation. While POC testing for EID may have particular utility for birth testing at delivery facilities, the lower sensitivity and error rate requires further attention, as does field implementation of POC EID technologies in other clinical care settings.

HIV and Pregnancy in Resource-Poor Settings

Science.gov (United States)

Tang, Jennifer; Nour, Nawal M

2010-01-01

There are 33.4 million people living with human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome. Globally, HIV/AIDS is the leading cause of death among women of reproductive age. In the United States and other developed countries, aggressive efforts to treat HIV-positive pregnant women with highly active antiretroviral therapy have decreased the maternal-to-child transmission (MTCT) from over 20% to less than 2%. However, in resource-poor settings, access to antiretroviral therapy (ART) is not readily available, and perinatal transmission rates remain as high as 45%. Women are at greater risk of heterosexual transmission of HIV, which is compounded by lack of condom use, imbalance of social power, and the high fertility rate. Prevention programs are needed to empower and educate women and engender community awareness for condom use. Prenatal screening and treatment, intrapartum ART, and postpartum prophylaxis must be made available to all women and children to prevent MTCT. PMID:20842284

Impact of polymorphisms in the HCP5 and HLA-C, and ZNRD1 genes on HIV viral load

DEFF Research Database (Denmark)

Thørner, Lise Wegner; Erikstrup, Christian; Harritshøj, Lene Holm

2016-01-01

AIMS: Single nucleotide polymorphisms (SNPs) in the human leucocyte antigen (HLA) complex P5 (HCP5), HLA-C, and near the zinc ribbon domain containing 1 (ZNRD1) have been shown to influence viral load (VL) set point in HIV-infected individuals with a known seroconversion onset. We aimed to determ...

The association of neoplasms and HIV infection in the correctional setting.

Science.gov (United States)

Baillargeon, Jacques; Pollock, Brad H; Leach, Charles T; Gao, Shou-Jiang

2004-05-01

HIV-associated immunosuppression has been linked to an increased risk of a number of cancers, including Kaposi sarcoma (KS), non-Hodgkin's lymphoma (NHL), and invasive cervical cancer. Because prison inmates constitute one of the highest HIV/AIDS prevalent populations in the US, understanding the link between HIV infection and cancer in the correctional setting holds particular public health relevance. The study population consisted of 336,668 Texas Department of Criminal Justice inmates who were incarcerated, for any duration, between 1 January 1999 and 31 December 2001. Inmates diagnosed with HIV infection exhibited elevated rates of KS, NHL, anal cancer, and Hodgkin's disease, after adjusting for age and race. The elevated rates of cancer among HIV-infected individuals, particularly prison inmates, may be mediated, in part, by high-risk behaviours. HIV-associated risk behaviours, including unsafe sexual practices, injection drug use, and prostitution may be associated with cancer-related risk behaviours, such as smoking, excessive alcohol consumption, and poor diet. It will be important for future investigators to examine the association between HIV infection and cancer risk with sufficiently large study cohorts and appropriate longitudinal designs.

Human anti-HIV IgM detection by the OraQuick ADVANCE® Rapid HIV 1/2 Antibody Test.

Science.gov (United States)

Guillon, Geraldine; Yearwood, Graham; Snipes, Casey; Boschi, Daniel; Reed, Michael R

2018-01-01

The Centers for Disease Control and Prevention (CDC) and many public health jurisdictions continue to advocate for the most sensitive rapid HIV test that is available. Currently, the recommendation is to utilize tests that can detect HIV infection biomarkers within 30 days of infection, when initial immune responses are mounted. The infected patient's IgM response is often used to detect acute infection within a 20-25 days window after infection. This requirement applies to lab-based testing with automated analyzers and rapid, point of care (POC) testing used for screening in a non-clinical setting. A recent study has demonstrated that POC tests using a Protein A-based detection system can detect samples with predominantly HIV-1 IgM reactivity (Moshgabadi et al., 2015). The OraQuick ADVANCE ® Rapid HIV-1/2 Antibody Test (OraQuick ADVANCE ®) also uses Protein A as the detection protein in the antibody-binding colloidal gold conjugate, so it is expected that the OraQuick ADVANCE ® Test will also detect samples with predominantly IgM reactivity. This report definitively demonstrates that the OraQuick ADVANCE ® Test can detect IgM antibodies during an acute infection window period of approximately 20-25 days after infection, and is therefore suitable for use in testing environments requiring adherence to current CDC recommendations.

Testing initiatives increase rates of HIV diagnosis in primary care and community settings: an observational single-centre cohort study.

Directory of Open Access Journals (Sweden)

Prini Mahendran

Full Text Available The primary objective was to examine trends in new HIV diagnoses in a UK area of high HIV prevalence between 2000 and 2012 with respect to site of diagnosis and stage of HIV infection.Single-centre observational cohort study.An outpatient HIV department in a secondary care UK hospital.1359 HIV-infected adults.Demographic information (age, gender, ethnicity, and sexual orientation, site of initial HIV diagnosis (Routine settings such as HIV/GUM clinics versus Non-Routine settings such as primary care and community venues, stage of HIV infection, CD4 count and seroconversion symptoms were collated for each participant.There was a significant increase in the proportion of new HIV diagnoses made in Non-Routine settings (from 27.0% in 2000 to 58.8% in 2012; p<0.001. Overall there was a decrease in the rate of late diagnosis from 50.7% to 32.9% (p=0.001. Diagnosis of recent infection increased from 23.0% to 47.1% (p=0.001. Of those with recent infection, significantly more patients were likely to report symptoms consistent with a seroconversion illness over the 13 years (17.6% to 65.0%; p<0.001.This is the first study, we believe, to demonstrate significant improvements in HIV diagnosis and a shift in diagnosis of HIV from HIV/GUM settings to primary practice and community settings due to multiple initiatives.

Acquired Long QT Syndrome and Torsade de Pointes Associated with HIV Infection

Directory of Open Access Journals (Sweden)

Alexander Shimabukuro-Vornhagen

2010-01-01

Full Text Available Here, we report the case of an HIV infected patient that was treated for pneumonia with a macrolid antibiotic. The patient experienced a prolongation of the already pathologic QTc interval resulting in repeated torsades de pointes necessitating CPR and implantation of an AICD. This case exemplifies that torsades de pointes due to acquired long QT syndrome is a serious and potentially fatal complication in HIV-positive patients.

Determination of the protection set-points lines for the Angra-1 reactor core

International Nuclear Information System (INIS)

Furieri, E.B.

1980-03-01

In this work several thermo-hidraulic calculation were performed to obtain Protection set-points lines for the Angra-1 reactor core in order to compare with the values presented by the vendor in the FSAR. These lines are the locus of points where DNBR min = 1,3 and power = 1,18 x P nominal as a function of ΔT m and T m , the temperature difference and the average coolant temperature between hot and cold legs. A computation scheme was developed using COBRA-IIIF as a subroutine of a new main program and adding new subroutines in order to obtain the desired DNBR. The solution is obtained through a convergentce procedure using parameters estimated in a sensivity study. (author) [pt

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

DEPIVIH 2: Use of three HIV testing methods in French primary care settings - ELISA laboratory screening versus two rapid point-of-care HIV tests.

Science.gov (United States)

Papadima, D; Gauthier, R; Prévoteau du Clary, F; Bouée, S; Conort, G; Livrozet, J-M; Taulera, O; Wajsbrot, A; Majerholc, C; Peter, J-M; Aubert, J-P

2018-03-01

The primary endpoint was to evaluate the use of HIV testing methods by French primary care providers: Elisa laboratory screening, instant result HIV diagnostic test and rapid result HIV diagnostic test. The secondary endpoints were the population screening rate of unknown HIV status consulting during the study period, reasons for screening and for choosing the specific screening method, the investigators' satisfaction with the rapid diagnostic test (RDT) and problems encountered. National prospective interventional study with French family physicians (FP) from December 2013 to December 2014. FPs enrolled all consenting adults consulting for an HIV screening test during a 6-month period: the choice was an Elisa laboratory test or one of the two RDTs. During the study period, 43 FPs included 981 patients. HIV screening was performed for the first time for 31.6% of patients; 767 (78.2%) Elisa laboratory test prescriptions and 214 (21.8%) RDTs were performed, leading to a screening rate of 1.3%. For 120 (15.7%) of the Elisa laboratory tests, the result was not reported and six RDTs were not valid. Nine patients were diagnosed as HIV-infected (0.9%): five with Elisa laboratory test and four with RDT. Almost 90% of FPs were willing to keep on using RDTs in their daily practice. In general practice, RDTs may be an important additional tool to traditional HIV screening. They could account for one in five tests prescribed in this context. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

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.

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

Role of transmitted Gag CTL polymorphisms in defining replicative capacity and early HIV-1 pathogenesis.

Directory of Open Access Journals (Sweden)

Jessica L Prince

Full Text Available Initial studies of 88 transmission pairs in the Zambia Emory HIV Research Project cohort demonstrated that the number of transmitted HLA-B associated polymorphisms in Gag, but not Nef, was negatively correlated to set point viral load (VL in the newly infected partners. These results suggested that accumulation of CTL escape mutations in Gag might attenuate viral replication and provide a clinical benefit during early stages of infection. Using a novel approach, we have cloned gag sequences isolated from the earliest seroconversion plasma sample from the acutely infected recipient of 149 epidemiologically linked Zambian transmission pairs into a primary isolate, subtype C proviral vector, MJ4. We determined the replicative capacity (RC of these Gag-MJ4 chimeras by infecting the GXR25 cell line and quantifying virion production in supernatants via a radiolabeled reverse transcriptase assay. We observed a statistically significant positive correlation between RC conferred by the transmitted Gag sequence and set point VL in newly infected individuals (p = 0.02. Furthermore, the RC of Gag-MJ4 chimeras also correlated with the VL of chronically infected donors near the estimated date of infection (p = 0.01, demonstrating that virus replication contributes to VL in both acute and chronic infection. These studies also allowed for the elucidation of novel sites in Gag associated with changes in RC, where rare mutations had the greatest effect on fitness. Although we observed both advantageous and deleterious rare mutations, the latter could point to vulnerable targets in the HIV-1 genome. Importantly, RC correlated significantly (p = 0.029 with the rate of CD4+ T cell decline over the first 3 years of infection in a manner that is partially independent of VL, suggesting that the replication capacity of HIV-1 during the earliest stages of infection is a determinant of pathogenesis beyond what might be expected based on set point VL alone.

Laboratory Diagnosis Of Dual Hiv-1/Hiv-2 Infection In Ghanaian ...

African Journals Online (AJOL)

Objective: To determine the true prevalence of HIV dual infections in a previously characterised HIV seropositive patient group due to inconsistencies between different diagnostic methods. Design: A cross-sectional study of an HIV seropositive group with different diagnostic methods. Setting: Three hospitals in the Northern, ...

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...

Single Nucleotide Polymorphism in Gene Encoding Transcription Factor Prep1 Is Associated with HIV-1-Associated Dementia

Science.gov (United States)

van Manen, Daniëlle; Bunnik, Evelien M.; van Sighem, Ard I.; Sieberer, Margit; Boeser-Nunnink, Brigitte; de Wolf, Frank; Schuitemaker, Hanneke; Portegies, Peter; Kootstra, Neeltje A.; van 't Wout, Angélique B.

2012-01-01

Background Infection with HIV-1 may result in severe cognitive and motor impairment, referred to as HIV-1-associated dementia (HAD). While its prevalence has dropped significantly in the era of combination antiretroviral therapy, milder neurocognitive disorders persist with a high prevalence. To identify additional therapeutic targets for treating HIV-associated neurocognitive disorders, several candidate gene polymorphisms have been evaluated, but few have been replicated across multiple studies. Methods We here tested 7 candidate gene polymorphisms for association with HAD in a case-control study consisting of 86 HAD cases and 246 non-HAD AIDS patients as controls. Since infected monocytes and macrophages are thought to play an important role in the infection of the brain, 5 recently identified single nucleotide polymorphisms (SNPs) affecting HIV-1 replication in macrophages in vitro were also tested. Results The CCR5 wt/Δ32 genotype was only associated with HAD in individuals who developed AIDS prior to 1991, in agreement with the observed fading effect of this genotype on viral load set point. A significant difference in genotype distribution among all cases and controls irrespective of year of AIDS diagnosis was found only for a SNP in candidate gene PREP1 (p = 1.2×10−5). Prep1 has recently been identified as a transcription factor preferentially binding the −2,518 G allele in the promoter of the gene encoding MCP-1, a protein with a well established role in the etiology of HAD. Conclusion These results support previous findings suggesting an important role for MCP-1 in the onset of HIV-1-associated neurocognitive disorders. PMID:22347417

Single nucleotide polymorphism in gene encoding transcription factor Prep1 is associated with HIV-1-associated dementia.

Directory of Open Access Journals (Sweden)

Sebastiaan M Bol

Full Text Available BACKGROUND: Infection with HIV-1 may result in severe cognitive and motor impairment, referred to as HIV-1-associated dementia (HAD. While its prevalence has dropped significantly in the era of combination antiretroviral therapy, milder neurocognitive disorders persist with a high prevalence. To identify additional therapeutic targets for treating HIV-associated neurocognitive disorders, several candidate gene polymorphisms have been evaluated, but few have been replicated across multiple studies. METHODS: We here tested 7 candidate gene polymorphisms for association with HAD in a case-control study consisting of 86 HAD cases and 246 non-HAD AIDS patients as controls. Since infected monocytes and macrophages are thought to play an important role in the infection of the brain, 5 recently identified single nucleotide polymorphisms (SNPs affecting HIV-1 replication in macrophages in vitro were also tested. RESULTS: The CCR5 wt/Δ32 genotype was only associated with HAD in individuals who developed AIDS prior to 1991, in agreement with the observed fading effect of this genotype on viral load set point. A significant difference in genotype distribution among all cases and controls irrespective of year of AIDS diagnosis was found only for a SNP in candidate gene PREP1 (p = 1.2 × 10(-5. Prep1 has recently been identified as a transcription factor preferentially binding the -2,518 G allele in the promoter of the gene encoding MCP-1, a protein with a well established role in the etiology of HAD. CONCLUSION: These results support previous findings suggesting an important role for MCP-1 in the onset of HIV-1-associated neurocognitive disorders.

Psychiatric disorders, HIV infection and HIV/hepatitis co-infection in the correctional setting.

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Baillargeon, J G; Paar, D P; Wu, H; Giordano, T P; Murray, O; Raimer, B G; Avery, E N; Diamond, P M; Pulvino, J S

2008-01-01

Psychiatric disorders such as bipolar disorder, schizophrenia and depression have long been associated with risk behaviors for HIV, hepatitis C virus (HCV) and hepatitis B virus (HBV). The US prison population is reported to have elevated rates of HIV, hepatitis and most psychiatric disorders. This study examined the association of six major psychiatric disorders with HIV mono-infection, HIV/HCV co-infection and HIV/HBV co-infection in one of the nation's largest prison populations. The study population consisted of 370,511 Texas Department of Criminal Justice inmates who were incarcerated for any duration between January 1, 2003 and July 1, 2006. Information on medical conditions and sociodemographic factors was obtained from an institution-wide electronic medical information system. Offenders diagnosed with HIV mono-infection, HIV/HCV, HIV/HBV and all HIV combined exhibited elevated rates of major depression, bipolar disorder, schizophrenia, schizoaffective disorder, non-schizophrenic psychotic disorder and any psychiatric disorder. In comparison to offenders with HIV mono-infection, those with HIV/HCV co-infection had an elevated prevalence of any psychiatric disorder. This cross-sectional study's finding of positive associations between psychiatric disease and both HIV infection and hepatitis co-infection among Texas prison inmates holds both clinical and public health relevance. It will be important for future investigations to examine the extent to which psychiatric disorders serve as a barrier to medical care, communication with clinicians and adherence to prescribed medical regimens among both HIV-mono-infected and HIV/hepatitis-co-infected inmates.

Cardio-Thoracic Ratio Is Stable, Reproducible and Has Potential as a Screening Tool for HIV-1 Related Cardiac Disorders in Resource Poor Settings.

Directory of Open Access Journals (Sweden)

Hanif Esmail

Full Text Available Cardiovascular disorders are common in HIV-1 infected persons in Africa and presentation is often insidious. Development of screening algorithms for cardiovascular disorders appropriate to a resource-constrained setting could facilitate timely referral. Cardiothoracic ratio (CTR on chest radiograph (CXR has been suggested as a potential screening tool but little is known about its reproducibility and stability. Our primary aim was to evaluate the stability and the inter-observer variability of CTR in HIV-1 infected outpatients. We further evaluated the prevalence of cardiomegaly (CTR≥0.5 and its relationship with other risk factors in this population.HIV-1 infected participants were identified during screening for a tuberculosis vaccine trial in Khayelitsha, South Africa between August 2011 and April 2012. Participants had a digital posterior-anterior CXR performed as well as history, examination and baseline observations. CXRs were viewed using OsiriX software and CTR calculated using digital callipers.450 HIV-1-infected adults were evaluated, median age 34 years (IQR 30-40 with a CD4 count 566/mm3 (IQR 443-724, 70% on antiretroviral therapy (ART. The prevalence of cardiomegaly was 12.7% (95% C.I. 9.6%-15.8%. CTR was calculated by a 2nd reader for 113 participants, measurements were highly correlated r = 0.95 (95% C.I. 0.93-0.97 and agreement of cardiomegaly substantial κ = 0.78 (95% C.I 0.61-0.95. CXR were repeated in 51 participants at 4-12 weeks, CTR measurements between the 2 time points were highly correlated r = 0.77 (95% C.I 0.68-0.88 and agreement of cardiomegaly excellent κ = 0.92 (95% C.I. 0.77-1. Participants with cardiomegaly had a higher median BMI (31.3; IQR 27.4-37.4 versus 26.9; IQR 23.2-32.4; p<0.0001 and median systolic blood pressure (130; IQR 121-141 versus 125; IQR 117-135; p = 0.01.CTR is a robust measurement, stable over time with substantial inter-observer agreement. A prospective study evaluating utility of CXR to

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

An empirical test of the information-motivation-behavioral skills model of ART adherence in a sample of HIV-positive persons primarily in out-of-HIV-care settings.

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Horvath, Keith J; Smolenski, Derek; Amico, K Rivet

2014-02-01

The current body of evidence supporting the Information-Motivation-Behavioral Skills (IMB) model of antiretroviral therapy (ART) adherence rests exclusively on data collected from people living with HIV (PLWH) at point-of-HIV-care services. The aims of this study were to: (1) determine if the IMB model is a useful predictive model of ART adherence among PLWH who were primarily recruited in out-of-HIV-care settings; and (2) assess whether the theorized associations between IMB model constructs and adherence persist in the presence of depression and current drug use. PLWH (n = 312) responding to a one-time online survey completed the Life Windows IMB-ART-Adherence Questionnaire, and demographic, depression (CES-D 10), and drug use items. Path models were used to assess the fit of a saturated versus fully mediated IMB model of adherence and examined for moderating effects of depression and current drug use. Participants were on average 43 years of age, had been living with HIV for 9 or more years, and mostly male (84.0%), Caucasian (68.8%), and gay-identified (74.8%). The a priori measurement models for information and behavioral skills did not have acceptable fit to the data and were modified accordingly. Using the revised IMB scales, IMB constructs were associated with adherence as predicted by the theory in all but one model (i.e., the IMB model operated as predicted among nondrug users and those with and without depression). Among drug users, information exerted a direct effect on adherence but was not significantly associated with behavioral skills. Results of this study suggest that the fully or partially mediated IMB model is supported for use with samples of PLWH recruited primarily out-of-HIV-care service settings and is robust in the presence of depression and drug use.

Improving outcomes in infants of HIV-infected women in a developing country setting.

Science.gov (United States)

Noel, Francine; Mehta, Sapna; Zhu, Yuwei; Rouzier, Patricia De Matteis; Marcelin, Abdias; Shi, Jian R; Nolte, Claudine; Severe, Linda; Deschamps, Marie Marcelle; Fitzgerald, Daniel W; Johnson, Warren D; Wright, Peter F; Pape, Jean W

2008-01-01

Since 1999 GHESKIO, a large voluntary counseling and HIV testing center in Port-au-Prince, Haiti, has had an ongoing collaboration with the Haitian Ministry of Health to reduce the rate of mother to child HIV transmission. There are limited data on the ability to administer complex regimens for reducing mother to child transmission and on risk factors for continued transmission and infant mortality within programmatic settings in developing countries. We analyzed data from 551 infants born to HIV-infected mothers seen at GHESKIO, between 1999 and 2005. HIV-infected mothers and their infants were given "short-course" monotherapy with antiretrovirals for prophylaxis; and, since 2003, highly active antiretroviral therapy (HAART) when clinical or laboratory indications were met. Infected women seen in the pre-treatment era had 27% transmission rates, falling to 10% in this cohort of 551 infants, and to only 1.9% in infants of women on HAART. Mortality rate after HAART introduction (0.12 per year of follow-up [0.08-0.16]) was significantly lower than the period before the availability of such therapy (0.23 [0.16-0.30], Pbirth weight on mortality and transmission were determined using univariate and multivariate analysis. Infant HIV-1 infection and low birth weight were associated with infant mortality in less than 15 month olds in multivariate analysis. Our findings demonstrate success in prevention of mother-to-child HIV transmission and mortality in a highly resource constrained setting. Elements contributing to programmatic success include provision of HAART in the context of a comprehensive program with pre and postnatal care for both mother and infant.

Evaluation of Calypte AWARE HIV-1/2 OMT antibody test as a screening test in an Indian setting

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Ingole N

2010-01-01

Full Text Available Purpose: Integrated counselling and testing centres (ICTC provide counselling and blood testing facilities for HIV diagnosis. Oral fluid tests provide an alternative for people whodo not want blood to be drawn. Also, it avoids the risk of occupational exposure. The goal of this study was to evaluate the utility of Calypte AWARE HIV-1/2 OMT antibody test as a screening test in an Indian setting. Materials and Methods: A cross-sectional study was carried out after ethics committee approval in 250 adult ICTC clients. Blood was collected and tested from these clients for HIV diagnosis as per routine policy and the results were considered as the gold standard. Also, after another written informed consent, oral fluid was collected from the clients and tested for the presence of HIV antibodies. Twenty five clients who had and 25 clients who had not completed their secondary school education (Group A and Group B, respectively were also asked to perform and interpret the test on their own and their findings and experiences were noted. Result: The sensitivity, specificity, PPV and NPV of the oral fluid antibody test were 100%, 98.51%, 94.11% and 100%, respectively. Seventy six percent of clients preferred oral fluid testing. Group B found it difficult to perform the test as compared to Group A and this difference was statistically significant (P ≤ 0.05. Conclusion: Oral fluid testing can be used as a screening test for HIV diagnosis; however, confirmation of reactive results by blood-based tests is a must.

Is the virulence of HIV changing? A meta-analysis of trends in prognostic markers of HIV disease progression and transmission

Science.gov (United States)

Herbeck, Joshua T.; Müller, Viktor; Maust, Brandon S.; Ledergerber, Bruno; Torti, Carlo; Di Giambenedetto, Simona; Gras, Luuk; Günthard, Huldrych F.; Jacobson, Lisa P.; Mullins, James I.; Gottlieb, Geoffrey S.

2013-01-01

Objective The potential for changing HIV-1 virulence has significant implications for the AIDS epidemic, including changing HIV transmission rates, rapidity of disease progression, and timing of ART. Published data to date have provided conflicting results. Design We conducted a meta-analysis of changes in baseline CD4+ T-cell counts and set point plasma viral RNA load over time in order to establish whether summary trends are consistent with changing HIV-1 virulence. Methods We searched PubMed for studies of trends in HIV-1 prognostic markers of disease progression and supplemented findings with publications referenced in epidemiological or virulence studies. We identified 12 studies of trends in baseline CD4+ T-cell counts (21 052 total individuals), and eight studies of trends in set point viral loads (10 785 total individuals), spanning the years 1984–2010. Using random-effects meta-analysis, we estimated summary effect sizes for trends in HIV-1 plasma viral loads and CD4+ T-cell counts. Results Baseline CD4+ T-cell counts showed a summary trend of decreasing cell counts [effect=−4.93 cells/µl per year, 95% confidence interval (CI) −6.53 to −3.3]. Set point viral loads showed a summary trend of increasing plasma viral RNA loads (effect=0.013 log10 copies/ml per year, 95% CI −0.001 to 0.03). The trend rates decelerated in recent years for both prognostic markers. Conclusion Our results are consistent with increased virulence of HIV-1 over the course of the epidemic. Extrapolating over the 30 years since the first description of AIDS, this represents a CD4+ T cells loss of approximately 148 cells/µl and a gain of 0.39 log10 copies/ml of viral RNA measured during early infection. These effect sizes would predict increasing rates of disease progression, and need for ART as well as increasing transmission risk. PMID:22089381

The Depsipeptide Romidepsin Reverses HIV-1 Latency In Vivo.

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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.

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.

Performance of the Xpert HIV-1 Viral Load Assay: a Systematic Review and Meta-analysis.

Science.gov (United States)

Nash, Madlen; Huddart, Sophie; Badar, Sayema; Baliga, Shrikala; Saravu, Kavitha; Pai, Madhukar

2018-04-01

Viral load (VL) is the preferred treatment-monitoring approach for HIV-positive patients. However, more rapid, near-patient, and low-complexity assays are needed to scale up VL testing. The Xpert HIV-1 VL assay (Cepheid, Sunnyvale, CA) is a new, automated molecular test, and it can leverage the GeneXpert systems that are being used widely for tuberculosis diagnosis. We systematically reviewed the evidence on the performance of this new tool in comparison to established reference standards. A total of 12 articles (13 studies) in which HIV patient VLs were compared between Xpert HIV VL assay and a reference standard VL assay were identified. Study quality was generally high, but substantial variability was observed in the number and type of agreement measures reported. Correlation coefficients between Xpert and reference assays were high, with a pooled Pearson correlation ( n = 8) of 0.94 (95% confidence interval [CI], 0.89, 0.97) and Spearman correlation ( n = 3) of 0.96 (95% CI, 0.86, 0.99). Bland-Altman metrics ( n = 11) all were within 0.35 log copies/ml of perfect agreement. Overall, Xpert HIV-1 VL performed well compared to current reference tests. The minimal training and infrastructure requirements for the Xpert HIV-1 VL assay make it attractive for use in resource-constrained settings, where point-of-care VL testing is most needed. Copyright © 2018 Nash et al.

Cellular Antiviral Factors that Target Particle Infectivity of HIV-1.

Science.gov (United States)

Goffinet, Christine

2016-01-01

In the past decade, the identification and characterization of antiviral genes with the ability to interfere with virus replication has established cell-intrinsic innate immunity as a third line of antiviral defense in addition to adaptive and classical innate immunity. Understanding how cellular factors have evolved to inhibit HIV-1 reveals particularly vulnerable points of the viral replication cycle. Many, but not all, antiviral proteins share type I interferon-upregulated expression and sensitivity to viral counteraction or evasion measures. Whereas well-established restriction factors interfere with early post-entry steps and release of HIV-1, recent research has revealed a diverse set of proteins that reduce the infectious quality of released particles using individual, to date poorly understood modes of action. These include induction of paucity of mature glycoproteins in nascent virions or self-incorporation into the virus particle, resulting in poor infectiousness of the virion and impaired spread of the infection. A better understanding of these newly discovered antiviral factors may open new avenues towards the design of drugs that repress the spread of viruses whose genomes have already integrated.

Power Trip Set-points of Reactor Protection System for New Research Reactor

International Nuclear Information System (INIS)

Lee, Byeonghee; Yang, Soohyung

2013-01-01

This paper deals with the trip set-point related to the reactor power considering the reactivity induced accident (RIA) of new research reactor. The possible scenarios of reactivity induced accidents were simulated and the effects of trip set-point on the critical heat flux ratio (CHFR) were calculated. The proper trip set-points which meet the acceptance criterion and guarantee sufficient margins from normal operation were then determined. The three different trip set-points related to the reactor power are determined based on the RIA of new research reactor during FP condition, over 0.1%FP and under 0.1%FP. Under various reactivity insertion rates, the CHFR are calculated and checked whether they meet the acceptance criterion. For RIA at FP condition, the acceptance criterion can be satisfied even if high power set-point is only used for reactor trip. Since the design of the reactor is still progressing and need a safety margin for possible design changes, 18 MW is recommended as a high power set-point. For RIA at 0.1%FP, high power setpoint of 18 MW and high log rate of 10%pp/s works well and acceptance criterion is satisfied. For under 0.1% FP operations, the application of high log rate is necessary for satisfying the acceptance criterion. Considering possible decrease of CHFR margin due to design changes, the high log rate is suggested to be 8%pp/s. Suggested trip set-points have been identified based on preliminary design data for new research reactor; therefore, these trip set-points will be re-established by considering design progress of the reactor. The reactor protection system (RPS) of new research reactor is designed for safe shutdown of the reactor and preventing the release of radioactive material to environment. The trip set point of RPS is essential for reactor safety, therefore should be determined to mitigate the consequences from accidents. At the same time, the trip set-point should secure margins from normal operational condition to avoid

The introduction of syphilis point of care tests in resource limited settings.

Science.gov (United States)

Marks, Michael; Mabey, David Cw

2017-04-01

Syphilis remains an important and preventable cause of stillbirth and neonatal mortality. About 1 million women with active syphilis become pregnant each year. Without treatment, 25% of them will deliver a stillborn baby and 33% a low birth weight baby with an increased chance of dying in the first month of life. Adverse pregnancy outcomes due to syphilis can be prevented by screening pregnant women, and treating those who test positive with a single dose of penicillin before 28 weeks' gestation. Areas covered: This manuscript covers the impact of syphilis on pregnancy outcome, the diagnosis of syphilis, with a special focus on point of care (POC) tests, and challenges to the introduction of POC tests, and their potential impact on the control and prevention of syphilis in resource limited settings. Expert commentary: POC tests for syphilis are available which meet the ASSURED criteria, and could make syphilis screening accessible to all women anywhere in the world who attend an antenatal clinic. High quality dual POC tests for HIV and syphilis could ensure that well-funded programmes for the prevention of mother to child transmission of HIV can contribute towards increased coverage of antenatal syphilis screening, and prevent more than 300,000 adverse pregnancy outcomes due to syphilis annually. Alongside investment to increase availability of syphilis POC tests, operational research is needed to understand how best to improve screening of pregnant women and to translate test availability into improved pregnancy outcomes.

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

Improving outcomes in infants of HIV-infected women in a developing country setting.

Directory of Open Access Journals (Sweden)

Francine Noel

Full Text Available Since 1999 GHESKIO, a large voluntary counseling and HIV testing center in Port-au-Prince, Haiti, has had an ongoing collaboration with the Haitian Ministry of Health to reduce the rate of mother to child HIV transmission. There are limited data on the ability to administer complex regimens for reducing mother to child transmission and on risk factors for continued transmission and infant mortality within programmatic settings in developing countries.We analyzed data from 551 infants born to HIV-infected mothers seen at GHESKIO, between 1999 and 2005. HIV-infected mothers and their infants were given "short-course" monotherapy with antiretrovirals for prophylaxis; and, since 2003, highly active antiretroviral therapy (HAART when clinical or laboratory indications were met. Infected women seen in the pre-treatment era had 27% transmission rates, falling to 10% in this cohort of 551 infants, and to only 1.9% in infants of women on HAART. Mortality rate after HAART introduction (0.12 per year of follow-up [0.08-0.16] was significantly lower than the period before the availability of such therapy (0.23 [0.16-0.30], P<0.0001. The effects of maternal health, infant feeding, completeness of prophylaxis, and birth weight on mortality and transmission were determined using univariate and multivariate analysis. Infant HIV-1 infection and low birth weight were associated with infant mortality in less than 15 month olds in multivariate analysis.Our findings demonstrate success in prevention of mother-to-child HIV transmission and mortality in a highly resource constrained setting. Elements contributing to programmatic success include provision of HAART in the context of a comprehensive program with pre and postnatal care for both mother and infant.

Disclosure of HIV status and its impact on the loss in the follow-up of HIV-infected patients on potent anti-retroviral therapy programs in a (post- conflict setting: A retrospective cohort study from Goma, Democratic Republic of Congo.

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Pierre Zalagile Akilimali

Full Text Available The study aimed to identify the impact of non-disclosure of HIV status on the loss to follow-up (LTFU of patients receiving anti-retroviral therapy.A historic cohort of HIV patients from 2 major hospitals in Goma, Democratic Republic of Congo was followed from 2004 to 2012. LTFU was defined as not taking an ART refill for a period of 3 months or longer since the last attendance, and had not yet been classified as 'dead' or 'transferred-out'. Kaplan-Meier plots were used to determine the probability of LTFU as a function of time as inclusive of the cohort. The log-rank test was used to compare survival curves based on determinants. Cox proportional hazard modeling was used to measure predictors of LTFU from the time of treatment induction until December 15th, 2012 (the end-point.The median follow-up time was 3.99 years (IQR = 2.33 to 5.59. Seventy percent of patients had shared their HIV status with others (95% CI: 66.3-73.1. The proportion of LTFU was 12% (95%CI: 9.6-14.4. Patients who did not share their HIV status (Adjusted HR 2.28, 95% CI 1.46-2.29, patients who did not live in the city of Goma (Adjusted HR 1.97, 95% CI 1.02-3.77, and those who attained secondary or higher education level (Adjusted HR 1.60, 95% CI 1.02-2.53 had a higher hazard of being LTFU.This study shows the relationship between the non-disclosure HIV status and LTFU. Healthcare workers in similar settings should pay more attention to clients who have not disclosed their HIV status, and to those living far from health settings where they receive medication.

Assessment of satisfaction with pharmaceutical services in patients receiving antiretroviral therapy in outpatient HIV treatment setting.

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Agu, Kenneth Anene; Oqua, Dorothy; Agada, Peter; Ohiaeri, Samuel I; Adesina, Afusat; Abdulkareem, Mohammed Habeeb; King, Rosalyn C; Wutoh, Anthony K

2014-06-01

The patient's perception and satisfaction are increasingly considered as a useful factor in the assessment of competency of health care providers and quality of care. However, these patient focused assessments are largely ignored when assessing health care outcomes. The study assessed the perception and satisfaction of patients receiving antiretroviral therapy (ART) with pharmaceutical services received in outpatient HIV treatment settings. Seventeen HIV treatment centres in Nigeria. This cross-sectional survey included 2,700 patients randomly selected from 26,319 HIV patients on ART, who received pharmaceutical services in the study setting. A study-specific Likert-type instrument was administered to the participants at point of exit from the pharmacy. Midpoint of the 5-point scale was computed and scores above it were regarded as positive while below as negative. Chi-square was used for inferential statistics. All reported p values were 2-sided at 95 % confidence interval (CI). Patient satisfaction with pharmaceutical services. Of 2,700 patients sampled, data from 1,617 (59.9 %) were valid for analysis; 62.3 % were aged 26-40 years and 65.4 % were females. The participants had received pharmaceutical services for a mean duration of 25.2 (95 % CI 24.3-26.1) months. Perception of participants regarding the appearance of pharmacy was positive while that regarding the pharmacists' efforts to solve patients' medication related problems was negative. The participants' rating of satisfaction with the waiting time to access pharmaceutical services was negative; the satisfaction decreases with increasing waiting time. However, the satisfaction with the overall quality of pharmaceutical services received was rated as positive; 90.0 % reported that they got the kind of pharmaceutical services they wanted; 98.2 % would come back to the pharmacy if they were to seek help again and would recommend services to others. The level of satisfaction was found to be associated with

The clinical and economic impact of point-of-care CD4 testing in mozambique and other resource-limited settings: a cost-effectiveness analysis.

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Emily P Hyle

2014-09-01

Full Text Available Point-of-care CD4 tests at HIV diagnosis could improve linkage to care in resource-limited settings. Our objective is to evaluate the clinical and economic impact of point-of-care CD4 tests compared to laboratory-based tests in Mozambique.We use a validated model of HIV testing, linkage, and treatment (CEPAC-International to examine two strategies of immunological staging in Mozambique: (1 laboratory-based CD4 testing (LAB-CD4 and (2 point-of-care CD4 testing (POC-CD4. Model outcomes include 5-y survival, life expectancy, lifetime costs, and incremental cost-effectiveness ratios (ICERs. Input parameters include linkage to care (LAB-CD4, 34%; POC-CD4, 61%, probability of correctly detecting antiretroviral therapy (ART eligibility (sensitivity: LAB-CD4, 100%; POC-CD4, 90% or ART ineligibility (specificity: LAB-CD4, 100%; POC-CD4, 85%, and test cost (LAB-CD4, US$10; POC-CD4, US$24. In sensitivity analyses, we vary POC-CD4-specific parameters, as well as cohort and setting parameters to reflect a range of scenarios in sub-Saharan Africa. We consider ICERs less than three times the per capita gross domestic product in Mozambique (US$570 to be cost-effective, and ICERs less than one times the per capita gross domestic product in Mozambique to be very cost-effective. Projected 5-y survival in HIV-infected persons with LAB-CD4 is 60.9% (95% CI, 60.9%-61.0%, increasing to 65.0% (95% CI, 64.9%-65.1% with POC-CD4. Discounted life expectancy and per person lifetime costs with LAB-CD4 are 9.6 y (95% CI, 9.6-9.6 y and US$2,440 (95% CI, US$2,440-US$2,450 and increase with POC-CD4 to 10.3 y (95% CI, 10.3-10.3 y and US$2,800 (95% CI, US$2,790-US$2,800; the ICER of POC-CD4 compared to LAB-CD4 is US$500/year of life saved (YLS (95% CI, US$480-US$520/YLS. POC-CD4 improves clinical outcomes and remains near the very cost-effective threshold in sensitivity analyses, even if point-of-care CD4 tests have lower sensitivity/specificity and higher cost than published

Striking HIV-1 Entry by Targeting HIV-1 gp41. But, Where Should We Target?

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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.

Evaluation of a manual DNA extraction protocol and an isothermal amplification assay for detecting HIV-1 DNA from dried blood spots for use in resource-limited settings.

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Jordan, Jeanne A; Ibe, Christine O; Moore, Miranda S; Host, Christel; Simon, Gary L

2012-05-01

In resource-limited settings (RLS) dried blood spots (DBS) are collected on infants and transported through provincial laboratories to a central facility where HIV-1 DNA PCR testing is performed using specialized equipment. Implementing a simpler approach not requiring such equipment or skilled personnel could allow the more numerous provincial laboratories to offer testing, improving turn-around-time to identify and treat infected infants sooner. Assess performances of a manual DNA extraction method and helicase-dependent amplification (HDA) assay for detecting HIV-1 DNA from DBS. 60 HIV-1 infected adults were enrolled, blood samples taken and DBS made. DBS extracts were assessed for DNA concentration and beta globin amplification using PCR and melt-curve analysis. These same extracts were then tested for HIV-1 DNA using HDA and compared to results generated by PCR and pyrosequencing. Finally, HDA limit of detection (LOD) studies were performed using DBS extracts prepared with known numbers of 8E5 cells. The manual extraction protocol consistently yielded high concentrations of amplifiable DNA from DBS. LOD assessment demonstrated HDA detected ∼470 copies/ml of HIV-1 DNA extracts in 4/4 replicates. No statistical difference was found using the McNemar's test when comparing HDA to PCR for detecting HIV-1 DNA from DBS. Using just a magnet, heat block and pipettes, the manual extraction protocol and HDA assay detected HIV-1 DNA from DBS at levels that would be useful for early infant diagnosis. Next steps will include assessing HDA for non-B HIV-1 subtypes recognition and comparison to Roche HIV-1 DNA v1.5 PCR assay. Copyright © 2012 Elsevier B.V. All rights reserved.

Expanding HIV testing efforts in concentrated epidemic settings: a population-based survey from rural Vietnam.

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Anastasia Pharris

Full Text Available BACKGROUND: To improve HIV prevention and care programs, it is important to understand the uptake of HIV testing and to identify population segments in need of increased HIV testing. This is particularly crucial in countries with concentrated HIV epidemics, where HIV prevalence continues to rise in the general population. This study analyzes determinants of HIV testing in a rural Vietnamese population in order to identify potential access barriers and areas for promoting HIV testing services. METHODS: A population-based cross-sectional survey of 1874 randomly sampled adults was linked to pregnancy, migration and economic cohort data from a demographic surveillance site (DSS. Multivariate logistic regression analysis was used to determine which factors were associated with having tested for HIV. RESULTS: The age-adjusted prevalence of ever-testing for HIV was 7.6%; however 79% of those who reported feeling at-risk of contracting HIV had never tested. In multivariate analysis, younger age (aOR 1.85, 95% CI 1.14-3.01, higher economic status (aOR 3.4, 95% CI 2.21-5.22, and semi-urban residence (aOR 2.37, 95% CI 1.53-3.66 were associated with having been tested for HIV. HIV testing rates did not differ between women of reproductive age who had recently been pregnant and those who had not. CONCLUSIONS: We found low testing uptake (6% among pregnant women despite an existing prevention of mother-to-child HIV testing policy, and lower-than-expected testing among persons who felt that they were at-risk of HIV. Poverty and residence in a more geographically remote location were associated with less HIV testing. In addition to current HIV testing strategies focusing on high-risk groups, we recommend targeting HIV testing in concentrated HIV epidemic settings to focus on a scaled-up provision of antenatal testing. Additional recommendations include removing financial and geographic access barriers to client-initiated testing, and encouraging provider

Expanding HIV testing efforts in concentrated epidemic settings: a population-based survey from rural Vietnam.

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Pharris, Anastasia; Nguyen, Thi Kim Chuc; Tishelman, Carol; Brugha, Ruairí; Nguyen, Phuong Hoa; Thorson, Anna

2011-01-11

To improve HIV prevention and care programs, it is important to understand the uptake of HIV testing and to identify population segments in need of increased HIV testing. This is particularly crucial in countries with concentrated HIV epidemics, where HIV prevalence continues to rise in the general population. This study analyzes determinants of HIV testing in a rural Vietnamese population in order to identify potential access barriers and areas for promoting HIV testing services. A population-based cross-sectional survey of 1874 randomly sampled adults was linked to pregnancy, migration and economic cohort data from a demographic surveillance site (DSS). Multivariate logistic regression analysis was used to determine which factors were associated with having tested for HIV. The age-adjusted prevalence of ever-testing for HIV was 7.6%; however 79% of those who reported feeling at-risk of contracting HIV had never tested. In multivariate analysis, younger age (aOR 1.85, 95% CI 1.14-3.01), higher economic status (aOR 3.4, 95% CI 2.21-5.22), and semi-urban residence (aOR 2.37, 95% CI 1.53-3.66) were associated with having been tested for HIV. HIV testing rates did not differ between women of reproductive age who had recently been pregnant and those who had not. We found low testing uptake (6%) among pregnant women despite an existing prevention of mother-to-child HIV testing policy, and lower-than-expected testing among persons who felt that they were at-risk of HIV. Poverty and residence in a more geographically remote location were associated with less HIV testing. In addition to current HIV testing strategies focusing on high-risk groups, we recommend targeting HIV testing in concentrated HIV epidemic settings to focus on a scaled-up provision of antenatal testing. Additional recommendations include removing financial and geographic access barriers to client-initiated testing, and encouraging provider-initiated testing of those who believe that they are at-risk of

Assessing the effect of an online HIV/AIDS course on 1st-year ...

African Journals Online (AJOL)

Background. More international HIV/AIDS intervention initiatives targeting young adults are needed to help reach targets set by the Joint United Nations Programme on HIV and AIDS (UNAIDS). Objectives. To determine the effect of an online HIV/AIDS course on 1st-year pharmacy students' knowledge of HIV prevention and ...

Association between Perceived Discrimination in Healthcare Settings and HIV Medication Adherence: Mediating Psychosocial Mechanisms.

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Turan, Bulent; Rogers, Anna Joy; Rice, Whitney S; Atkins, Ghislaine C; Cohen, Mardge H; Wilson, Tracey E; Adimora, Adaora A; Merenstein, Daniel; Adedimeji, Adebola; Wentz, Eryka L; Ofotokun, Igho; Metsch, Lisa; Tien, Phyllis C; Johnson, Mallory O; Turan, Janet M; Weiser, Sheri D

2017-12-01

There is insufficient research on the impact of perceived discrimination in healthcare settings on adherence to antiretroviral therapy (ART), particularly among women living with HIV, and even less is known about psychosocial mechanisms that may mediate this association. Cross-sectional analyses were conducted in a sample of 1356 diverse women living with HIV enrolled in the Women's Interagency HIV Study (WIHS), a multi-center cohort study. Indirect effects analysis with bootstrapping was used to examine the potential mediating roles of internalized stigma and depressive symptoms in the association between perceived discrimination in healthcare settings and ART adherence. Perceived discrimination in healthcare settings was negatively associated with optimal (95% or better) ART adherence (adjusted odds ratio (AOR) = 0.81, p = 0.02, 95% confidence interval (CI) [0.68, 0.97]). Furthermore, internalization of stigma and depressive symptoms mediated the perceived discrimination-adherence association: Serial mediation analyses revealed a significant indirect effect of perceived discrimination in healthcare settings on ART adherence, first through internalized HIV stigma, and then through depressive symptoms (B = - 0.08, SE = 0.02, 95% CI [- 0.12, - 0.04]). Perceiving discrimination in healthcare settings may contribute to internalization of HIV-related stigma, which in turn may lead to depressive symptoms, with downstream adverse effects on ART adherence among women. These findings can guide the design of interventions to reduce discrimination in healthcare settings, as well as interventions targeting psychosocial mechanisms that may impact the ability of women living with HIV to adhere to ART regimens.

Association between HIV-1 coreceptor usage and resistance to broadly neutralizing antibodies.

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Pfeifer, Nico; Walter, Hauke; Lengauer, Thomas

2014-10-01

Recently discovered broadly neutralizing antibodies have revitalized hopes of developing a universal vaccine against HIV-1. Mainly responsible for new infections are variants only using CCR5 for cell entry, whereas CXCR4-using variants can become dominant in later infection stages. We performed a statistical analysis on two different previously published data sets. The first data set was a panel of 199 diverse HIV-1 isolates for which IC50 neutralization titers were determined for the broadly neutralizing antibodies VRC01, VRC-PG04, PG9, and PG16. The second data set contained env sequences of viral variants extracted from HIV-1-infected humanized mice treated with the antibody PGT128 and from untreated control mice. For the panel of 199 diverse HIV-1 isolates, we found a statistically significant association between viral resistance to PG9 and PG16 and CXCR4 coreceptor usage (P = 0.0011 and P = 0.0010, respectively). Our analysis of viral variants from HIV-1-infected humanized mice under treatment with the broadly neutralizing antibody PGT128 indicated that certain antibodies might drive a viral population toward developing CXCR4 coreceptor usage capability (P = 0.0011 for the comparison between PGT128 and control measurement). These analyses highlight the importance of accounting for a possible coreceptor usage bias pertaining to the effectiveness of an HIV vaccine and to passive antibody transfer as therapeutic approach.

Uptake of Community-Based Peer Administered HIV Point-of-Care Testing: Findings from the PROUD Study.

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Lisa Lazarus

Full Text Available HIV prevalence among people who inject drugs (PWID in Ottawa is estimated at about 10%. The successful integration of peers into outreach efforts and wider access to HIV point-of-care testing (POCT create opportunities to explore the role of peers in providing HIV testing. The PROUD study, in partnership with Ottawa Public Health (OPH, sought to develop a model for community-based peer-administered HIV POCT.PROUD draws on community-based participatory research methods to better understand the HIV risk environment of people who use drugs in Ottawa. From March-October 2013, 593 people who reported injecting drugs or smoking crack cocaine were enrolled through street-based recruitment. Trained peer or medical student researchers administered a quantitative survey and offered an HIV POCT (bioLytical INSTI test to participants who did not self-report as HIV positive.550 (92.7% of the 593 participants were offered a POCT, of which 458 (83.3% consented to testing. Of those participants, 74 (16.2% had never been tested for HIV. There was no difference in uptake between testing offered by a peer versus a non-peer interviewer (OR = 1.05; 95% CI = 0.67-1.66. Despite testing those at high risk for HIV, only one new reactive test was identified.The findings from PROUD demonstrate high uptake of community-based HIV POCT. Peers were able to successfully provide HIV POCT and reach participants who had not previously been tested for HIV. Community-based and peer testing models provide important insights on ways to scale-up HIV prevention and testing among people who use drugs.

The latest evidence for possible HIV-1 curative strategies.

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Pham, Hanh Thi; Mesplède, Thibault

2018-01-01

Human immunodeficiency virus type 1 (HIV-1) infection remains a major health issue worldwide. In developed countries, antiretroviral therapy has extended its reach from treatment of people living with HIV-1 to post-exposure prophylaxis, treatment as prevention, and, more recently, pre-exposure prophylaxis. These healthcare strategies offer the epidemiological tools to curve the epidemic in rich settings and will be concomitantly implemented in developing countries. One of the remaining challenges is to identify an efficacious curative strategy. This review manuscript will focus on some of the current curative strategies aiming at providing a sterilizing or functional cure to HIV-1-positive individuals. These include the following: early treatment initiation in post-treatment controllers as a long-term HIV-1 remission strategy, latency reversal, gene editing with or without stem cell transplantation, and antibodies against either the viral envelope protein or the host integrin α4β7.

On the structure of the set of coincidence points

Energy Technology Data Exchange (ETDEWEB)

Arutyunov, A V [Peoples Friendship University of Russia, Moscow (Russian Federation); Gel' man, B D [Voronezh State University (Russian Federation)

2015-03-31

We consider the set of coincidence points for two maps between metric spaces. Cardinality, metric and topological properties of the coincidence set are studied. We obtain conditions which guarantee that this set (a) consists of at least two points; (b) consists of at least n points; (c) contains a countable subset; (d) is uncountable. The results are applied to study the structure of the double point set and the fixed point set for multivalued contractions. Bibliography: 12 titles.

Epidemiology, Diagnosis, and Treatment of HIV-Associated Non-Hodgkin Lymphoma in Resource-Limited Settings

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Matthew Ulrickson

2012-01-01

Full Text Available Lymphoma was a common complication of HIV infection in the pre-antiretroviral era, and the incidence of HIV-associated lymphoma has dropped dramatically since the introduction of combination antiretroviral therapy (cART in resource-rich regions. Conversely, lymphoma is an increasingly common complication of HIV infection in resource-limited settings where the prevalence of HIV infection is high. Relatively little is known, however, about the true incidence and optimal treatment regimens for HIV-associated lymphoma in resource-poor regions. We review the epidemiology, diagnosis, and treatment of HIV-associated non-Hodgkin lymphoma in developing nations and highlight areas for further research that may benefit care in both settings. Examples include risk modification and dose modification of chemotherapy based on HIV risk factors, improving our understanding of the current burden of disease through national cancer registries, and developing cost-effective hematopathological diagnostic strategies to optimize care delivery and maximize use of available chemotherapy.

The Gut Microbiome and HIV-1 Pathogenesis: A Two Way Street

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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

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

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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.

Advancing Toward HIV-1 Vaccine Efficacy through the Intersections of Immune Correlates

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Georgia D. Tomaras

2013-12-01

Full Text Available Interrogating immune correlates of infection risk for efficacious and non-efficacious HIV-1 vaccine clinical trials have provided hypotheses regarding the mechanisms of induction of protective immunity to HIV-1. To date, there have been six HIV-1 vaccine efficacy trials (VAX003, Vaxgen, Inc., San Francisco, CA, USA, VAX004 (Vaxgen, Inc., HIV-1 Vaccine Trials Network (HVTN 502 (Step, HVTN 503 (Phambili, RV144 (sponsored by the U.S. Military HIV Research Program, MHRP and HVTN 505. Cellular, humoral, host genetic and virus sieve analyses of these human clinical trials each can provide information that may point to potentially protective mechanisms for vaccine-induced immunity. Critical to staying on the path toward development of an efficacious vaccine is utilizing information from previous human and non-human primate studies in concert with new discoveries of basic HIV-1 host-virus interactions. One way that past discoveries from correlate analyses can lead to novel inventions or new pathways toward vaccine efficacy is to examine the intersections where different components of the correlate analyses overlap (e.g., virus sieve analysis combined with humoral correlates that can point to mechanistic hypotheses. Additionally, differences in durability among vaccine-induced T- and B-cell responses indicate that time post-vaccination is an important variable. Thus, understanding the nature of protective responses, the degree to which such responses have, or have not, as yet, been induced by previous vaccine trials and the design of strategies to induce durable T- and B-cell responses are critical to the development of a protective HIV-1 vaccine.

ACUTE HIV: WHAT IS NEW AND DO WE TREAT? clinical

African Journals Online (AJOL)

Acute HIV infection (AHI) is usually defined as the time from entry of the virus into the body to completion of seroconversion, while early-stage HIV infection gener- ally refers to the interval between seroconversion and the establishment of the viral load set point. The mag- nitude of the viral set point is prognostic for disease.

Low Prevalence of Transmitted HIV Type 1 Drug Resistance Among Antiretroviral-Naive Adults in a Rural HIV Clinic in Kenya

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Hassan, Amin S.; Mwaringa, Shalton M.; Obonyo, Clare A.; Nabwera, Helen M.; Sanders, Eduard J.; Rinke de Wit, Tobias F.; Cane, Patricia A.; Berkley, James A.

2013-01-01

Low levels of HIV-1 transmitted drug resistance (TDR) have previously been reported from many parts of sub-Saharan Africa (sSA). However, recent data, mostly from urban settings, suggest an increase in the prevalence of HIV-1 TDR. Our objective was to determine the prevalence of TDR mutations among

Identification and genetic characterization of unique HIV-1 A1/C recombinant strain in South Africa.

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Musyoki, Andrew M; Rakgole, Johnny N; Selabe, Gloria; Mphahlele, Jeffrey

2015-03-01

HIV isolates from South Africa are predominantly subtype C. Sporadic isolation of non-C strains has been reported mainly in cosmopolitan cities. HIV isolate j51 was recovered from a rural South African heterosexual female aged 51 years. Near full length amplification of the genome was attempted using PCR with primers targeting overlapping segments of the HIV genome. Analysis of 5593 bp (gag to vpu) at a bootstrap value greater than 70% found that all but the vpu gene was HIV-1 subtype A1. The vpu gene was assigned HIV-1 subtype C. The recombination breaking point was estimated at position 6035+/- 15 bp with reference to the beginning of the HXB2 reference strain. Isolate j51 revealed a unique genome constellation to previously reported recombinant strains with parental A/C backbones from South Africa though a common recombination with subtype C within the vpu gene. Identification of recombinant strains supports continued surveillance of HIV genetic diversity.

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.

A "Mindful Rational Living" Approach for Addressing HIV in the School Setting

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Chenneville, Tiffany; St. John Walsh, Audra

2016-01-01

This paper describes a "mindful rational living" approach, which incorporates mindfulness techniques with rational emotive behavioral therapy strategies for addressing HIV in the school setting. The utility of this approach for attending to the physical, mental, and psychosocial aspects of school-based HIV prevention and treatment will…

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.

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

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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.

Human cellular restriction factors that target HIV-1 replication

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Jeang Kuan-Teh

2009-09-01

Full Text Available Abstract Recent findings have highlighted roles played by innate cellular factors in restricting intracellular viral replication. In this review, we discuss in brief the activities of apolipoprotein B mRNA-editing enzyme 3G (APOBEC3G, bone marrow stromal cell antigen 2 (BST-2, cyclophilin A, tripartite motif protein 5 alpha (Trim5α, and cellular microRNAs as examples of host restriction factors that target HIV-1. We point to countermeasures encoded by HIV-1 for moderating the potency of these cellular restriction functions.

The Epidemic History of HIV-1 CRF07_BC in Hetian Prefecture and the Role of It on HIV Spreading in China.

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Wu, Jianjun; Guo, Hongxiong; Zhang, Jing; Liu, Xiaoming; Ayoupu, Aideaierli; Shen, Yuelan; Miao, Lifeng; Tang, Jihai; Lei, Yanhua; Su, Bin

2017-04-01

CRF07_BC is one of the most prevalent HIV-1 strains in China, and Xinjiang Uygur Autonomous Region has ever been considered to be a second epidemic center after Yunnan Province in previous studies. Here we use HIV-1 pol gene sequences identified from Hetian Prefecture located in Xinjiang Autonomous Region to reconstruct the epidemic history of HIV CRF07_BC strain circulating in this region. We found that CRF07_BC is the predominant HIV-1 form in Hetian Prefecture, and the estimated tMRCA analysis shows that there is no enough evidence supporting Xinjiang Autonomous Region as a second epidemic center of spreading HIV-1. It may imply that every city may be only a point among the HIV spreading network because of the frequent migration of population in the whole country nowadays.

Routine HIV screening in two health-care settings--New York City and New Orleans, 2011-2013.

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Lin, Xia; Dietz, Patricia M; Rodriguez, Vanessa; Lester, Deborah; Hernandez, Paloma; Moreno-Walton, Lisa; Johnson, Grant; Van Handel, Michelle M; Skarbinski, Jacek; Mattson, Christine L; Stratford, Dale; Belcher, Lisa; Branson, Bernard M

2014-06-27

Approximately 16% of the estimated 1.1 million persons living with human immunodeficiency virus (HIV) in the United States are unaware of their infection and thus unable to benefit from effective treatment that improves health and reduces transmission risk. Since 2006, CDC has recommended that health-care providers screen for HIV all patients aged 13-64 years unless prevalence of undiagnosed HIV infection in their patients has been documented to be New York City and the Interim Louisiana Hospital (ILH) in New Orleans. Data were provided by the two programs. UHP screened a monthly average of 986 patients for HIV during January 2011-September 2013. Of the 32,534 patients screened, 148 (0.45%) tested HIV-positive, of whom 147 (99%) received their test result and 43 (29%) were newly diagnosed. None of the 148 patients with HIV infection were previously receiving medical care, and 120 (81%) were linked to HIV medical care. The ILH emergency department (ED) and the urgent-care center (UCC) screened a monthly average of 1,323 patients from mid-March to December 2013. Of the 12,568 patients screened, 102 (0.81%) tested HIV-positive, of whom 100 (98%) received their test result, 77 (75%) were newly diagnosed, and five (5%) had acute HIV infection. Linkage to HIV medical care was successful for 67 (74%) of 91 patients not already in care. Routine HIV screening identified patients with new and previously diagnosed HIV infection and facilitated their linkage to medical care. The two HIV screening programs highlighted in this report can serve as models that could be adapted by other health-care settings.

Sensitivity and specificity of dried blood spots for HIV-1 viral load quantification: A laboratory assessment of 3 commercial assays.

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Pannus, Pieter; Claus, Maarten; Gonzalez, Maria Mercedes Perez; Ford, Nathan; Fransen, Katrien

2016-11-01

The use of dried blood spots (DBS) instead of plasma as a specimen type for HIV-1 viral load (VL) testing facilitates the decentralization of specimen collection and can increase access to VL testing in resource-limited settings. The performance of DBS for VL testing is lower, however, when compared to the gold standard sample type plasma. In this diagnostic accuracy study, we evaluated 3 VL assays with DBS.Participants were recruited between August 2012 and April 2015. Both plasma and DBS specimens were prepared and tested for HIV-1 VL with the Roche CAP/CTM HIV-1 test v2.0, the Abbott RealTime HIV-1, and the bioMérieux NucliSENS EasyQ HIV-1 v2.0. Sensitivity and specificity to detect treatment failure at a threshold of 1000 cps/mL with DBS were determined.A total of 272 HIV-positive patients and 51 HIV-negative people were recruited in the study. The mean difference or bias between plasma and DBS VL was 25% of the specimens differed by >0.5 log cps/mL.All 3 assays had comparable sensitivities around 80% and specificities around 90%. Upward misclassification rates were around 10%, but downward misclassification rates ranged from 20.3% to 23.6%. Differences in between assays were not statistically significant (P > 0.1).The 3 VL assays evaluated had suboptimal performance with DBS but still performed better than immunological or clinical monitoring. Even after the introduction of the much-anticipated point-of-care VL devices, it is expected that DBS will remain important as a complementary option for supporting access to VL monitoring, particularly in rural, resource-limited settings. Manufacturers should accelerate efforts to develop more reliable, sensitive and specific methods to test VL on DBS specimens.

Point of care diagnostics for HIV in resource limited settings: an overview

CSIR Research Space (South Africa)

Manoto, Sello L

2018-03-01

Full Text Available result. In the case of HIV, the analytical targets can include human cells, proteins as well as nucleic acids and the samples can be blood, saliva and urine [8]. Irrespective of where these POC tests are used, they allow a sample with little... measurement. Viral Load Tool POC Analyte Detection Method Time to Result Sample Type andVolume Additional Information SAMBA Yes RNA Isothermic amplification and Hapten-based signal detection 90 min (SI 4 sample throughput, 24–48 tests/day), (SII 4 tests a day...

HIV-1 vaccines

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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

Sequential function approximation on arbitrarily distributed point sets

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Wu, Kailiang; Xiu, Dongbin

2018-02-01

We present a randomized iterative method for approximating unknown function sequentially on arbitrary point set. The method is based on a recently developed sequential approximation (SA) method, which approximates a target function using one data point at each step and avoids matrix operations. The focus of this paper is on data sets with highly irregular distribution of the points. We present a nearest neighbor replacement (NNR) algorithm, which allows one to sample the irregular data sets in a near optimal manner. We provide mathematical justification and error estimates for the NNR algorithm. Extensive numerical examples are also presented to demonstrate that the NNR algorithm can deliver satisfactory convergence for the SA method on data sets with high irregularity in their point distributions.

Low-cost HIV-1 diagnosis and quantification in dried blood spots by real time PCR.

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Mehta, Nishaki; Trzmielina, Sonia; Nonyane, Bareng A S; Eliot, Melissa N; Lin, Rongheng; Foulkes, Andrea S; McNeal, Kristina; Ammann, Arthur; Eulalievyolo, Vindu; Sullivan, John L; Luzuriaga, Katherine; Somasundaran, Mohan

2009-06-05

Rapid and cost-effective methods for HIV-1 diagnosis and viral load monitoring would greatly enhance the clinical management of HIV-1 infected adults and children in limited-resource settings. Recent recommendations to treat perinatally infected infants within the first year of life are feasible only if early diagnosis is routinely available. Dried blood spots (DBS) on filter paper are an easy and convenient way to collect and transport blood samples. A rapid and cost effective method to diagnose and quantify HIV-1 from DBS is urgently needed to facilitate early diagnosis of HIV-1 infection and monitoring of antiretroviral therapy. We have developed a real-time LightCycler (rtLC) PCR assay to detect and quantify HIV-1 from DBS. HIV-1 RNA extracted from DBS was amplified in a one-step, single-tube system using primers specific for long-terminal repeat sequences that are conserved across all HIV-1 clades. SYBR Green dye was used to quantify PCR amplicons and HIV-1 RNA copy numbers were determined from a standard curve generated using serially diluted known copies of HIV-1 RNA. This assay detected samples across clades, has a dynamic range of 5 log(10), and %CV real-time systems demonstrated similar performance. The accuracy, reliability, genotype inclusivity and affordability, along with the small volumes of blood required for the assay suggest that the rtLC DBS assay will be useful for early diagnosis and monitoring of pediatric HIV-1 infection in resource-limited settings.

CTL epitope distribution patterns in the Gag and Nef proteins of HIV-1 from subtype A infected subjects in Kenya: Use of multiple peptide sets increases the detectable breadth of the CTL response

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Birx Deborah L

2006-04-01

Full Text Available Abstract Background Subtype A is a major strain in the HIV-1 pandemic in eastern Europe, central Asia and in certain regions of east Africa, notably in rural Kenya. While considerable effort has been focused upon mapping and defining immunodominant CTL epitopes in HIV-1 subtype B and subtype C infections, few epitope mapping studies have focused upon subtype A. Results We have used the IFN-γ ELIspot assay and overlapping peptide pools to show that the pattern of CTL recognition of the Gag and Nef proteins in subtype A infection is similar to that seen in subtypes B and C. The p17 and p24 proteins of Gag and the central conserved region of Nef were targeted by CTL from HIV-1-infected Kenyans. Several epitope/HLA associations commonly seen in subtype B and C infection were also observed in subtype A infections. Notably, an immunodominant HLA-C restricted epitope (Gag 296–304; YL9 was observed, with 8/9 HLA-CW0304 subjects responding to this epitope. Screening the cohort with peptide sets representing subtypes A, C and D (the three most prevalent HIV-1 subtypes in east Africa, revealed that peptide sets based upon an homologous subtype (either isolate or consensus only marginally improved the capacity to detect CTL responses. While the different peptide sets detected a similar number of responses (particularly in the Gag protein, each set was capable of detecting unique responses not identified with the other peptide sets. Conclusion Hence, screening with multiple peptide sets representing different sequences, and by extension different epitope variants, can increase the detectable breadth of the HIV-1-specific CTL response. Interpreting the true extent of cross-reactivity may be hampered by the use of 15-mer peptides at a single concentration and a lack of knowledge of the sequence that primed any given CTL response. Therefore, reagent choice and knowledge of the exact sequences that prime CTL responses will be important factors in

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.

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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.

First line treatment response in patients with transmitted HIV drug resistance and well defined time point of HIV infection: updated results from the German HIV-1 seroconverter study.

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Fabia Zu Knyphausen

Full Text Available BACKGROUND: Transmission of drug-resistant HIV-1 (TDR can impair the virologic response to antiretroviral combination therapy. Aim of the study was to assess the impact of TDR on treatment success of resistance test-guided first-line therapy in the German HIV-1 Seroconverter Cohort for patients infected with HIV between 1996 and 2010. An update of the prevalence of TDR and trend over time was performed. METHODS: Data of 1,667 HIV-infected individuals who seroconverted between 1996 and 2010 were analysed. The WHO drug resistance mutations list was used to identify resistance-associated HIV mutations in drug-naïve patients for epidemiological analysis. For treatment success analysis the Stanford algorithm was used to classify a subset of 323 drug-naïve genotyped patients who received a first-line cART into three resistance groups: patients without TDR, patients with TDR and fully active cART and patients with TDR and non-fully active cART. The frequency of virologic failure 5 to 12 months after treatment initiation was determined. RESULTS: Prevalence of TDR was stable at a high mean level of 11.9% (198/1,667 in the HIV-1 Seroconverter Cohort without significant trend over time. Nucleotide reverse transcriptase inhibitor resistance was predominant (6.0% and decreased significantly over time (OR = 0.92, CI = 0.87-0.98, p = 0.01. Non-nucleoside reverse transcriptase inhibitor (2.4%; OR = 1.00, CI = 0.92-1.09, p = 0.96 and protease inhibitor resistance (2.0%; OR = 0.94, CI = 0.861.03, p = 0.17 remained stable. Virologic failure was observed in 6.5% of patients with TDR receiving fully active cART, 5,6% of patients with TDR receiving non-fully active cART and 3.2% of patients without TDR. The difference between the three groups was not significant (p = 0.41. CONCLUSION: Overall prevalence of TDR remained stable at a rather high level. No significant differences in the frequency of virologic failure were

Developing strategies for HIV-1 eradication

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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

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

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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

Computer-facilitated rapid HIV testing in emergency care settings: provider and patient usability and acceptability.

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Spielberg, Freya; Kurth, Ann E; Severynen, Anneleen; Hsieh, Yu-Hsiang; Moring-Parris, Daniel; Mackenzie, Sara; Rothman, Richard

2011-06-01

Providers in emergency care settings (ECSs) often face barriers to expanded HIV testing. We undertook formative research to understand the potential utility of a computer tool, "CARE," to facilitate rapid HIV testing in ECSs. Computer tool usability and acceptability were assessed among 35 adult patients, and provider focus groups were held, in two ECSs in Washington State and Maryland. The computer tool was usable by patients of varying computer literacy. Patients appreciated the tool's privacy and lack of judgment and their ability to reflect on HIV risks and create risk reduction plans. Staff voiced concerns regarding ECS-based HIV testing generally, including resources for follow-up of newly diagnosed people. Computer-delivered HIV testing support was acceptable and usable among low-literacy populations in two ECSs. Such tools may help circumvent some practical barriers associated with routine HIV testing in busy settings though linkages to care will still be needed.

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

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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

SupT1 Cell Infusion as a Possible Cell-Based Therapy for HIV: Results from a Pilot Study in Hu-PBMC BRGS Mice

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Jonathan Fior

2016-04-01

Full Text Available In a previous in vitro study, the SupT1 cell line was explored as a decoy target for HIV-1, proposing SupT1 cell infusion as a possible cell-based therapy for HIV. In the present work, the previous in vitro model was translated into an in vivo setting. Specifically, Hu-PBMC BRGS mice were infected with a high input of HIV-1 LAI (100,000 TCID50, and 40 million 30 Gy-irradiated SupT1 cells were infused weekly for 4 weeks as a therapy. Blood samples were taken to monitor CD4+ T cell count and viral load, and mice were monitored daily for signs of illness. At the earliest time point analyzed (Week 1, there was a significantly lower plasma viral load (~10-fold in all animals treated with SupT1 cell infusion, associated with a higher CD4+ T cell count. At later time points, infection proceeded with robust viral replication and evident CD4+ T cell depletion, except in one mouse that showed complete suppression of viral replication and preservation of CD4+ T cell count. No morbidity or mortality was associated with SupT1 cell infusion. The interesting tendencies observed in the generated data suggest that this approach should be further investigated as a possible cell-based HIV therapy.

Characterization of HIV-1 antiretroviral drug resistance after second-line treatment failure in Mali, a limited-resources setting

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Maiga, Almoustapha Issiaka; Fofana, Djeneba Bocar; Cisse, Mamadou; Diallo, Fodié; Maiga, Moussa Youssoufa; Traore, Hamar Alassane; Maiga, Issouf Alassane; Sylla, Aliou; Fofana, Dionke; Taiwo, Babafemi; Murphy, Robert; Katlama, Christine; Tounkara, Anatole; Calvez, Vincent; Marcelin, Anne-Geneviève

2012-01-01

Objectives We describe the outcomes of second-line drug resistance profiles and predict the efficacy of drugs for third-line therapy in patients monitored without the benefit of plasma HIV-1 RNA viral load (VL) or resistance testing. Methods We recruited 106 HIV-1-infected patients after second-line treatment failure in Mali. VL was determined by the Abbott RealTime system and the resistance by the ViroSeq HIV-1 genotyping system. The resistance testing was interpreted using the latest version of the Stanford algorithm. Results Among the 106 patients, 93 had isolates successfully sequenced. The median age, VL and CD4 cells were respectively 35 years, 72 000 copies/mL and 146 cells/mm3. Patients were exposed to a median of 4 years of treatment and to six antiretrovirals. We found 20% of wild-type viruses. Resistance to etravirine was noted in 38%, to lopinavir in 25% and to darunavir in 12%. The duration of prior nucleos(t)ide reverse transcriptase inhibitor exposure was associated with resistance to abacavir (P < 0.0001) and tenofovir (P = 0.0001), and duration of prior protease inhibitor treatment with resistance to lopinavir (P < 0.0001) and darunavir (P = 0.06). Conclusion Long duration of therapy prior to failure was associated with high levels of resistance and is directly related to limited access to VL monitoring and delayed switches to second-line treatment, precluding efficacy of drugs for third-line therapy. This study underlines the need for governments and public health organizations to recommend the use of VL monitoring and also the availability of darunavir and raltegravir for third-line therapies in the context of limited-resource settings. PMID:22888273

HIV-1 subtype A gag variability and epitope evolution.

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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.

HIV-1 subtype A gag variability and epitope evolution.

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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.

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.

Music analysis and point-set compression

DEFF Research Database (Denmark)

Meredith, David

2015-01-01

COSIATEC, SIATECCompress and Forth’s algorithm are point-set compression algorithms developed for discovering repeated patterns in music, such as themes and motives that would be of interest to a music analyst. To investigate their effectiveness and versatility, these algorithms were evaluated...... on three analytical tasks that depend on the discovery of repeated patterns: classifying folk song melodies into tune families, discovering themes and sections in polyphonic music, and discovering subject and countersubject entries in fugues. Each algorithm computes a compressed encoding of a point......-set representation of a musical object in the form of a list of compact patterns, each pattern being given with a set of vectors indicating its occurrences. However, the algorithms adopt different strategies in their attempts to discover encodings that maximize compression.The best-performing algorithm on the folk...

HIV coreceptor phenotyping in the clinical setting.

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Low, Andrew J; Swenson, Luke C; Harrigan, P Richard

2008-01-01

The introduction of CCR5 antagonists increases the options available for constructing antiretroviral regimens. However, this option is coupled with the caveat that patients should be tested for HIV coreceptor tropism prior to initiating CCR5 antagonist-based therapy. Failure to screen for CXCR4 usage increases the risk of using an ineffective drug, thus reducing the likelihood of viral suppression and increasing their risk for developing antiretroviral resistance. This review discusses current and future methods of determining HIV tropism, with a focus on their utility in the clinical setting for screening purposes. Some of these methods include recombinant phenotypic tests, such as the Monogram Trofile assay, as well as genotype-based predictors, heteroduplex tracking assays, and flow cytometry based methods. Currently, the best evidence supports the use of phenotypic methods, although other methods of screening for HIV coreceptor usage prior to the administration of CCR5 antagonists may reduce costs and increase turnaround time over phenotypic methods. The presence of low levels of X4 virus is a challenge to all assay methods, resulting in reduced sensitivity in clinical, patient-derived samples when compared to clonally derived samples. Gaining a better understanding of the output of these assays and correlating them with clinical progression and therapy response will provide some indication on how both genotype-based, and phenotypic assays for determining HIV coreceptor usage can be improved. In addition, leveraging new technologies capable of detecting low-level minority species may provide the most significant advances in ensuring that individuals with low levels of dual/mixed tropic virus are not inadvertently prescribed CCR5 antagonists.

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.

An increase in rates of obstetric haemorrhage in a setting of high HIV seroprevalence

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E Shabalala

2017-07-01

Full Text Available Background. Obstetric haemorrhage (OH is the leading cause of maternal mortality worldwide, although, indirectly, HIV is also a leading cause of maternal mortality in some settings with a high HIV seroprevalence. Objective. To determine the possible association between increasing rates of OH and HIV or its treatment. Methods. We conducted a retrospective chart review of women with OH at King Edward VIII Hospital, Durban, South Africa, over a 3-year period (2009 - 2011, during which the drug regimen for the prevention of mother-to-child transmission was evolving from single-dose nevirapine to antenatal zidovudine combined with intrapartum nevirapine (also referred to as dual therapy, and finally to a combination or highly active antiretroviral therapy (cART or HAART. Cases of OH (including abruptio placentae, placenta praevia, unspecified antepartum haemorrhage (APH, and postpartum haemorrhage (PPH were identified from maternity delivery records, and the relevant data extracted. Results. We analysed the records of 448 women diagnosed with OH. Even though the incidence of OH was low, the study found an increasing number of cases during the 3-year period. PPH – not APH – was associated with HIV seropositivity (odds ratio 1.84, 95% confi­dence interval 1.14 - 2.95. cART was not associated with an increased risk of haemorrhage. Conclusion. HIV was associated with a high risk of PPH, and its possible association with HIV treatment needs further research.

Rapid point-of-care CD4 testing at mobile HIV testing sites to increase linkage to care: an evaluation of a pilot program in South Africa.

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Larson, Bruce A; Schnippel, Kathryn; Ndibongo, Buyiswa; Xulu, Thembisile; Brennan, Alana; Long, Lawrence; Fox, Matthew P; Rosen, Sydney

2012-10-01

A mobile HIV counseling and testing (HCT) program around Johannesburg piloted the integration of point-of-care (POC) CD4 testing, using the Pima analyzer, to improve linkages to HIV care. We report results from this pilot program for patients testing positive (n = 508) from May to October 2010. We analyzed 3 primary outcomes: assignment to testing group (offered POC CD4 or not), successful follow-up (by telephone), and completed the referral visit for HIV care within 8 weeks after HIV testing if successfully followed up. Proportions for each outcome were calculated, and relative risks were estimated using a modified Poisson approach. Three hundred eleven patients were offered the POC CD4 test, and 197 patients were not offered the test. No differences in patient characteristics were observed between the 2 groups. Approximately 62.7% of patients were successfully followed up 8 weeks after HIV testing, with no differences observed between testing groups. Among those followed up, 54.4% reported completing their referral visit. Patients offered the POC CD4 test were more likely to complete the referral visit for further HIV care (relative risk 1.25, 95% confidence interval: 1.00 to 1.57). In this mobile HCT setting, patients offered POC CD4 testing as part of the HCT services were more likely to visit a referral clinic after testing, suggesting that rapid CD4 testing technology may improve linkage to HIV care. Future research can evaluate options for adjusting HCT services if POC CD4 testing was included permanently and the cost-effectiveness of the POC CD4 testing compared with other approaches for improving linkage of care.

Provider-initiated HIV testing in health care settings: Should it ...

African Journals Online (AJOL)

centered counselling? ... SAHARA-J: Journal of Social Aspects of HIV/AIDS ... To address the resource limitations of the PITC setting, WHO and CDC suggest that patient-provider interactions during PITC may need to focus on providing information ...

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

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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.

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.

Isolation of HIV-1 from experimentally contaminated multidose local anaesthetic vials.

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Druce, J D; Locarnini, S A; Birch, C J

1995-05-15

To investigate the hypothesis that HIV can be transmitted via contamination of multidose vials of local anaesthetic solution through reuse of needles and syringes. Laboratory study. (1) By experiments with multidose vials and disposable needles and syringes, we identified a sequence of events in which HIV could contaminate the anaesthetic solution. (2) Three anaesthetic solutions were contaminated with a laboratory strain of HIV and tested by viral culture and p24 enzyme immunoassay one, two and four hours later to see how long the virus remained active. (1) Needles and syringes retained small volumes of fluid after use (mean, 25 microL; in syringe alone, mean 16 microL) which could be transferred to multidose vials of local anaesthetic. (2) 10 mL of anaesthetic solution contaminated with 8 microL of HIV-infected solution (equivalent to 1% infected lymphocytes in vivo) contained active virus one hour later. In some settings, HIV could be isolated four hours after exposure. When inadvertently contaminated with HIV, multidose solutions represent a potential source of transmissible virus.

Feasibility of Early Infant Diagnosis of HIV in Resource-Limited Settings: The ANRS 12140-PEDIACAM Study in Cameroon

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Tejiokem, Mathurin C.; Faye, Albert; Penda, Ida C.; Guemkam, Georgette; Ateba Ndongo, Francis; Chewa, Gisèle; Rekacewicz, Claire; Rousset, Dominique; Kfutwah, Anfumbom; Boisier, Pascal; Warszawski, Josiane

2011-01-01

Background Early infant diagnosis (EID) of HIV is a key-point for the implementation of early HAART, associated with lower mortality in HIV-infected infants. We evaluated the EID process of HIV according to national recommendations, in urban areas of Cameroon. Methods/Findings The ANRS12140-Pediacam study is a multisite cohort in which infants born to HIV-infected mothers were included before the 8th day of life and followed. Collection of samples for HIV DNA/RNA-PCR was planned at 6 weeks together with routine vaccination. The HIV test result was expected to be available at 10 weeks. A positive or indeterminate test result was confirmed by a second test on a different sample. Systematic HAART was offered to HIV-infected infants identified. The EID process was considered complete if infants were tested and HIV results provided to mothers/family before 7 months of age. During 2007–2009, 1587 mother-infant pairs were included in three referral hospitals; most infants (n = 1423, 89.7%) were tested for HIV, at a median age of 1.5 months (IQR, 1.4–1.6). Among them, 51 (3.6%) were HIV-infected. Overall, 1331 (83.9%) completed the process by returning for the result before 7 months (median age: 2.5 months (IQR, 2.4–3.0)). Incomplete process, that is test not performed, or result of test not provided or provided late to the family, was independently associated with late HIV diagnosis during pregnancy (adjusted odds ratio (aOR) = 1.8, 95%CI: 1.1 to 2.9, p = 0.01), absence of PMTCT prophylaxis (aOR = 2.4, 95%CI: 1.4 to 4.3, p = 0.002), and emergency caesarean section (aOR = 2.5, 95%CI: 1.5 to 4.3, p = 0.001). Conclusions In urban areas of Cameroon, HIV-infected women diagnosed sufficiently early during pregnancy opt to benefit from EID whatever their socio-economic, marital or disclosure status. Reduction of non optimal diagnosis process should focus on women with late HIV diagnosis during pregnancy especially if they did not receive any

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

Performance evaluation of the Bio-Rad Laboratories GS HIV Combo Ag/Ab EIA, a 4th generation HIV assay for the simultaneous detection of HIV p24 antigen and antibodies to HIV-1 (groups M and O) and HIV-2 in human serum or plasma.

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Bentsen, Christopher; McLaughlin, Lisa; Mitchell, Elizabeth; Ferrera, Carol; Liska, Sally; Myers, Robert; Peel, Sheila; Swenson, Paul; Gadelle, Stephane; Shriver, M Kathleen

2011-12-01

A multi-center study was conducted to evaluate the Bio-Rad GS HIV Combo Ag/Ab EIA, a 4th generation HIV-1/HIV-2 assay for the simultaneous detection of HIV p24 antigen and antibodies to HIV-1 (groups M and O) and HIV-2 in human serum or plasma in adult and pediatric populations. The objectives of the study were to assess assay performance for the detection of acute HIV infections; sensitivity in known HIV positive samples; percent agreement with HIV status; specificity in low and high risk individuals of unknown HIV status; and to compare assay performance to a 3rd generation HIV assay. The evaluation included testing 9150 samples at four U.S. clinical trial sites, using three kit lots. Unlinked samples were from routine testing, repositories or purchased from vendors. GS HIV Combo Ag/Ab EIA detection in samples from individuals in two separate populations with acute HIV infection was 95.2% (20/21) and 86.4% (38/44). Sensitivity was 100% (1603/1603) in known antibody positive [HIV-1 Groups M and O, and HIV-2] samples. HIV p24 antigen detection was 100% (53/53) in HIV-1 culture supernatants. HIV-1 seroconversion panel detection improved by a range of 0-20 days compared to a 3rd generation HIV test. Specificity was 99.9% (5989/5996) in low risk, 99.9% (959/960) in high risk and 100% (100/100) in pediatric populations. The GS HIV Combo Ag/Ab EIA significantly reduced the diagnostic window when compared to the 3rd generation screening assay, enabling earlier diagnosis of HIV infection. The performance parameters of the Bio-Rad GS HIV Combo Ag/Ab EIA are well suited for use in HIV diagnostic settings. Copyright © 2011 Elsevier B.V. All rights reserved.

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 �

Utility of the heteroduplex assay (HDA) as a simple and cost-effective tool for the identification of HIV type 1 dual infections in resource-limited settings.

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Powell, Rebecca L R; Urbanski, Mateusz M; Burda, Sherri; Nanfack, Aubin; Kinge, Thompson; Nyambi, Phillipe N

2008-01-01

The predominance of unique recombinant forms (URFs) of HIV-1 in Cameroon suggests that dual infection, the concomitant or sequential infection with genetically distinct HIV-1 strains, occurs frequently in this region; yet, identifying dual infection among large HIV cohorts in local, resource-limited settings is uncommon, since this generally relies on labor-intensive and costly sequencing methods. Consequently, there is a need to develop an effective, cost-efficient method appropriate to the developing world to identify these infections. In the present study, the heteroduplex assay (HDA) was used to verify dual or single infection status, as shown by traditional sequence analysis, for 15 longitudinally sampled study subjects from Cameroon. Heteroduplex formation, indicative of a dual infection, was identified for all five study subjects shown by sequence analysis to be dually infected. Conversely, heteroduplex formation was not detectable for all 10 HDA reactions of the singly infected study subjects. These results suggest that the HDA is a simple yet powerful and inexpensive tool for the detection of both intersubtype and intrasubtype dual infections, and that the HDA harbors significant potential for reliable, high-throughput screening for dual infection. As these infections and the recombinants they generate facilitate leaps in HIV-1 evolution, and may present major challenges for treatment and vaccine design, this assay will be critical for monitoring the continuing pandemic in regions of the world where HIV-1 viral diversity is broad.

Differential trends in the codon usage patterns in HIV-1 genes.

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Aridaman Pandit

Full Text Available Host-pathogen interactions underlie one of the most complex evolutionary phenomena resulting in continual adaptive genetic changes, where pathogens exploit the host's molecular resources for growth and survival, while hosts try to eliminate the pathogen. Deciphering the molecular basis of host-pathogen interactions is useful in understanding the factors governing pathogen evolution and disease propagation. In host-pathogen context, a balance between mutation, selection, and genetic drift is known to maintain codon bias in both organisms. Studies revealing determinants of the bias and its dynamics are central to the understanding of host-pathogen evolution. We considered the Human Immunodeficiency Virus (HIV type 1 and its human host to search for evolutionary signatures in the viral genome. Positive selection is known to dominate intra-host evolution of HIV-1, whereas high genetic variability underlies the belief that neutral processes drive inter-host differences. In this study, we analyze the codon usage patterns of HIV-1 genomes across all subtypes and clades sequenced over a period of 23 years. We show presence of unique temporal correlations in the codon bias of three HIV-1 genes illustrating differential adaptation of the HIV-1 genes towards the host preferred codons. Our results point towards gene-specific translational selection to be an important force driving the evolution of HIV-1 at the population level.

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

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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

GeneXpert HIV-1 quant assay, a new tool for scale up of viral load monitoring in the success of ART programme in India.

Science.gov (United States)

Kulkarni, Smita; Jadhav, Sushama; Khopkar, Priyanka; Sane, Suvarna; Londhe, Rajkumar; Chimanpure, Vaishali; Dhilpe, Veronica; Ghate, Manisha; Yelagate, Rajendra; Panchal, Narayan; Rahane, Girish; Kadam, Dilip; Gaikwad, Nitin; Rewari, Bharat; Gangakhedkar, Raman

2017-07-21

Recent WHO guidelines identify virologic monitoring for diagnosing and confirming ART failure. In view of this, validation and scale up of point of care viral load technologies is essential in resource limited settings. A systematic validation of the GeneXpert® HIV-1 Quant assay (a point-of-care technology) in view of scaling up HIV-1 viral load in India to monitor the success of national ART programme was carried out. Two hundred nineteen plasma specimens falling in nine viral load ranges (5 L copies/ml) were tested by the Abbott m2000rt Real Time and GeneXpert HIV-1 Quant assays. Additionally, 20 seronegative; 16 stored specimens and 10 spiked controls were also tested. Statistical analysis was done using Stata/IC and sensitivity, specificity, PPV, NPV and %misclassification rates were calculated as per DHSs/AISs, WHO, NACO cut-offs for virological failure. The GeneXpert assay compared well with the Abbott assay with a higher sensitivity (97%), specificity (97-100%) and concordance (91.32%). The correlation between two assays (r = 0.886) was statistically significant (p performance and rapidity will aid in timely diagnosis of ART failures, integrated HIV-TB management and will facilitate the UNAIDS 90-90-90 target.

Multiple proviral integration events after virological synapse-mediated HIV-1 spread

International Nuclear Information System (INIS)

Russell, Rebecca A.; Martin, Nicola; Mitar, Ivonne; Jones, Emma; Sattentau, Quentin J.

2013-01-01

HIV-1 can move directly between T cells via virological synapses (VS). Although aspects of the molecular and cellular mechanisms underlying this mode of spread have been elucidated, the outcomes for infection of the target cell remain incompletely understood. We set out to determine whether HIV-1 transfer via VS results in productive, high-multiplicity HIV-1 infection. We found that HIV-1 cell-to-cell spread resulted in nuclear import of multiple proviruses into target cells as seen by fluorescence in-situ hybridization. Proviral integration into the target cell genome was significantly higher than that seen in a cell-free infection system, and consequent de novo viral DNA and RNA production in the target cell detected by quantitative PCR increased over time. Our data show efficient proviral integration across VS, implying the probability of multiple integration events in target cells that drive productive T cell infection. - Highlights: • Cell-to-cell HIV-1 infection delivers multiple vRNA copies to the target cell. • Cell-to-cell infection results in productive infection of the target cell. • Cell-to-cell transmission is more efficient than cell-free HIV-1 infection. • Suggests a mechanism for recombination in cells infected with multiple viral genomes

Performance and Logistical Challenges of Alternative HIV-1 Virological Monitoring Options in a Clinical Setting of Harare, Zimbabwe

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Pascale Ondoa

2014-01-01

Full Text Available We evaluated a low-cost virological failure assay (VFA on plasma and dried blood spot (DBS specimens from HIV-1 infected patients attending an HIV clinic in Harare. The results were compared to the performance of the ultrasensitive heat-denatured p24 assay (p24. The COBAS AmpliPrep/COBAS TaqMan HIV-1 test, version 2.0, served as the gold standard. Using a cutoff of 5,000 copies/mL, the plasma VFA had a sensitivity of 94.5% and specificity of 92.7% and was largely superior to the VFA on DBS (sensitivity = 61.9%; specificity = 99.0% or to the p24 (sensitivity = 54.3%; specificity = 82.3% when tested on 302 HIV treated and untreated patients. However, among the 202 long-term ART-exposed patients, the sensitivity of the VFA decreased to 72.7% and to 35.7% using a threshold of 5,000 and 1,000 RNA copies/mL, respectively. We show that the VFA (either on plasma or on DBS and the p24 are not reliable to monitor long-term treated, HIV-1 infected patients. Moreover, achieving acceptable assay sensitivity using DBS proved technically difficult in a less-experienced laboratory. Importantly, the high level of virological suppression (93% indicated that quality care focused on treatment adherence limits virological failure even when PCR-based viral load monitoring is not available.

Identifying HIV-1 dual infections

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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

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.

Integration of prevention of mother-to-child transmission of HIV (PMTCT postpartum services with other HIV care and treatment services within the maternal and child health setting in Zimbabwe, 2012.

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Katherine Wiegert

Full Text Available We assessed the integration of PMTCT services during the postpartum period including early infant diagnosis of HIV (EID and adult and pediatric antiretroviral therapy (ART in maternal and child health (MCH facilities in Zimbabwe.From August to December 2012 we conducted a cross-sectional survey of a nationally representative sample of 151 MCH facilities. A questionnaire was used to survey each site about staff training, dried blood spot sample (DBS collection, turnaround time (TAT for test results, PMTCT services, and HIV care and treatment linkages for HIV-infected mothers and children and HIV-exposed infants. Descriptive analyses were used. Of the facilities surveyed, all facilities were trained on DBS collection and 92% responded. Approximately, 99% of responding facilities reported providing DBS collection and a basic HIV-exposed infant service package including EID, extended nevirapine prophylaxis, and use of cotrimoxazole. DBS collection was integrated with immunisations at 83% of facilities, CD4 testing with point-of-care machines was available at 37% of facilities, and ART for both mothers and children was provided at 27% of facilities. More than 80% of facilities reported that DBS test results take >4 weeks to return; TAT did not have a direct association with any specific type of transport, distance to the lab, or intermediate stops for data to travel.Zimbabwe has successfully scaled up and integrated the national EID and PMTCT programs into the existing MCH setting. The long TAT of infant DBS test results and the lack of integrated ART programs in the MCH setting could reduce effectiveness of the national PMTCT and ART programs. Addressing these important gaps will support successful implementation of the 2014 Zimbabwe's PMTCT guidelines under which all HIV-infected pregnant and breastfeeding women will be offered life-long ART and decentralized ART care.

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

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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.

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

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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.

HIV risks and HIV prevention among female sex workers in two largest urban settings in Croatia, 2008-2014.

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Štulhofer, Aleksandar; Landripet, Ivan; Božić, Jasmina; Božičević, Ivana

2015-01-01

Harm reduction-based HIV prevention has been in place among female sex workers (FSWs) in Croatia for more than a decade. However, little is known about how well the existing programs meet the needs of FSWs in an environment where sex work remains criminalized and highly stigmatized. This study aims to assess changes in FSWs' vulnerability to HIV infection in the 2008-2014 period. Using convenience samples of FSWs in Croatia's two largest urban settings, behavioral data were collected in 2007-2008 and 2014. Outreach workers interviewed 154 FSWs in the first wave of the survey and 158 in the second. The period under observation was characterized by a stable prevalence of most HIV-relevant risk behaviors and experiences. Significant changes in client-based victimization and HIV knowledge were observed only among FSWs in the capital city. Substantial and mostly sustained levels of sexual and nonsexual victimization call for more research into the limits of the current behavior-based harm reduction approach to HIV prevention in the country.

Relationship between hunger, adherence to antiretroviral therapy and plasma HIV RNA suppression among HIV-positive illicit drug users in a Canadian setting.

Science.gov (United States)

Anema, Aranka; Kerr, Thomas; Milloy, M-J; Feng, Cindy; Montaner, Julio S G; Wood, Evan

2014-04-01

Food insecurity may be a barrier to achieving optimal HIV treatment-related outcomes among illicit drug users. This study therefore, aimed to assess the impact of severe food insecurity, or hunger, on plasma HIV RNA suppression among illicit drug users receiving antiretroviral therapy (ART). A cross-sectional Multivariate logistic regression model was used to assess the potential relationship between hunger and plasma HIV RNA suppression. A sample of n = 406 adults was derived from a community-recruited open prospective cohort of HIV-positive illicit drug users, in Vancouver, British Columbia (BC), Canada. A total of 235 (63.7%) reported "being hungry and unable to afford enough food," and 241 (59.4%) had plasma HIV RNA hunger was associated with lower odds of plasma HIV RNA suppression (Odds Ratio = 0.59, 95% confidence interval [CI]: 0.39-0.90, p = 0.015). In multivariate analyses, this association was no longer significant after controlling for socio-demographic, behavioral, and clinical characteristics, including 95% adherence (Adjusted Odds Ratio [AOR] = 0.65, 95% CI: 0.37-1.10, p = 0.105). Multivariate models stratified by 95% adherence found that the direction and magnitude of this association was not significantly altered by the adherence level. Hunger was common among illicit drug users in this setting. Although, there was an association between hunger and lower likelihood of plasma HIV RNA suppression, this did not persist in adjusted analyses. Further research is warranted to understand the social-structural, policy, and physical factors shaping the HIV outcomes of illicit drug users.

Multicohort Genomewide Association Study Reveals a New Signal of Protection Against HIV-1 Acquisition

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Limou, Sophie; Delaneau, Olivier; van Manen, Daniëlle; An, Ping; Sezgin, Efe; Le Clerc, Sigrid; Coulonges, Cédric; Troyer, Jennifer L.; Veldink, Jan H.; van den Berg, Leonard H.; Spadoni, Jean-Louis; Taing, Lieng; Labib, Taoufik; Montes, Matthieu; Delfraissy, Jean-François; Schachter, François; O’Brien, Stephen J.; Buchbinder, Susan; van Natta, Mark L.; Jabs, Douglas A.; Froguel, Philippe; Schuitemaker, Hanneke; Winkler, Cheryl A.

2012-01-01

Background. To date, only mutations in CCR5 have been shown to confer resistance to human immunodeficiency virus type 1 (HIV-1) infection, and these explain only a small fraction of the observed variability in HIV susceptibility. Methods. We performed a meta-analysis between 2 independent European genomewide association studies, each comparing HIV-1 seropositive cases with normal population controls known to be HIV uninfected, to identify single-nucleotide polymorphisms (SNPs) associated with the HIV-1 acquisition phenotype. SNPs exhibiting P < 10−5 in this first stage underwent second-stage analysis in 2 independent US cohorts of European descent. Results. After the first stage, a single highly significant association was revealed for the chromosome 8 rs6996198 with HIV-1 acquisition and was replicated in both second-stage cohorts. Across the 4 groups, the rs6996198-T allele was consistently associated with a significant reduced risk of HIV-1 infection, and the global meta-analysis reached genomewide significance: Pcombined = 7.76 × 10−8. Conclusions. We provide strong evidence of association for a common variant with HIV-1 acquisition in populations of European ancestry. This protective signal against HIV-1 infection is the first identified outside the CCR5 nexus. First clues point to a potential functional role for a nearby candidate gene, CYP7B1, but this locus warrants further investigation. PMID:22362864

V3-serotyping programme evaluated for HIV-1 variation in the Netherlands and Curacao

NARCIS (Netherlands)

Wolf F de; Akker R van den; Valk M; Bakker M; Goudsmit J; Loon AM van; VIR; UVA/HRL

1995-01-01

To obtain insight into the variation of the HIV-1 V3 neutralization domain of variants circulating in the Netherlands, 126 Dutch, 70 Curacao and 45 African serum samples from HIV-1 infected individuals were screened for antibody reactivity to a set of 16 to 17 mer synthetic peptides, representing

Implementation of evidence-based HIV interventions for young adult African American women in church settings.

Science.gov (United States)

Stewart, Jennifer M

2014-01-01

To assess the barriers and facilitators to using African American churches as sites for implementation of evidence-based HIV interventions among young African American women. Mixed methods cross-sectional design. African American churches in Philadelphia, PA. 142 African American pastors, church leaders, and young adult women ages 18 to 25. Mixed methods convergent parallel design. The majority of young adult women reported engaging in high-risk HIV-related behaviors. Although church leaders reported willingness to implement HIV risk-reduction interventions, they were unsure of how to initiate this process. Key facilitators to the implementation of evidence-based interventions included the perception of the leadership and church members that HIV interventions were needed and that the church was a promising venue for them. A primary barrier to implementation in this setting is the perception that discussions of sexuality should be private. Implementation of evidence-based HIV interventions for young adult African American women in church settings is feasible and needed. Building a level of comfort in discussing matters of sexuality and adapting existing evidence-based interventions to meet the needs of young women in church settings is a viable approach for successful implementation. © 2014 AWHONN, the Association of Women's Health, Obstetric and Neonatal Nurses.

A Grounded Theory Study of HIV-Related Stigma in U.S.-Based Health Care Settings.

Science.gov (United States)

Davtyan, Mariam; Olshansky, Ellen F; Brown, Brandon; Lakon, Cynthia

Despite progress made in the treatment and care of people living with HIV (PLWH), HIV-related stigma has remained persistent. Health care settings and workers have been identified as important sources of stigma. Studies have addressed the construct of stigma in U.S. health care settings, but mainly from the perspectives of PLWH. We used Grounded Theory to understand how health care workers conceptualized HIV-related stigma and to develop a model to project a purposive view of stigma in health care settings. Our model indicates that stigma may be rooted in historically derogatory representations of HIV and intensified by power inequalities. Stigma may be triggered by fear, inadequate clinical education and training, unintentional behaviors, and limited contact with PLWH. Study participants perceived stigma as injurious to patient and provider health outcomes. Additional research on provider perceptions of stigma and programs that encourage empowerment, communication, and training may be necessary for stigma reduction. Copyright © 2017 Association of Nurses in AIDS Care. Published by Elsevier Inc. All rights reserved.

Financial stress is associated with reduced treatment adherence in HIV-infected adults in a resource-rich setting.

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McAllister, J; Beardsworth, G; Lavie, E; MacRae, K; Carr, A

2013-02-01

Financial stress has been identified as a barrier to antiretroviral adherence, but only in resource- limited settings. Almost half of HIV-infected Australian adults earn no regular income and, despite highly subsidised antiretroviral therapy and universal health care, 3% of HIV-infected Australians cease antiretroviral therapy each year. We studied the relationship between financial stress and treatment adherence in a resource-rich setting. Out-patients attending the HIV clinic at St Vincent's Hospital between November 2010 and May 2011 were invited to complete an anonymous survey including questions relating to costs and adherence. Of 335 HIV-infected patients (95.8% male; mean age 52 years; hepatitis coinfection 9.2%), 65 patients (19.6%) stated that it was difficult or very difficult to meet pharmacy dispensing costs, 49 (14.6%) reported that they had delayed purchasing medication because of pharmacy costs, and 30 (9.0%) reported that they had ceased medication because of pharmacy costs. Of the 65 patients with difficulties meeting pharmacy costs, 19 (29.2%) had ceased medication vs. 11 (4.1%) of the remaining 270 patients (P travel costs to the clinic. Treatment cessation and interruption were both independently associated with difficulty meeting both pharmacy and clinic travel costs. Only 4.9% had been asked if they were having difficulty paying for medication. These are the first data to show that pharmacy dispensing and clinic travel costs may affect treatment adherence in a resource-rich setting. Patients should be asked if financial stress is limiting their treatment adherence. © 2012 British HIV Association.

The impact of HIV and ART on recurrent tuberculosis in a sub-Saharan setting.

Science.gov (United States)

Houben, Rein M G J; Glynn, Judith R; Mboma, Sebastian; Mzemba, Themba; Mwaungulu, Nimrod J; Mwaungulu, Lorren; Mwenibabu, Michael; Mpunga, James; French, Neil; Crampin, Amelia C

2012-11-13

To estimate the impact of antiretroviral therapy (ART) on the incidence of recurrent tuberculosis (TB) in an African population. A long-term population cohort in Karonga District, northern Malawi. Patients who had completed treatment for laboratory-confirmed TB diagnosed since 1996 were visited annually to record vital status, ART use and screen for TB. Survival analysis estimated the effect of HIV/ART status at completion of treatment on mortality and recurrence. Analyses were stratified by time since treatment completion to estimate the effects on relapse (predominates during first year) and reinfection disease (predominates later). Among 1133 index TB cases contributing 4353 person-years of follow-up, there were 307 deaths and 103 laboratory-confirmed recurrences (recurrence rate 4.6 per 100 person-years). Half the recurrences occurred in the first year since completing treatment. HIV infection increased the recurrence rate [rate ratio adjusted for age, sex, period and TB type 2.69, 95% confidence interval (CI) 1.69-4.26], but with less effect in the first year (adjusted rate ratio 1.71, 95% CI 0.87-3.35) than subsequently (adjusted rate ratio 4.2, 95% CI 2.16-8.15). Recurrence rates on ART were intermediate between those of HIV-negative individuals and HIV-positive individuals without ART. Compared with HIV-positive individuals without ART, the adjusted rate ratio was 0.74 (95% CI 0.27-2.06) in the first year, and 0.43 (95% CI 0.11-1.73) later. The increased incidence of TB recurrence observed in HIV-positive patients appeared to be reduced by ART. The effects are mostly on later (likely reinfection) disease so the impact of ART on reducing recurrence will be highest in high TB incidence settings.

Defective proviruses rapidly accumulate during acute HIV-1 infection

Science.gov (United States)

Bruner, Katherine M.; Murray, Alexandra J.; Pollack, Ross A.; Soliman, Mary G.; Laskey, Sarah B.; Capoferri, Adam A.; Lai, Jun; Strain, Matthew C.; Lada, Steven M.; Hoh, Rebecca; Ho, Ya-Chi; Richman, Douglas D.; Deeks, Steven G.; Siliciano, Janet D.; Siliciano, Robert F.

2016-01-01

Although antiretroviral therapy (ART) suppresses viral replication to clinically undetectable levels, HIV-1 persists in CD4+ T cells in a latent form not targeted by the immune system or ART1–5. This latent reservoir is a major barrier to cure. Many individuals initiate ART during chronic infection, and in this setting, most proviruses are defective6. However, the dynamics of the accumulation and persistence of defective proviruses during acute HIV-1 infection are largely unknown. Here we show that defective proviruses accumulate rapidly within the first few weeks of infection to make up over 93% of all proviruses, regardless of how early ART is initiated. Using an unbiased method to amplify near full-length proviral genomes from HIV-1 infected adults treated at different stages of infection, we demonstrate that early ART initiation limits the size of the reservoir but does not profoundly impact the proviral landscape. This analysis allows us to revise our understanding of the composition of proviral populations and estimate the true reservoir size in individuals treated early vs. late in infection. Additionally, we demonstrate that common assays for measuring the reservoir do not correlate with reservoir size. These findings reveal hurdles that must be overcome to successfully analyze future HIV-1 cure strategies. PMID:27500724

Effects of CCR5-Delta32, CCR2-64I, and SDF-1 3'A alleles on HIV-1 disease progression

DEFF Research Database (Denmark)

Ioannidis, J P; Rosenberg, P S; Goedert, J J

2001-01-01

BACKGROUND: Studies relating certain chemokine and chemokine receptor gene alleles with the outcome of HIV-1 infection have yielded inconsistent results. OBJECTIVE: To examine postulated associations of genetic alleles with HIV-1 disease progression. DESIGN: Meta-analysis of individual-patient data....... SETTING: 19 prospective cohort studies and case-control studies from the United States, Europe, and Australia. PATIENTS: Patients with HIV-1 infection who were of European or African descent. MEASUREMENTS: Time to AIDS, death, and death after AIDS and HIV-1 RNA level at study entry or soon after...... (relative hazard among seroconverters, 0.64 and 0.74; P HIV-1 RNA levels after seroconversion (difference, -0.18 log(10) copies/mL and -0.14 log(10) copies/mL; P

Low rate of mother-to-child transmission of HIV-1 after nevirapine intervention in a pilot public health program in Yaoundé, Cameroon.

Science.gov (United States)

Ayouba, Ahidjo; Tene, Gilbert; Cunin, Patrick; Foupouapouognigni, Yacouba; Menu, Elisabeth; Kfutwah, Anfumbom; Thonnon, Jocelyn; Scarlatti, Gabriella; Monny-Lobé, Marcel; Eteki, Nicole; Kouanfack, Charles; Tardy, Michèle; Leke, Robert; Nkam, Maurice; Nlend, Anne E; Barré-Sinoussi, Françoise; Martin, Paul M V; Nerrienet, Eric

2003-11-01

To determine the percentage of infected children for whom nevirapine (NVP) was used to prevent peripartum mother-to-child transmission (MTCT) of HIV in Yaoundé, Cameroon. The study was a prospective Public Health Pilot Program covering a 3-year period (January 2000-December 2002). Counseled and consenting HIV-1-positive pregnant women were given a single dose of NVP at the onset of labor. Babies were given 2 mg/kg NVP syrup within the first 72 hours of life. NVP-treated children were regularly followed up and examined for HIV-1 infection at 6-8 weeks and 5-6 months through plasma viral load (VL) quantification with the bDNA system. One hundred twenty-three children were diagnosed with perinatal HIV-1 infection at 6-8 weeks and 5-6 months. Thirteen children (10.6% [13/123]; 95% confidence interval, 5.1-16) were infected and presented with high VLs, in general >500,000 copies/mL. Two children had intermediate VLs (between 50 and 3500 copies/mL) at both time points. One hundred seven children (87%) were considered not infected at 6-8 weeks of age. Our results indicate that the HIV-1 MTCT rate 6-8 weeks after NVP administration was not >13% (16/123), thus demonstrating the effectiveness of NVP for lowering the risk of HIV-1 MTCT in real-life settings.

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.

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

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.

Experiences of stigma and discrimination in social and healthcare settings among trans people living with HIV in the UK.

Science.gov (United States)

Hibbert, M; Wolton, A; Crenna-Jennings, W; Benton, L; Kirwan, P; Lut, I; Okala, S; Ross, M; Furegato, M; Nambiar, K; Douglas, N; Roche, J; Jeffries, J; Reeves, I; Nelson, M; Weerawardhana, C; Jamal, Z; Hudson, A; Delpech, V

2018-07-01

The People Living with HIV StigmaSurvey UK 2015 was a community led national survey investigating experiences of people living with HIV in the UK in the past 12 months. Participants aged 18 and over were recruited through over 120 cross-sector community organisations and 46 HIV clinics to complete an anonymous online survey. Trans is an umbrella term which refers to individuals whose current gender identity is different to the gender they were assigned at birth. Trans participants self-identified via gender identity and gender at birth questions. Descriptive analyses of reported experiences in social and health care settings were conducted and multivariate logistic regression analyses were used to identify sociodemographic predictors of reporting being treated differently to non-HIV patients, and being delayed or refused healthcare treatment in the past 12 months. 31 out of 1576 participants (2%) identified as trans (19 trans women, 5 trans men, 2 gender queer/non-binary, 5 other). High levels of social stigma were reported for all participants, with trans participants significantly more likely to report worrying about verbal harassment (39% vs. 23%), and exclusion from family gatherings (23% vs. 9%) in the last 12 months, compared to cisgender participants. Furthermore, 10% of trans participants reported physical assault in the last 12 months, compared to 4% of cisgender participants. Identifying as trans was a predictor of reporting being treated differently to non-HIV patients (48% vs. 30%; aOR 2.61, CI 1.06, 6.42) and being delayed or refused healthcare (41% vs. 16%; aOR 4.58, CI 1.83, 11.44). Trans people living with HIV in the UK experience high levels of stigma and discrimination, including within healthcare settings, which is likely to impact upon health outcomes. Trans-specific education and awareness within healthcare settings could help to improve service provision for this demographic.

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.

Patient- and population-level health consequences of discontinuing antiretroviral therapy in settings with inadequate HIV treatment availability

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Kimmel April D

2012-09-01

Full Text Available Abstract Background In resource-limited settings, HIV budgets are flattening or decreasing. A policy of discontinuing antiretroviral therapy (ART after HIV treatment failure was modeled to highlight trade-offs among competing policy goals of optimizing individual and population health outcomes. Methods In settings with two available ART regimens, we assessed two strategies: (1 continue ART after second-line failure (Status Quo and (2 discontinue ART after second-line failure (Alternative. A computer model simulated outcomes for a single cohort of newly detected, HIV-infected individuals. Projections were fed into a population-level model allowing multiple cohorts to compete for ART with constraints on treatment capacity. In the Alternative strategy, discontinuation of second-line ART occurred upon detection of antiretroviral failure, specified by WHO guidelines. Those discontinuing failed ART experienced an increased risk of AIDS-related mortality compared to those continuing ART. Results At the population level, the Alternative strategy increased the mean number initiating ART annually by 1,100 individuals (+18.7% to 6,980 compared to the Status Quo. More individuals initiating ART under the Alternative strategy increased total life-years by 15,000 (+2.8% to 555,000, compared to the Status Quo. Although more individuals received treatment under the Alternative strategy, life expectancy for those treated decreased by 0.7 years (−8.0% to 8.1 years compared to the Status Quo. In a cohort of treated patients only, 600 more individuals (+27.1% died by 5 years under the Alternative strategy compared to the Status Quo. Results were sensitive to the timing of detection of ART failure, number of ART regimens, and treatment capacity. Although we believe the results robust in the short-term, this analysis reflects settings where HIV case detection occurs late in the disease course and treatment capacity and the incidence of newly detected patients are

Dried blood spot HIV-1 RNA quantification: A useful tool for viral load monitoring among HIV-infected individuals in India

Science.gov (United States)

Neogi, Ujjwal; Gupta, Soham; Rodridges, Rashmi; Sahoo, Pravat Nalini; Rao, Shwetha D.; Rewari, Bharat B.; Shastri, Suresh; De Costa, Ayesha; Shet, Anita

2012-01-01

Background & objectives: Monitoring of HIV-infected individuals on antiretroviral treatment (ART) ideally requires periodic viral load measurements to ascertain adequate response to treatment. While plasma viral load monitoring is widely available in high-income settings, it is rarely used in resource-limited regions because of high cost and need for sophisticated sample transport. Dried blood spot (DBS) as source specimens for viral load measurement has shown promise as an alternative to plasma specimens and is likely to be a useful tool for Indian settings. The present study was undertaken to investigate the performance of DBS in HIV-1 RNA quantification against the standard plasma viral load assay. Methods: Between April-June 2011, 130 samples were collected from HIV-1-infected (n=125) and non-infected (n=5) individuals in two district clinics in southern India. HIV-1 RNA quantification was performed from DBS and plasma using Abbott m2000rt system after manual RNA extraction. Statistical analysis included correlation, regression and Bland-Altman analysis. Results: The sensitivity of DBS viral load was 97 per cent with viral loads >3.0 log10 copies/ml. Measurable viral load (>3.0 log 10 copies/ml) results obtained for the 74 paired plasma-DBS samples showed positive correlation between both the assays (r=0.96). For clinically acceptable viral load threshold values of >5,000 copies/ml, Bland-Altman plots showed acceptable limits of agreement (−0.21 to +0.8 log10 copies/ml). The mean difference was 0.29 log10 copies/ml. The cost of DBS was $2.67 lower compared to conventional plasma viral load measurement in the setting Interpretation & conclusions: The significant positive correlation with standard plasma-based assay and lower cost of DBS viral load monitoring suggest that DBS sampling can be a feasible and economical means of viral load monitoring in HIV-infected individual in India and in other resource-limited settings globally. PMID:23391790

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

Directory of Open Access Journals (Sweden)

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.

Point Set Denoising Using Bootstrap-Based Radial Basis Function.

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Liew, Khang Jie; Ramli, Ahmad; Abd Majid, Ahmad

2016-01-01

This paper examines the application of a bootstrap test error estimation of radial basis functions, specifically thin-plate spline fitting, in surface smoothing. The presence of noisy data is a common issue of the point set model that is generated from 3D scanning devices, and hence, point set denoising is one of the main concerns in point set modelling. Bootstrap test error estimation, which is applied when searching for the smoothing parameters of radial basis functions, is revisited. The main contribution of this paper is a smoothing algorithm that relies on a bootstrap-based radial basis function. The proposed method incorporates a k-nearest neighbour search and then projects the point set to the approximated thin-plate spline surface. Therefore, the denoising process is achieved, and the features are well preserved. A comparison of the proposed method with other smoothing methods is also carried out in this study.

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

Directory of Open Access Journals (Sweden)

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

Impact of intimate partner violence on clinic attendance, viral suppression and CD4 cell count of women living with HIV in an urban clinic setting.

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Anderson, Jocelyn C; Campbell, Jacquelyn C; Glass, Nancy E; Decker, Michele R; Perrin, Nancy; Farley, Jason

2018-04-01

The substance abuse, violence and HIV/AIDS (SAVA) syndemic represents a complex set of social determinants of health that impacts the lives of women. Specifically, there is growing evidence that intimate partner violence (IPV) places women at risk for both HIV acquisition and poorer HIV-related outcomes. This study assessed prevalence of IPV in an HIV clinic setting, as well as the associations between IPV, symptoms of depression and PTSD on three HIV-related outcomes-CD4 count, viral load, and missed clinic visits. In total, 239 adult women attending an HIV-specialty clinic were included. Fifty-one percent (95% CI: 45%-58%) reported past year psychological, physical, or sexual intimate partner abuse. In unadjusted models, IPV was associated with having a CD4 count 33% of past year all type clinic visits (OR: 1.535, 95% CI: 0.920-2.560, p = 0.101) or HIV specialty clinic visits (OR: 1.251, 95% CI: 0.732-2.140). In multivariable regression, controlling for substance use, mental health symptoms and demographic covariates, IPV remained associated with CD4 count suppression. The association between IPV and lower CD4 counts, but not adherence markers such as viral suppression and missed visits, indicates a need to examine potential physiologic impacts of trauma that may alter the immune functioning of women living with HIV. Incorporating trauma-informed approaches into current HIV care settings is one opportunity that begins to address IPV in this patient population.

Quality assurance for HIV point-of-care testing and treatment monitoring assays

Directory of Open Access Journals (Sweden)

Adrienne F.A. Meyers

2016-10-01

Full Text Available In 2015, UNAIDS launched the 90-90-90 targets aimed at increasing the number of peopleinfected with HIV to become aware of their status, access antiretroviral therapies and ultimatelybe virally suppressed. To achieve these goals, countries may need to scale up point-of-care (POC testing in addition to strengthening central laboratory services. While decentralisingtesting increases patient access to diagnostics, it presents many challenges with regard totraining and assuring the quality of tests and testing. To ensure synergies, the London Schoolof Hygiene & Tropical Medicine held a series of consultations with countries with an interestin quality assurance and their implementing partners, and agreed on an external qualityassessment (EQA programme to ensure reliable results so that the results lead to the bestpossible care for HIV patients. As a result of the consultations, EQA International wasestablished, bringing together EQA providers and implementers to develop a strategic planfor countries to establish national POC EQA programmes and to estimate the cost of setting upand maintaining the programme. With the dramatic increase in the number of proficiencytesting panels required for thousands of POC testing sites across Africa, it is important tofacilitate technology transfer from global EQA providers to a network of regional EQA centresin Africa for regional proficiency testing panel production. EQA International will continue toidentify robust and cost-effective EQA technologies for quality POC testing, integrating noveltechnologies to support sustainable country-owned EQA programmes in Africa.

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.

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

Directory of Open Access Journals (Sweden)

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.

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

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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.

Expanded breadth of the T-cell response to mosaic HIV-1 envelope DNA vaccination

Energy Technology Data Exchange (ETDEWEB)

Korber, Bette [Los Alamos National Laboratory; Fischer, William [Los Alamos National Laboratory; Wallstrom, Timothy [Los Alamos National Laboratory

2009-01-01

An effective AIDS vaccine must control highly diverse circulating strains of HIV-1. Among HIV -I gene products, the envelope (Env) protein contains variable as well as conserved regions. In this report, an informatic approach to the design of T-cell vaccines directed to HIV -I Env M group global sequences was tested. Synthetic Env antigens were designed to express mosaics that maximize the inclusion of common potential Tcell epitope (PTE) 9-mers and minimize the inclusion of rare epitopes likely to elicit strain-specific responses. DNA vaccines were evaluated using intracellular cytokine staining (ICS) in inbred mice with a standardized panel of highly conserved 15-mer PTE peptides. I, 2 and 3 mosaic sets were developed that increased theoretical epitope coverage. The breadth and magnitude ofT-cell immunity stimulated by these vaccines were compared to natural strain Env's; additional comparisons were performed on mutant Env's, including gpl60 or gpl45 with or without V regions and gp41 deletions. Among them, the 2 or 3 mosaic Env sets elicited the optimal CD4 and CD8 responses. These responses were most evident in CD8 T cells; the 3 mosaic set elicited responses to an average of 8 peptide pools compared to 2 pools for a set of3 natural Env's. Synthetic mosaic HIV -I antigens can therefore induce T-cell responses with expanded breadth and may facilitate the development of effective T -cell-based HIV -1 vaccines.

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

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

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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.

Alterations in the nuclear proteome of HIV-1 infected T-cells

International Nuclear Information System (INIS)

DeBoer, Jason; Jagadish, Teena; Haverland, Nicole A.; Madson, Christian J.; Ciborowski, Pawel; Belshan, Michael

2014-01-01

Virus infection of a cell involves the appropriation of host factors and the innate defensive response of the cell. The identification of proteins critical for virus replication may lead to the development of novel, cell-based inhibitors. In this study we mapped the changes in T-cell nuclei during human immunodeficiency virus type 1 (HIV-1) at 20 hpi. Using a stringent data threshold, a total of 13 and 38 unique proteins were identified in infected and uninfected cells, respectively, across all biological replicates. An additional 15 proteins were found to be differentially regulated between infected and control nuclei. STRING analysis identified four clusters of protein–protein interactions in the data set related to nuclear architecture, RNA regulation, cell division, and cell homeostasis. Immunoblot analysis confirmed the differential expression of several proteins in both C8166-45 and Jurkat E6-1 T-cells. These data provide a map of the response in host cell nuclei upon HIV-1 infection. - Highlights: • We identify changes in the expression of nuclear proteins during HIV-1 infection. • 163 nuclear proteins were found differentially regulated during HIV-1 infection. • Bioinformatic analysis identified several nuclear pathways altered by HIV infection. • Candidate factors were validated in two independent cell lines

Alterations in the nuclear proteome of HIV-1 infected T-cells

Energy Technology Data Exchange (ETDEWEB)

DeBoer, Jason [Department of Medical Microbiology and Immunology, Creighton University, 2500 California Plaza, Omaha, NE 68178 (United States); Jagadish, Teena; Haverland, Nicole A. [Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE 68198 (United States); Madson, Christian J. [Department of Medical Microbiology and Immunology, Creighton University, 2500 California Plaza, Omaha, NE 68178 (United States); Ciborowski, Pawel [Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE 68198 (United States); The Nebraska Center for Virology, University of Nebraska, Lincoln 68583 (United States); Belshan, Michael, E-mail: michaelbelshan@creighton.edu [Department of Medical Microbiology and Immunology, Creighton University, 2500 California Plaza, Omaha, NE 68178 (United States); The Nebraska Center for Virology, University of Nebraska, Lincoln 68583 (United States)

2014-11-15

Virus infection of a cell involves the appropriation of host factors and the innate defensive response of the cell. The identification of proteins critical for virus replication may lead to the development of novel, cell-based inhibitors. In this study we mapped the changes in T-cell nuclei during human immunodeficiency virus type 1 (HIV-1) at 20 hpi. Using a stringent data threshold, a total of 13 and 38 unique proteins were identified in infected and uninfected cells, respectively, across all biological replicates. An additional 15 proteins were found to be differentially regulated between infected and control nuclei. STRING analysis identified four clusters of protein–protein interactions in the data set related to nuclear architecture, RNA regulation, cell division, and cell homeostasis. Immunoblot analysis confirmed the differential expression of several proteins in both C8166-45 and Jurkat E6-1 T-cells. These data provide a map of the response in host cell nuclei upon HIV-1 infection. - Highlights: • We identify changes in the expression of nuclear proteins during HIV-1 infection. • 163 nuclear proteins were found differentially regulated during HIV-1 infection. • Bioinformatic analysis identified several nuclear pathways altered by HIV infection. • Candidate factors were validated in two independent cell lines.

Efficient triangulation of Poisson-disk sampled point sets

KAUST Repository

Guo, Jianwei

2014-05-06

In this paper, we present a simple yet efficient algorithm for triangulating a 2D input domain containing a Poisson-disk sampled point set. The proposed algorithm combines a regular grid and a discrete clustering approach to speedup the triangulation. Moreover, our triangulation algorithm is flexible and performs well on more general point sets such as adaptive, non-maximal Poisson-disk sets. The experimental results demonstrate that our algorithm is robust for a wide range of input domains and achieves significant performance improvement compared to the current state-of-the-art approaches. © 2014 Springer-Verlag Berlin Heidelberg.

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

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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

Point Set Denoising Using Bootstrap-Based Radial Basis Function.

Directory of Open Access Journals (Sweden)

Khang Jie Liew

Full Text Available This paper examines the application of a bootstrap test error estimation of radial basis functions, specifically thin-plate spline fitting, in surface smoothing. The presence of noisy data is a common issue of the point set model that is generated from 3D scanning devices, and hence, point set denoising is one of the main concerns in point set modelling. Bootstrap test error estimation, which is applied when searching for the smoothing parameters of radial basis functions, is revisited. The main contribution of this paper is a smoothing algorithm that relies on a bootstrap-based radial basis function. The proposed method incorporates a k-nearest neighbour search and then projects the point set to the approximated thin-plate spline surface. Therefore, the denoising process is achieved, and the features are well preserved. A comparison of the proposed method with other smoothing methods is also carried out in this study.

Improved therapy-success prediction with GSS estimated from clinical HIV-1 sequences.

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Pironti, Alejandro; Pfeifer, Nico; Kaiser, Rolf; Walter, Hauke; Lengauer, Thomas

2014-01-01

Rules-based HIV-1 drug-resistance interpretation (DRI) systems disregard many amino-acid positions of the drug's target protein. The aims of this study are (1) the development of a drug-resistance interpretation system that is based on HIV-1 sequences from clinical practice rather than hard-to-get phenotypes, and (2) the assessment of the benefit of taking all available amino-acid positions into account for DRI. A dataset containing 34,934 therapy-naïve and 30,520 drug-exposed HIV-1 pol sequences with treatment history was extracted from the EuResist database and the Los Alamos National Laboratory database. 2,550 therapy-change-episode baseline sequences (TCEB) were assigned to test set A. Test set B contains 1,084 TCEB from the HIVdb TCE repository. Sequences from patients absent in the test sets were used to train three linear support vector machines to produce scores that predict drug exposure pertaining to each of 20 antiretrovirals: the first one uses the full amino-acid sequences (DEfull), the second one only considers IAS drug-resistance positions (DEonlyIAS), and the third one disregards IAS drug-resistance positions (DEnoIAS). For performance comparison, test sets A and B were evaluated with DEfull, DEnoIAS, DEonlyIAS, geno2pheno[resistance], HIVdb, ANRS, HIV-GRADE, and REGA. Clinically-validated cut-offs were used to convert the continuous output of the first four methods into susceptible-intermediate-resistant (SIR) predictions. With each method, a genetic susceptibility score (GSS) was calculated for each therapy episode in each test set by converting the SIR prediction for its compounds to integer: S=2, I=1, and R=0. The GSS were used to predict therapy success as defined by the EuResist standard datum definition. Statistical significance was assessed using a Wilcoxon signed-rank test. A comparison of the therapy-success prediction performances among the different interpretation systems for test set A can be found in Table 1, while those for test set

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.

Protocol for a randomised controlled implementation trial of point-of-care viral load testing and task shifting: the Simplifying HIV TREAtment and Monitoring (STREAM) study.

Science.gov (United States)

Dorward, Jienchi; Garrett, Nigel; Quame-Amaglo, Justice; Samsunder, Natasha; Ngobese, Hope; Ngomane, Noluthando; Moodley, Pravikrishnen; Mlisana, Koleka; Schaafsma, Torin; Donnell, Deborah; Barnabas, Ruanne; Naidoo, Kogieleum; Abdool Karim, Salim; Celum, Connie; Drain, Paul K

2017-09-27

Achieving the Joint United Nations Programme on HIV and AIDS 90-90-90 targets requires models of HIV care that expand antiretroviral therapy (ART) coverage without overburdening health systems. Point-of-care (POC) viral load (VL) testing has the potential to efficiently monitor ART treatment, while enrolled nurses may be able to provide safe and cost-effective chronic care for stable patients with HIV. This study aims to demonstrate whether POC VL testing combined with task shifting to enrolled nurses is non-inferior and cost-effective compared with laboratory-based VL monitoring and standard HIV care. The STREAM (Simplifying HIV TREAtment and Monitoring) study is an open-label, non-inferiority, randomised controlled implementation trial. HIV-positive adults, clinically stable at 6 months after ART initiation, will be recruited in a large urban clinic in South Africa. Approximately 396 participants will be randomised 1:1 to receive POC HIV VL monitoring and potential task shifting to enrolled nurses, versus laboratory VL monitoring and standard South African HIV care. Initial clinic follow-up will be 2-monthly in both arms, with VL testing at enrolment, 6 months and 12 months. At 6 months (1 year after ART initiation), stable participants in both arms will qualify for a differentiated care model involving decentralised ART pickup at community-based pharmacies. The primary outcome is retention in care and virological suppression at 12 months from enrolment. Secondary outcomes include time to appropriate entry into the decentralised ART delivery programme, costs per virologically suppressed patient and cost-effectiveness of the intervention compared with standard care. Findings will inform the scale up of VL testing and differentiated care in HIV-endemic resource-limited settings. Ethical approval has been granted by the University of KwaZulu-Natal Biomedical Research Ethics Committee (BFC296/16) and University of Washington Institutional Review Board (STUDY

Extreme simplification and rendering of point sets using algebraic multigrid

NARCIS (Netherlands)

Reniers, D.; Telea, A.C.

2009-01-01

We present a novel approach for extreme simplification of point set models, in the context of real-time rendering. Point sets are often rendered using simple point primitives, such as oriented discs. However, this requires using many primitives to render even moderately simple shapes. Often, one

Extreme Simplification and Rendering of Point Sets using Algebraic Multigrid

NARCIS (Netherlands)

Reniers, Dennie; Telea, Alexandru

2005-01-01

We present a novel approach for extreme simplification of point set models in the context of real-time rendering. Point sets are often rendered using simple point primitives, such as oriented discs. However efficient, simple primitives are less effective in approximating large surface areas. A large

Barriers to access prevention of mother-to-child transmission for HIV positive women in a well-resourced setting in Vietnam

Directory of Open Access Journals (Sweden)

Wright Pamela

2008-04-01

Full Text Available Abstract Background According to Vietnamese policy, HIV-infected women should have access at least to HIV testing and Nevirapine prophylaxis, or where available, to adequate counselling, HIV infection staging, ARV prophylaxis, and infant formula. Many studies in high HIV prevalence settings have reported low coverage of PMTCT services, but there have been few reports from low HIV prevalence settings, such as Asian countries. We investigated the access of HIV-infected pregnant women to PMTCT services in the well-resourced setting of the capital city, Hanoi. Methods Fifty-two HIV positive women enrolled in a self-help group in Hanoi were consulted, through in-depth interviews and bi-weekly meetings, about their experiences in accessing PMTCT services. Results Only 44% and 20% of the women had received minimal and comprehensive PMTCT services, respectively. Nine women did not receive any services. Twenty-two women received no counselling. The women reported being limited by lack of knowledge and information due to poor counselling, gaps in PMTCT services, and fear of stigma and discrimination. HIV testing was done too late for optimal interventions and poor quality of care by health staff was frequently mentioned. Conclusion In a setting where PMTCT is available, HIV-infected women and children did not receive adequate care because of barriers to accessing those services. The results suggest key improvements would be improving quality of counselling and making PMTCT guidelines available to health services. Women should receive early HIV testing with adequate counselling, safe care and prophylaxis in a positive atmosphere towards HIV-infected women.

HIV-related stigma and psychological distress: the harmful effects of specific stigma manifestations in various social settings.

Science.gov (United States)

Stutterheim, Sarah E; Pryor, John B; Bos, Arjan E R; Hoogendijk, Robert; Muris, Peter; Schaalma, Herman P

2009-11-13

Recent research has shown that experiences of stigmatization have an adverse impact on the psychological well being of people living with HIV/AIDS (PLWHA). Most studies investigating this relationship employ an aggregate measure of stigma. Although this approach provides useful information about the psychological implications of HIV-related stigma in general, it neglects to acknowledge the possibility that some manifestations in specific settings may be psychologically more detrimental than others. The present study examines which specific stigma experiences are most strongly related to psychological distress across a number of social settings. A cross-sectional survey was administered to 667 PLWHA in the Netherlands. We examined participants' experiences of 11 manifestations of HIV-related stigma in six social settings. Linear regression analyses were conducted to determine which setting-specific manifestations best predict psychological distress after controlling for marital status, education and health status. Three manifestations in family settings, namely receiving advice to conceal one's status, being avoided and being treated with exaggerated kindness, and one manifestation in healthcare settings, namely awkward social interaction, best predicted psychological distress in PLWHA. Manifestations of HIV-related stigma vary according to setting. Certain manifestations in specific social settings impact the psychological well being of PLWHA more than others. In this study, certain experiences of stigmatization with PLWHA's families and in healthcare settings were more strongly related to psychological distress than experiences occurring in other social settings. These findings suggest that stigma reduction interventions focusing on these influential settings may benefit the psychological well being of PLWHA.

Global trends in antiretroviral resistance in treatment-naive individuals with HIV after rollout of antiretroviral treatment in resource-limited settings: a global collaborative study and meta-regression analysis

NARCIS (Netherlands)

Gupta, Ravindra K.; Jordan, Michael R.; Sultan, Binta J.; Hill, Andrew; Davis, Daniel H. J.; Gregson, John; Sawyer, Anthony W.; Hamers, Raph L.; Ndembi, Nicaise; Pillay, Deenan; Bertagnolio, Silvia

2012-01-01

Background The emergence and spread of high levels of HIV-1 drug resistance in resource-limited settings where combination antiretroviral treatment has been scaled up could compromise the effectiveness of national HIV treatment programmes. We aimed to estimate changes in the prevalence of HIV-1 drug

Growth patterns reflect response to antiretroviral therapy in HIV-positive infants: potential utility in resource-poor settings.

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Benjamin, D K; Miller, W C; Ryder, R W; Weber, D J; Walter, E; McKinney, R E

2004-01-01

Laboratory monitoring of HIV-infected children is the current standard of care in the United States to guide the appropriate use of antiretroviral therapy (ART). Although ART is becoming a reality in some developing countries, laboratory monitoring of ART is costly, necessitating creative approaches to monitoring. As an initial step to guide monitoring of HIV progression in low resource settings, we assessed the utility of the physical examination to predict clinical progression of HIV. We conducted a retrospective cohort study of HIV-infected children using data from Pediatric AIDS Clinical Trials Group Protocol 300. We developed a clinical predictive model, and compared the utility of the clinical model to the change in HIV RNA viral load as diagnostic tests of ART failure. The clinical model incorporated treatment regimen, age, and height velocity: a three-level clinical predictive model provided likelihood ratios of 0.3, 3.9, and 14. For decline in RNA the likelihood ratios were 0.2 (> 1 log decline), 1.4, and 3.5 (> log increase). We developed a simple clinical predictive model that was able to predict clinical progression of HIV after initiation of new ART. The clinical model performed similarly to using changes in HIV RNA viral load. These data should be validated internationally and prospectively, because the test subjects were from a resource rich environment and growth patterns in undernourished children may be impacted differently by HIV and its treatment. The model was most pertinent to children 36 months of age or younger, and was conducted in children receiving monotherapy and dual therapy.

Therapeutic doses of irradiation activate viral transcription and induce apoptosis in HIV-1 infected cells

International Nuclear Information System (INIS)

Iordanskiy, Sergey; Van Duyne, Rachel; Sampey, Gavin C; Woodson, Caitlin M; Fry, Kelsi; Saifuddin, Mohammed; Guo, Jia; Wu, Yuntao; Romerio, Fabio; Kashanchi, Fatah

2015-01-01

The highly active antiretroviral therapy reduces HIV-1 RNA in plasma to undetectable levels. However, the virus continues to persist in the long-lived resting CD4"+ T cells, macrophages and astrocytes which form a viral reservoir in infected individuals. Reactivation of viral transcription is critical since the host immune response in combination with antiretroviral therapy may eradicate the virus. Using the chronically HIV-1 infected T lymphoblastoid and monocytic cell lines, primary quiescent CD4"+ T cells and humanized mice infected with dual-tropic HIV-1 89.6, we examined the effect of various X-ray irradiation (IR) doses (used for HIV-related lymphoma treatment and lower doses) on HIV-1 transcription and viability of infected cells. Treatment of both T cells and monocytes with IR, a well-defined stress signal, led to increase of HIV-1 transcription, as evidenced by the presence of RNA polymerase II and reduction of HDAC1 and methyl transferase SUV39H1 on the HIV-1 promoter. This correlated with the increased GFP signal and elevated level of intracellular HIV-1 RNA in the IR-treated quiescent CD4"+ T cells infected with GFP-encoding HIV-1. Exposition of latently HIV-1infected monocytes treated with PKC agonist bryostatin 1 to IR enhanced transcription activation effect of this latency-reversing agent. Increased HIV-1 replication after IR correlated with higher cell death: the level of phosphorylated Ser46 in p53, responsible for apoptosis induction, was markedly higher in the HIV-1 infected cells following IR treatment. Exposure of HIV-1 infected humanized mice with undetectable viral RNA level to IR resulted in a significant increase of HIV-1 RNA in plasma, lung and brain tissues. Collectively, these data point to the use of low to moderate dose of IR alone or in combination with HIV-1 transcription activators as a potential application for the “Shock and Kill” strategy for latently HIV-1 infected cells. - Highlights: • X-ray irradiation (IR) increases

Therapeutic doses of irradiation activate viral transcription and induce apoptosis in HIV-1 infected cells

Energy Technology Data Exchange (ETDEWEB)

Iordanskiy, Sergey [School of Systems Biology, Laboratory of Molecular Virology, George Mason University, Manassas, VA 20110 (United States); Van Duyne, Rachel [School of Systems Biology, Laboratory of Molecular Virology, George Mason University, Manassas, VA 20110 (United States); Center for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, MD 21702 (United States); Sampey, Gavin C; Woodson, Caitlin M; Fry, Kelsi; Saifuddin, Mohammed; Guo, Jia; Wu, Yuntao [School of Systems Biology, Laboratory of Molecular Virology, George Mason University, Manassas, VA 20110 (United States); Romerio, Fabio [Department of Medicine, University of Maryland School of Medicine, Baltimore, MD 21201 (United States); Kashanchi, Fatah, E-mail: fkashanc@gmu.edu [School of Systems Biology, Laboratory of Molecular Virology, George Mason University, Manassas, VA 20110 (United States)

2015-11-15

The highly active antiretroviral therapy reduces HIV-1 RNA in plasma to undetectable levels. However, the virus continues to persist in the long-lived resting CD4{sup +} T cells, macrophages and astrocytes which form a viral reservoir in infected individuals. Reactivation of viral transcription is critical since the host immune response in combination with antiretroviral therapy may eradicate the virus. Using the chronically HIV-1 infected T lymphoblastoid and monocytic cell lines, primary quiescent CD4{sup +} T cells and humanized mice infected with dual-tropic HIV-1 89.6, we examined the effect of various X-ray irradiation (IR) doses (used for HIV-related lymphoma treatment and lower doses) on HIV-1 transcription and viability of infected cells. Treatment of both T cells and monocytes with IR, a well-defined stress signal, led to increase of HIV-1 transcription, as evidenced by the presence of RNA polymerase II and reduction of HDAC1 and methyl transferase SUV39H1 on the HIV-1 promoter. This correlated with the increased GFP signal and elevated level of intracellular HIV-1 RNA in the IR-treated quiescent CD4{sup +} T cells infected with GFP-encoding HIV-1. Exposition of latently HIV-1infected monocytes treated with PKC agonist bryostatin 1 to IR enhanced transcription activation effect of this latency-reversing agent. Increased HIV-1 replication after IR correlated with higher cell death: the level of phosphorylated Ser46 in p53, responsible for apoptosis induction, was markedly higher in the HIV-1 infected cells following IR treatment. Exposure of HIV-1 infected humanized mice with undetectable viral RNA level to IR resulted in a significant increase of HIV-1 RNA in plasma, lung and brain tissues. Collectively, these data point to the use of low to moderate dose of IR alone or in combination with HIV-1 transcription activators as a potential application for the “Shock and Kill” strategy for latently HIV-1 infected cells. - Highlights: • X-ray irradiation

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.

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.

Interventions to reduce risky sexual behaviour for preventing HIV infection in workers in occupational settings.

Science.gov (United States)

Ojo, Olumuyiwa; Verbeek, Jos H; Rasanen, Kimmo; Heikkinen, Jarmo; Isotalo, Leena K; Mngoma, Nomusa; Ruotsalainen, Eija

2011-12-07

The workplace provides an important avenue to prevent HIV. To evaluate the effect of behavioral interventions for reducing HIV on high risk sexual behavior when delivered in an occupational setting. We searched the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE and PsycINFO up until March 2011 and CINAHL, LILACS, DARE, OSH Update, and EPPI database up until October 2010. Randomised control trials (RCTs) in occupational settings or among workers at high risk for HIV that measured HIV, sexual transmitted diseases (STD), Voluntary Counseling and Testing (VCT), or risky sexual behaviour. Two reviewers independently selected studies for inclusion, extracted data and assessed risk of bias. We pooled studies that were similar. We found 8 RCTs with 11,164 participants but one study did not provide enough data. Studies compared VCT to no VCT and education to no intervention and to alternative education.VCT uptake increased to 51% when provided at the workplace compared to a voucher for VCT (RR=14.0 (95% CI 11.8 to16.7)). After VCT, self-reported STD decreased (RR = 0.10 (95% CI 0.01 to 0.73)) but HIV incidence (RR=1.4 (95% CI 0.7 to 2.7)) and unprotected sex (RR=0.71 (0.48 to 1.06)) did not decrease significantly. .Education reduced STDs (RR = 0.68 (95%CI 0.48 to 0.96)), unprotected sex (Standardised Mean Difference (SMD)= -0.17 (95% CI -0.29 to -0.05), sex with a commercial sex worker (RR = 0.88 (95% CI 0.81 to 0.96) but not multiple sexual partners (Mean Difference (MD) = -0.22 (95% CI -0.52 to 0.08) nor use of alcohol before sex (MD = -0.01 (95% CI of -0.11 to 0.08). Workplace interventions to prevent HIV are feasible. There is moderate quality evidence that VCT offered at the work site increases the uptake of testing. Even though this did no lower HIV-incidence, there was a decrease in self-reported sexual transmitted diseases and a decrease in risky sexual behaviour. There is low quality evidence that educational interventions decrease sexually

Incidence of tuberculosis meningitis in a high HIV prevalence setting: time-series analysis from 2006 to 2011.

Science.gov (United States)

Chaya, S; Dangor, Z; Solomon, F; Nzenze, S A; Izu, A; Madhi, S A

2016-11-01

This study was undertaken at a tertiary hospital in Soweto, a peri-urban low-middle income setting. Mycobacterium tuberculosis meningitis (TBM) is a severe manifestation of extra-pulmonary tuberculosis. To describe the incidence, mortality and clinical features of TBM in human immunodeficiency virus (HIV) infected and non-infected children in South Africa from 2006 to 2011. A retrospective, cross-sectional descriptive study. Electronic databases and individual patient records of all children with a discharge diagnosis of TBM were reviewed to yield incidence rate ratios (IRR) in HIV-infected and non-infected children. Clinical, laboratory and radiological characteristics were compared between HIV-infected and non-infected children with TBM. Overall TBM incidence per 100 000 population in 2006 was 6.9 (95%CI 4.4-10.3) and 9.8 (95%CI 6.9-13.6) in 2009, but had subsequently declined to 3.1 (95%CI 1.6-5.5) by 2011. There was a significant reduction in the IRR of TBM among HIV-infected children (IRR 0.916, P = 0.036). The overall case fatality ratio was 6.7%. Clinical features, cerebrospinal fluid and computed tomography brain findings were similar in HIV-infected and non-infected children. TBM incidence decreased over the study period from 2006 to 2011, and was temporally associated with an increase in the uptake of antiretroviral treatment in HIV-infected individuals.

Engineering Cellular Resistance to HIV-1 Infection In Vivo Using a Dual Therapeutic Lentiviral Vector

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Bryan P Burke

2015-01-01

Full Text Available We described earlier a dual-combination anti-HIV type 1 (HIV-1 lentiviral vector (LVsh5/C46 that downregulates CCR5 expression of transduced cells via RNAi and inhibits HIV-1 fusion via cell surface expression of cell membrane-anchored C46 antiviral peptide. This combinatorial approach has two points of inhibition for R5-tropic HIV-1 and is also active against X4-tropic HIV-1. Here, we utilize the humanized bone marrow, liver, thymus (BLT mouse model to characterize the in vivo efficacy of LVsh5/C46 (Cal-1 vector to engineer cellular resistance to HIV-1 pathogenesis. Human CD34+ hematopoietic stem/progenitor cells (HSPC either nonmodified or transduced with LVsh5/C46 vector were transplanted to generate control and treatment groups, respectively. Control and experimental groups displayed similar engraftment and multilineage hematopoietic differentiation that included robust CD4+ T-cell development. Splenocytes isolated from the treatment group were resistant to both R5- and X4-tropic HIV-1 during ex vivo challenge experiments. Treatment group animals challenged with R5-tropic HIV-1 displayed significant protection of CD4+ T-cells and reduced viral load within peripheral blood and lymphoid tissues up to 14 weeks postinfection. Gene-marking and transgene expression were confirmed stable at 26 weeks post-transplantation. These data strongly support the use of LVsh5/C46 lentiviral vector in gene and cell therapeutic applications for inhibition of HIV-1 infection.

Gender-Specific Combination HIV Prevention for Youth in High-Burden Settings: The MP3 Youth Observational Pilot Study Protocol.

Science.gov (United States)

Buttolph, Jasmine; Inwani, Irene; Agot, Kawango; Cleland, Charles M; Cherutich, Peter; Kiarie, James N; Osoti, Alfred; Celum, Connie L; Baeten, Jared M; Nduati, Ruth; Kinuthia, John; Hallett, Timothy B; Alsallaq, Ramzi; Kurth, Ann E

2017-03-08

Nearly three decades into the epidemic, sub-Saharan Africa (SSA) remains the region most heavily affected by human immunodeficiency virus (HIV), with nearly 70% of the 34 million people living with HIV globally residing in the region. In SSA, female and male youth (15 to 24 years) are at a disproportionately high risk of HIV infection compared to adults. As such, there is a need to target HIV prevention strategies to youth and to tailor them to a gender-specific context. This protocol describes the process for the multi-staged approach in the design of the MP3 Youth pilot study, a gender-specific, combination, HIV prevention intervention for youth in Kenya. The objective of this multi-method protocol is to outline a rigorous and replicable methodology for a gender-specific combination HIV prevention pilot study for youth in high-burden settings, illustrating the triangulated methods undertaken to ensure that age, sex, and context are integral in the design of the intervention. The mixed-methods, cross-sectional, longitudinal cohort pilot study protocol was developed by first conducting a systematic review of the literature, which shaped focus group discussions around prevention package and delivery options, and that also informed age- and sex- stratified mathematical modeling. The review, qualitative data, and mathematical modeling created a triangulated evidence base of interventions to be included in the pilot study protocol. To design the pilot study protocol, we convened an expert panel to select HIV prevention interventions effective for youth in SSA, which will be offered in a mobile health setting. The goal of the pilot study implementation and evaluation is to apply lessons learned to more effective HIV prevention evidence and programming. The combination HIV prevention package in this protocol includes (1) offering HIV testing and counseling for all youth; (2) voluntary medical circumcision and condoms for males; (3) pre-exposure prophylaxis (Pr

Efficacy and Safety of Three Antiretroviral Regimens for Initial Treatment of HIV-1: A Randomized Clinical Trial in Diverse Multinational Settings

Science.gov (United States)

Campbell, Thomas B.; Smeaton, Laura M.; Kumarasamy, N.; Flanigan, Timothy; Klingman, Karin L.; Firnhaber, Cynthia; Grinsztejn, Beatriz; Hosseinipour, Mina C.; Kumwenda, Johnstone; Lalloo, Umesh; Riviere, Cynthia; Sanchez, Jorge; Melo, Marineide; Supparatpinyo, Khuanchai; Tripathy, Srikanth; Martinez, Ana I.; Nair, Apsara; Walawander, Ann; Moran, Laura; Chen, Yun; Snowden, Wendy; Rooney, James F.; Uy, Jonathan; Schooley, Robert T.; De Gruttola, Victor; Hakim, James Gita; Swann, Edith; Barnett, Ronald L.; Brizz, Barbara; Delph, Yvette; Gettinger, Nikki; Mitsuyasu, Ronald T.; Eshleman, Susan; Safren, Steven; Fiscus, Susan A.; Andrade, Adriana; Haas, David W.; Amod, Farida; Berthaud, Vladimir; Bollinger, Robert C.; Bryson, Yvonne; Celentano, David; Chilongozi, David; Cohen, Myron; Collier, Ann C.; Currier, Judith Silverstein; Cu-Uvin, Susan; Eron, Joseph; Flexner, Charles; Gallant, Joel E.; Gulick, Roy M.; Hammer, Scott M.; Hoffman, Irving; Kazembe, Peter; Kumwenda, Newton; Lama, Javier R.; Lawrence, Jody; Maponga, Chiedza; Martinson, Francis; Mayer, Kenneth; Nielsen, Karin; Pendame, Richard B.; Ramratnam, Bharat; Sanne, Ian; Severe, Patrice; Sirisanthana, Thira; Solomon, Suniti; Tabet, Steve; Taha, Taha; van der Horst, Charles; Wanke, Christine; Gormley, Joan; Marcus, Cheryl J.; Putnam, Beverly; Loeliger, Edde; Pappa, Keith A.; Webb, Nancy; Shugarts, David L.; Winters, Mark A.; Descallar, Renard S.; Steele, Joseph; Wulfsohn, Michael; Said, Farideh; Chen, Yue; Martin, John C; Bischofberger, Norbert; Cheng, Andrew; Jaffe, Howard; Sharma, Jabin; Poongulali, S.; Cardoso, Sandra Wagner; Faria, Deise Lucia; Berendes, Sima; Burke, Kelly; Mngqibisa, Rosie; Kanyama, Cecelia; Kayoyo, Virginia; Samaneka, Wadzanai P.; Chisada, Anthony; Faesen, Sharla; Chariyalertsak, Suwat; Santos, Breno; Lira, Rita Alves; Joglekar, Anjali A.; Rosa, Alberto La; Infante, Rosa; Jain, Mamta; Petersen, Tianna; Godbole, Sheela; Dhayarkar, Sampada; Feinberg, Judith; Baer, Jenifer; Pollard, Richard B.; Asmuth, David; Gangakhedkar, Raman R; Gaikwad, Asmita; Ray, M. Graham; Basler, Cathi; Para, Michael F.; Watson, Kathy J.; Taiwo, Babafemi; McGregor, Donna; Balfour, Henry H.; Mullan, Beth; Kim, Ge-Youl; Klebert, Michael K.; Cox, Gary Matthew; Silberman, Martha; Mildvan, Donna; Revuelta, Manuel; Tashima, Karen T.; Patterson, Helen; Geiseler, P. Jan; Santos, Bartolo; Daar, Eric S; Lopez, Ruben; Frarey, Laurie; Currin, David; Haas, David H.; Bailey, Vicki L.; Tebas, Pablo; Zifchak, Larisa; Noel-Connor, Jolene; Torres, Madeline; Sha, Beverly E.; Fritsche, Janice M.; Cespedes, Michelle; Forcht, Janet; O'Brien, William A.; Mogridge, Cheryl; Hurley, Christine; Corales, Roberto; Palmer, Maria; Adams, Mary; Luque, Amneris; Lopez-Detres, Luis; Stroberg, Todd

2012-01-01

Background Antiretroviral regimens with simplified dosing and better safety are needed to maximize the efficiency of antiretroviral delivery in resource-limited settings. We investigated the efficacy and safety of antiretroviral regimens with once-daily compared to twice-daily dosing in diverse areas of the world. Methods and Findings 1,571 HIV-1-infected persons (47% women) from nine countries in four continents were assigned with equal probability to open-label antiretroviral therapy with efavirenz plus lamivudine-zidovudine (EFV+3TC-ZDV), atazanavir plus didanosine-EC plus emtricitabine (ATV+DDI+FTC), or efavirenz plus emtricitabine-tenofovir-disoproxil fumarate (DF) (EFV+FTC-TDF). ATV+DDI+FTC and EFV+FTC-TDF were hypothesized to be non-inferior to EFV+3TC-ZDV if the upper one-sided 95% confidence bound for the hazard ratio (HR) was ≤1.35 when 30% of participants had treatment failure. An independent monitoring board recommended stopping study follow-up prior to accumulation of 472 treatment failures. Comparing EFV+FTC-TDF to EFV+3TC-ZDV, during a median 184 wk of follow-up there were 95 treatment failures (18%) among 526 participants versus 98 failures among 519 participants (19%; HR 0.95, 95% CI 0.72–1.27; p = 0.74). Safety endpoints occurred in 243 (46%) participants assigned to EFV+FTC-TDF versus 313 (60%) assigned to EFV+3TC-ZDV (HR 0.64, CI 0.54–0.76; p<0.001) and there was a significant interaction between sex and regimen safety (HR 0.50, CI 0.39–0.64 for women; HR 0.79, CI 0.62–1.00 for men; p = 0.01). Comparing ATV+DDI+FTC to EFV+3TC-ZDV, during a median follow-up of 81 wk there were 108 failures (21%) among 526 participants assigned to ATV+DDI+FTC and 76 (15%) among 519 participants assigned to EFV+3TC-ZDV (HR 1.51, CI 1.12–2.04; p = 0.007). Conclusion EFV+FTC-TDF had similar high efficacy compared to EFV+3TC-ZDV in this trial population, recruited in diverse multinational settings. Superior safety, especially in HIV-1-infected

Efficacy and safety of three antiretroviral regimens for initial treatment of HIV-1: a randomized clinical trial in diverse multinational settings.

Directory of Open Access Journals (Sweden)

Thomas B Campbell

Full Text Available Antiretroviral regimens with simplified dosing and better safety are needed to maximize the efficiency of antiretroviral delivery in resource-limited settings. We investigated the efficacy and safety of antiretroviral regimens with once-daily compared to twice-daily dosing in diverse areas of the world.1,571 HIV-1-infected persons (47% women from nine countries in four continents were assigned with equal probability to open-label antiretroviral therapy with efavirenz plus lamivudine-zidovudine (EFV+3TC-ZDV, atazanavir plus didanosine-EC plus emtricitabine (ATV+DDI+FTC, or efavirenz plus emtricitabine-tenofovir-disoproxil fumarate (DF (EFV+FTC-TDF. ATV+DDI+FTC and EFV+FTC-TDF were hypothesized to be non-inferior to EFV+3TC-ZDV if the upper one-sided 95% confidence bound for the hazard ratio (HR was ≤1.35 when 30% of participants had treatment failure. An independent monitoring board recommended stopping study follow-up prior to accumulation of 472 treatment failures. Comparing EFV+FTC-TDF to EFV+3TC-ZDV, during a median 184 wk of follow-up there were 95 treatment failures (18% among 526 participants versus 98 failures among 519 participants (19%; HR 0.95, 95% CI 0.72-1.27; p = 0.74. Safety endpoints occurred in 243 (46% participants assigned to EFV+FTC-TDF versus 313 (60% assigned to EFV+3TC-ZDV (HR 0.64, CI 0.54-0.76; p<0.001 and there was a significant interaction between sex and regimen safety (HR 0.50, CI 0.39-0.64 for women; HR 0.79, CI 0.62-1.00 for men; p = 0.01. Comparing ATV+DDI+FTC to EFV+3TC-ZDV, during a median follow-up of 81 wk there were 108 failures (21% among 526 participants assigned to ATV+DDI+FTC and 76 (15% among 519 participants assigned to EFV+3TC-ZDV (HR 1.51, CI 1.12-2.04; p = 0.007.EFV+FTC-TDF had similar high efficacy compared to EFV+3TC-ZDV in this trial population, recruited in diverse multinational settings. Superior safety, especially in HIV-1-infected women, and once-daily dosing of EFV+FTC-TDF are

Kelp diagrams : Point set membership visualization

NARCIS (Netherlands)

Dinkla, K.; Kreveld, van M.J.; Speckmann, B.; Westenberg, M.A.

2012-01-01

We present Kelp Diagrams, a novel method to depict set relations over points, i.e., elements with predefined positions. Our method creates schematic drawings and has been designed to take aesthetic quality, efficiency, and effectiveness into account. This is achieved by a routing algorithm, which

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.

Reevaluation of steam generator level trip set point

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Shim, Yoon Sub; Soh, Dong Sub; Kim, Sung Oh; Jung, Se Won; Sung, Kang Sik; Lee, Joon [Korea Atomic Energy Research Institute, Taejon (Korea, Republic of)

1994-06-01

The reactor trip by the low level of steam generator water accounts for a substantial portion of reactor scrams in a nuclear plant and the feasibility of modification of the steam generator water level trip system of YGN 1/2 was evaluated in this study. The study revealed removal of the reactor trip function from the SG water level trip system is not possible because of plant safety but relaxation of the trip set point by 9 % is feasible. The set point relaxation requires drilling of new holes for level measurement to operating steam generators. Characteristics of negative neutron flux rate trip and reactor trip were also reviewed as an additional work. Since the purpose of the trip system modification for reduction of a reactor scram frequency is not to satisfy legal requirements but to improve plant performance and the modification yields positive and negative aspects, the decision of actual modification needs to be made based on the results of this study and also the policy of a plant owner. 37 figs, 6 tabs, 14 refs. (Author).

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

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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

Evaluation of outpatients with suspected pulmonary tuberculosis in a high HIV prevalence setting in Ethiopia: clinical, diagnostic and epidemiological characteristics.

Science.gov (United States)

Bruchfeld, Judith; Aderaye, Getachew; Palme, Ingela Berggren; Bjorvatn, Bjarne; Britton, Sven; Feleke, Yewenhareg; Källenius, Gunilla; Lindquist, Lars

2002-01-01

In a setting with a high prevalence of HIV we studied (i) the prevalence of pulmonary tuberculosis (PTB) and HIV; (ii) clinical and epidemiological characteristics of PTB; and (iii) the usefulness of standard procedures for diagnosing PTB. Of 509 consecutive outpatients evaluated on clinical suspicion of PTB in Addis Ababa, 33.0% were culture-verified as having PTB. PTB patients, non-TB patients and controls were HIV-1-positive in 57.1%, 38.5% and 8.3% of cases, respectively. Predictors for culture-verified PTB were age infection. Diagnosis of PTB based on clinical symptoms, sputum microscopy for acid-fast bacilli and chest radiography was sensitive (86.7%) but unspecific (64.1%). In HIV-positive patients both sensitivity and specificity were significantly lower (p infections are often misinterpreted as smear-negative PTB. HIV screening is therefore warranted not only in cases of verified TB but also as part of the diagnostic work-up in patients with respiratory symptoms suggestive of PTB. Also, increased awareness of, and improved diagnostic tools for, HIV-related pulmonary infections other than PTB are required, together with algorithms for patients with suspected PTB.

HIV-1 envelope glycoprotein

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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.

Timing of the HIV-1 subtype C epidemic in Ethiopia based on early virus strains and subsequent virus diversification

NARCIS (Netherlands)

Abebe, A.; Lukashov, V. V.; Pollakis, G.; Kliphuis, A.; Fontanet, A. L.; Goudsmit, J.; Rinke de Wit, T. F.

2001-01-01

OBJECTIVE: To trace the introduction of HIV-1 subtype C into Ethiopia based on virus diversification during the epidemic. DESIGN: A set of 474 serum samples obtained in Ethiopia in 1982-1985 was tested for HIV-1. HIV-1 env gp120 V3 and gag or pol regions were sequenced and analysed together with

On the Level Set of a Function with Degenerate Minimum Point

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Yasuhiko Kamiyama

2015-01-01

Full Text Available For n≥2, let M be an n-dimensional smooth closed manifold and f:M→R a smooth function. We set minf(M=m and assume that m is attained by unique point p∈M such that p is a nondegenerate critical point. Then the Morse lemma tells us that if a is slightly bigger than m, f-1(a is diffeomorphic to Sn-1. In this paper, we relax the condition on p from being nondegenerate to being an isolated critical point and obtain the same consequence. Some application to the topology of polygon spaces is also included.

Resource utilization and cost-effectiveness of counselor- vs. provider-based rapid point-of-care HIV screening in the emergency department.

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Rochelle P Walensky

Full Text Available Routine HIV screening in emergency department (ED settings may require dedicated personnel. We evaluated the outcomes, costs and cost-effectiveness of HIV screening when offered by either a member of the ED staff or by an HIV counselor.We employed a mathematical model to extend data obtained from a randomized clinical trial of provider- vs. counselor-based HIV screening in the ED. We compared the downstream survival, costs, and cost-effectiveness of three HIV screening modalities: 1 no screening program; 2 an ED provider-based program; and 3 an HIV counselor-based program. Trial arm-specific data were used for test offer and acceptance rates (provider offer 36%, acceptance 75%; counselor offer 80%, acceptance 71%. Undiagnosed HIV prevalence (0.4% and linkage to care rates (80% were assumed to be equal between the screening modalities. Personnel costs were derived from trial-based resource utilization data. We examined the generalizability of results by conducting sensitivity analyses on offer and acceptance rates, undetected HIV prevalence, and costs.Estimated HIV screening costs in the provider and counselor arms averaged $8.10 and $31.00 per result received. The Provider strategy (compared to no screening had an incremental cost-effectiveness ratio of $58,700/quality-adjusted life year (QALY and the Counselor strategy (compared to the Provider strategy had an incremental cost-effectiveness ratio of $64,500/QALY. Results were sensitive to the relative offer and acceptance rates by strategy and the capacity of providers to target-screen, but were robust to changes in undiagnosed HIV prevalence and programmatic costs.The cost-effectiveness of provider-based HIV screening in an emergency department setting compares favorably to other US screening programs. Despite its additional cost, counselor-based screening delivers just as much return on investment as provider based-screening. Investment in dedicated HIV screening personnel is justified in

Resource utilization and cost-effectiveness of counselor- vs. provider-based rapid point-of-care HIV screening in the emergency department.

Science.gov (United States)

Walensky, Rochelle P; Morris, Bethany L; Reichmann, William M; Paltiel, A David; Arbelaez, Christian; Donnell-Fink, Laurel; Katz, Jeffrey N; Losina, Elena

2011-01-01

Routine HIV screening in emergency department (ED) settings may require dedicated personnel. We evaluated the outcomes, costs and cost-effectiveness of HIV screening when offered by either a member of the ED staff or by an HIV counselor. We employed a mathematical model to extend data obtained from a randomized clinical trial of provider- vs. counselor-based HIV screening in the ED. We compared the downstream survival, costs, and cost-effectiveness of three HIV screening modalities: 1) no screening program; 2) an ED provider-based program; and 3) an HIV counselor-based program. Trial arm-specific data were used for test offer and acceptance rates (provider offer 36%, acceptance 75%; counselor offer 80%, acceptance 71%). Undiagnosed HIV prevalence (0.4%) and linkage to care rates (80%) were assumed to be equal between the screening modalities. Personnel costs were derived from trial-based resource utilization data. We examined the generalizability of results by conducting sensitivity analyses on offer and acceptance rates, undetected HIV prevalence, and costs. Estimated HIV screening costs in the provider and counselor arms averaged $8.10 and $31.00 per result received. The Provider strategy (compared to no screening) had an incremental cost-effectiveness ratio of $58,700/quality-adjusted life year (QALY) and the Counselor strategy (compared to the Provider strategy) had an incremental cost-effectiveness ratio of $64,500/QALY. Results were sensitive to the relative offer and acceptance rates by strategy and the capacity of providers to target-screen, but were robust to changes in undiagnosed HIV prevalence and programmatic costs. The cost-effectiveness of provider-based HIV screening in an emergency department setting compares favorably to other US screening programs. Despite its additional cost, counselor-based screening delivers just as much return on investment as provider based-screening. Investment in dedicated HIV screening personnel is justified in situations

Vitamin A deficiency during pregnancy of HIV infected and non-infected women in tropical settings of Northwest Ethiopia

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Bekele Assegedech

2011-07-01

Full Text Available Abstract Background Vitamin A deficiency (VAD is known to be a major public health problem among women of reproductive age in South East Asia and Africa. In Ethiopia, there are no studies conducted on serum vitamin A status of HIV-infected pregnant women. Therefore, the present study was aimed at determining the level of serum vitamin A and VAD among pregnant women with and without HIV infection in tropical settings of Northwest Ethiopia. Methods In this cross-sectional study, blood samples were collected from 423 pregnant women and from 55 healthy volunteers who visited the University of Gondar Hospital. Serum concentration of vitamin A was measured by high performance liquid chromatography. Results After controlling for total serum protein, albumin and demographic variables, the mean ± SD serum vitamin A in HIV seropositive pregnant women (0.96 ± 0.42 μmol/L was significantly lower than that in pregnant women without HIV infection (1.10 ± 0.45 μmol/L, P Conclusion The present study shows that VAD is a major public health problem among pregnant women in the tropical settings of Northwest Ethiopia. Considering the possible implications of VAD during pregnancy, we recommend multivitamin (which has a lower level of vitamin A supplementation in the care and management of pregnant women with or without HIV infection.

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

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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.

Point-of-care C-reactive protein-based tuberculosis screening for people living with HIV: a diagnostic accuracy study.

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Yoon, Christina; Semitala, Fred C; Atuhumuza, Elly; Katende, Jane; Mwebe, Sandra; Asege, Lucy; Armstrong, Derek T; Andama, Alfred O; Dowdy, David W; Davis, J Luke; Huang, Laurence; Kamya, Moses; Cattamanchi, Adithya

2017-12-01

Symptom-based screening for tuberculosis is recommended for all people living with HIV. This recommendation results in unnecessary Xpert MTB/RIF testing in many individuals living in tuberculosis-endemic areas and thus poor implementation of intensified case finding and tuberculosis preventive therapy. Novel approaches to tuberculosis screening are needed to help achieve global targets for tuberculosis elimination. We assessed the performance of C-reactive protein (CRP) measured with a point-of-care assay as a screening tool for active pulmonary tuberculosis. For this prospective study, we enrolled adults (aged ≥18 years) living with HIV with CD4 cell count less than or equal to 350 cells per μL who were initiating antiretroviral therapy (ART) from two HIV/AIDS clinics in Uganda. CRP concentrations were measured at study entry with a point-of-care assay using whole blood obtained by fingerprick (concentration ≥10 mg/L defined as screen positive for tuberculosis). Sputum samples were collected for Xpert MTB/RIF testing and culture. We calculated the sensitivity and specificity of point-of-care CRP and WHO symptom-based screening in reference to culture results. We repeated the sensitivity analysis with Xpert MTB/RIF as the reference standard. Between July 8, 2013, and Dec 15, 2015, 1237 HIV-infected adults were enrolled and underwent point-of-care CRP testing. 60 (5%) patients with incomplete or contaminated cultures were excluded from the analysis. Of the remaining 1177 patients (median CD4 count 165 cells per μL [IQR 75-271]), 163 (14%) had culture-confirmed tuberculosis. Point-of-care CRP testing had 89% sensitivity (145 of 163, 95% CI 83-93) and 72% specificity (731 of 1014, 95% CI 69-75) for culture-confirmed tuberculosis. Compared with WHO symptom-based screening, point-of-care CRP testing had lower sensitivity (difference -7%, 95% CI -12 to -2; p=0·002) but substantially higher specificity (difference 58%, 95% CI 55 to 61; ptuberculosis screening test

Excision of HIV-1 proviral DNA by recombinant cell permeable tre-recombinase.

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Lakshmikanth Mariyanna

Full Text Available Over the previous years, comprehensive studies on antiretroviral drugs resulted in the successful introduction of highly active antiretroviral therapy (HAART into clinical practice for treatment of HIV/AIDS. However, there is still need for new therapeutic approaches, since HAART cannot eradicate HIV-1 from the infected organism and, unfortunately, can be associated with long-term toxicity and the development of drug resistance. In contrast, novel gene therapy strategies may have the potential to reverse the infection by eradicating HIV-1. For example, expression of long terminal repeat (LTR-specific recombinase (Tre-recombinase has been shown to result in chromosomal excision of proviral DNA and, in consequence, in the eradication of HIV-1 from infected cell cultures. However, the delivery of Tre-recombinase currently depends on the genetic manipulation of target cells, a process that is complicating such therapeutic approaches and, thus, might be undesirable in a clinical setting. In this report we demonstrate that E.coli expressed Tre-recombinases, tagged either with the protein transduction domain (PTD from the HIV-1 Tat trans-activator or the translocation motif (TLM of the Hepatitis B virus PreS2 protein, were able to translocate efficiently into cells and showed significant recombination activity on HIV-1 LTR sequences. Tre activity was observed using episomal and stable integrated reporter constructs in transfected HeLa cells. Furthermore, the TLM-tagged enzyme was able to excise the full-length proviral DNA from chromosomal integration sites of HIV-1-infected HeLa and CEM-SS cells. The presented data confirm Tre-recombinase activity on integrated HIV-1 and provide the basis for the non-genetic transient application of engineered recombinases, which may be a valuable component of future HIV eradication strategies.

Sensitivity of the ViroSeq HIV-1 Genotyping System for Detection of the K103N Resistance Mutation in HIV-1 Subtypes A, C, and D

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Church, Jessica D.; Jones, Dana; Flys, Tamara; Hoover, Donald; Marlowe, Natalia; Chen, Shu; Shi, Chanjuan; Eshleman, James R.; Guay, Laura A.; Jackson, J. Brooks; Kumwenda, Newton; Taha, Taha E.; Eshleman, Susan H.

2006-01-01

The US Food and Drug Administration-cleared ViroSeq HIV-1 Genotyping System (ViroSeq) and other population sequencing-based human immunodeficiency virus type 1 (HIV-1) genotyping methods detect antiretroviral drug resistance mutations present in the major viral population of a test sample. These assays also detect some mutations in viral variants that are present as mixtures. We compared detection of the K103N nevirapine resistance mutation using ViroSeq and a sensitive, quantitative point mutation assay, LigAmp. The LigAmp assay measured the percentage of K103N-containing variants in the viral population (percentage of K103N). We analyzed 305 samples with HIV-1 subtypes A, C, and D collected from African women after nevirapine administration. ViroSeq detected K103N in 100% of samples with >20% K103N, 77.8% of samples with 10 to 20% K103N, 71.4% of samples with 5 to 10% K103N, and 16.9% of samples with 1 to 5% K103N. The sensitivity of ViroSeq for detection of K103N was similar for subtypes A, C, and D. These data indicate that the ViroSeq system reliably detects the K103N mutation at levels above 20% and frequently detects the mutation at lower levels. Further studies are needed to compare the sensitivity of different assays for detection of HIV-1 drug resistance mutations and to determine the clinical relevance of HIV-1 minority variants. PMID:16931582

Comparative evaluation of Amplicor HIV-1 DNA test, version 1.5, by ...

African Journals Online (AJOL)

Human immunodeficiency virus (HIV) DNA polymerase chain reaction (PCR) test using venous blood sample has been used for many years in low resource settings for early infant diagnosis of HIV infection in children less than 18 months. The aim of this study was to evaluate and compare the performance characteristics of ...

Developing a Dynamic Pharmacophore Model for HIV-1 Integrase

International Nuclear Information System (INIS)

Carlson, Heather A.; Masukawa, Keven M.; Rubins, Kathleen; Bushman, Frederic; Jorgensen, William L.; Lins, Roberto; Briggs, James; Mccammon, Andy

2000-01-01

We present the first receptor-based pharmacophore model for HIV-1 integrase. The development of ''dynamic'' pharmacophore models is a new method that accounts for the inherent flexibility of the active site and aims to reduce the entropic penalties associated with binding a ligand. Furthermore, this new drug discovery method overcomes the limitation of an incomplete crystal structure of the target protein. A molecular dynamics (MD) simulation describes the flexibility of the uncomplexed protein. Many conformational models of the protein are saved from the MD simulations and used in a series of multi-unit search for interacting conformers (MUSIC) simulations. MUSIC is a multiple-copy minimization method, available in the BOSS program; it is used to determine binding regions for probe molecules containing functional groups that complement the active site. All protein conformations from the MD are overlaid, and conserved binding regions for the probe molecules are identified. Those conserved binding regions define the dynamic pharmacophore model. Here, the dynamic model is compared to known inhibitors of the integrase as well as a three-point, ligand-based pharmacophore model from the literature. Also, a ''static'' pharmacophore model was determined in the standard fashion, using a single crystal structure. Inhibitors thought to bind in the active site of HIV-1 integrase fit the dynamic model but not the static model. Finally, we have identified a set of compounds from the Available Chemicals Directory that fit the dynamic pharmacophore model, and experimental testing of the compounds has confirmed several new inhibitors

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

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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.

Inhibition of HIV-1 entry by extracts derived from traditional Chinese medicinal herbal plants

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Song Xinming

2009-08-01

HIV-1 interaction with target cells, i.e., the interaction between gp120 and CD4/CCR5 or gp120 and CD4/CXCR4 and point to the potential of developing these two extracts to be HIV-1 entry inhibitors.

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

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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.

Quality assurance for HIV point-of-care testing and treatment monitoring assays

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Sandstrom, Paul; Denny, Thomas N.; Hurlston, Mackenzie; Ball, Terry B.; Peeling, Rosanna W.; Boeras, Debrah I.

2016-01-01

In 2015, UNAIDS launched the 90-90-90 targets aimed at increasing the number of people infected with HIV to become aware of their status, access antiretroviral therapies and ultimately be virally suppressed. To achieve these goals, countries may need to scale up point-of-care (POC) testing in addition to strengthening central laboratory services. While decentralising testing increases patient access to diagnostics, it presents many challenges with regard to training and assuring the quality of tests and testing. To ensure synergies, the London School of Hygiene & Tropical Medicine held a series of consultations with countries with an interest in quality assurance and their implementing partners, and agreed on an external quality assessment (EQA) programme to ensure reliable results so that the results lead to the best possible care for HIV patients. As a result of the consultations, EQA International was established, bringing together EQA providers and implementers to develop a strategic plan for countries to establish national POC EQA programmes and to estimate the cost of setting up and maintaining the programme. With the dramatic increase in the number of proficiency testing panels required for thousands of POC testing sites across Africa, it is important to facilitate technology transfer from global EQA providers to a network of regional EQA centres in Africa for regional proficiency testing panel production. EQA International will continue to identify robust and cost-effective EQA technologies for quality POC testing, integrating novel technologies to support sustainable country-owned EQA programmes in Africa. PMID:28879133

Access and management of HIV-related diseases in resource-constrained settings: a workshop report.

Science.gov (United States)

Dimba, Eao; Yengopal, V; Joshua, E; Thavarajah, R; Balasundaram, S

2016-04-01

With advancement of medical interventions, the lifespan of people living with HIV has increased globally. However, low- and middle-income countries (LMICs) which bear the greatest burden of the HIV pandemic face a constant challenge in addressing the treatment needs of immune-suppressed patients. An analysis of the current management protocols and access to medication in resource-poor settings was conducted at this workshop, with emphasis on the situation in resource-poor settings. The participants developed a consensus document based on the need to respond to the constantly changing HIV pandemic. Provision of oral health care must be guided by interconnecting principles based on population based strategies that address upstream determinants of health. Basic oral health coverage in developing countries can only be realized with a strong foundation at the primary health level. Early diagnosis of HIV-related comorbidities including the adverse effects of ARVs is essential for the improvement of treatment outcomes. Standardization of oral health care delivery mechanisms will facilitate evaluation at national and regional levels. Oral health care workers have a moral obligation to participate in sustained campaigns to reduce the social stigma associated with HIV/AIDS in their work places at every stage of the referral chain. Future research also needs to realign itself towards prevention using the common risk factor approach, which has a broader impact on non-communicable diseases, which are increasingly affecting patients with HIV/AIDS as their life expectancies increase. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Will a quadruple multiplexed point-of-care screening strategy for HIV-related co-infections be feasible and impact detection of new co-infections in at-risk populations? Results from cross-sectional studies.

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Pai, Nitika Pant; Dhurat, Rachita; Potter, Martin; Behlim, Tarannum; Landry, Geneviève; Vadnais, Caroline; Rodrigues, Camilla; Joseph, Lawrence; Shetty, Anjali

2014-12-15

Multiplexed point-of-care (POC) devices can rapidly screen for HIV-related co-infections (eg, hepatitis C (HCV), hepatitis B (HBV), syphilis) in one patient visit, but global evidence for this approach remains limited. This study aimed to evaluate a multiplex POC testing strategy to expedite screening for HIV-related co-infections in at-risk populations. A multiplex strategy was developed with two subsequent versions of an investigational device Miriad. It was evaluated in two non-comparable settings and populations in two countries for feasibility of conduct, detection of new infections, preference and accuracy. Version 1 was evaluated in 375 sexually transmitted disease clinic attendees in Mumbai, India; version 2 was evaluated in 119 injection drug users in Montreal, Canada. Feasibility (completion rate) of the multiplex strategy was high (86.1% Mumbai; 92.4% Montreal). A total of 170 new infections were detected in Mumbai (56 HIV, 75 HBV, 37 syphilis, 2 HCV) versus 2 in Montreal. Preference was 60% in Mumbai and 97% in Montreal. Miriad version 1 specificities were high: HIV 99.7% (98.3% to 100%), HBV 99.3% (97.6% to 99.9%), HCV 99.7% (98.5% to 99.9%), syphilis 85.2% (80.9% to 88.8%); sensitivities were as follows: HIV 100% (94.8% to 100%), HBV 13.3% (6.6% to 23.2%), HCV 50% (1.3% to 98.7%), syphilis 86.1% (70.5% to 95.3%). With version 2, specificities improved: HIV 100% (97.2% to 100%), HBV 100% (97.3% to 100%), HCV 85.3% (73.8% to 93.0%), syphilis 98.1% (93.3% to 99.8%); sensitivities were: HIV 100% (47.3% to 100%), HCV 80.4% (66.1% to 90.6%), syphilis 100% (22.4% to 100%). A quad multiplex POC strategy for HIV and co-infections was feasible to operationalise and preferred by patients in both settings. Many new infections were identified in Mumbai and accuracy improved with version 2 of the assay. Such a strategy will help expedite screening for co-infections, particularly where baseline screening is low. These findings are valuable to practitioners

Recent progress in immune-based interventions to prevent HIV-1 transmission to children.

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Voronin, Yegor; Jani, Ilesh; Graham, Barney S; Cunningham, Coleen K; Mofenson, Lynne M; Musoke, Philippa M; Permar, Sallie R; Scarlatti, Gabriella

2017-12-01

Globally, 150,000 new paediatric human immunodeficiency virus type 1 (HIV-1) infections occurred in 2015. There remain complex challenges to the global elimination of paediatric HIV-1 infection. Thus, for the global community to achieve elimination of new paediatric HIV-1 infections, innovative approaches need to be explored. Immune-based approaches to prevention of mother-to-child transmission (MTCT) may help fill some of the remaining gaps and provide new opportunities to achieve an AIDS-free generation. Immune-based interventions to prevent MTCT of HIV-1 may include paediatric HIV vaccines and passive immunization approaches. Recent discoveries providing evidence of robust immune responses to HIV in infants open new and exciting prospects for paediatric HIV vaccines. Moreover, successful vaccination of infants has a different set of requirements than vaccination of adults and may be easier to achieve. Proof-of-concept has been established over the last two decades that passively administered HIV-1 Env-specific monoclonal antibody (mAbs) can prevent chimeric simian human immunodeficiency virus (SHIV) transmission to newborn nonhuman primates. There has been tremendous progress in isolating and characterizing broadly neutralizing antibodies to HIV, and clinical testing of these antibodies for treatment and prevention in both infants and adults is a major effort in the field. Immune-based interventions need to be actively explored as they can provide critically important tools to address persistent challenges in MTCT prevention. It is a pivotal time for the field with active discussions on the best strategy to further reduce HIV infection of infants and accomplish the World Health Organization Fast-Track 2030 goals to eliminate new paediatric HIV infections. © 2017 The Authors. Journal of the International AIDS Society published by John Wiley & sons Ltd on behalf of the International AIDS Society.

Tandem bispecific neutralizing antibody eliminates HIV-1 infection in humanized mice.

Science.gov (United States)

Wu, Xilin; Guo, Jia; Niu, Mengyue; An, Minghui; Liu, Li; Wang, Hui; Jin, Xia; Zhang, Qi; Lam, Ka Shing; Wu, Tongjin; Wang, Hua; Wang, Qian; Du, Yanhua; Li, Jingjing; Cheng, Lin; Tang, Hang Ying; Shang, Hong; Zhang, Linqi; Zhou, Paul; Chen, Zhiwei

2018-04-23

The discovery of an HIV-1 cure remains a medical challenge because the virus rebounds quickly after the cessation of combination antiretroviral therapy (cART). Here, we investigate the potential of an engineered tandem bispecific broadly neutralizing antibody (bs-bnAb) as an innovative product for HIV-1 prophylactic and therapeutic interventions. We discovered that by preserving 2 single-chain variable fragment (scFv) binding domains of each parental bnAb, a single gene-encoded tandem bs-bnAb, BiIA-SG, displayed substantially improved breadth and potency. BiIA-SG neutralized all 124 HIV-1-pseudotyped viruses tested, including global subtypes/recombinant forms, transmitted/founder viruses, variants not susceptible to parental bnAbs and to many other bnAbs with an average IC50 value of 0.073 μg/ml (range HIV-1 stains. Moreover, whereas BiIA-SG delayed viral rebound in a short-term therapeutic setting when combined with cART, a single injection of adeno-associated virus-transferred (AAV-transferred) BiIA-SG gene resulted dose-dependently in prolonged in vivo expression of BiIA-SG, which was associated with complete viremia control and subsequent elimination of infected cells in humanized mice. These results warrant the clinical development of BiIA-SG as a promising bs-bnAb-based biomedical intervention for the prevention and treatment of HIV-1 infection.

Barriers to access prevention of mother-to-child transmission for HIV positive women in a well-resourced setting in Vietnam

NARCIS (Netherlands)

Nguyen, T.A.; Oosterhoff, P.P.J.; Yen, P.N.; Wright, P.; Hardon, A.P.

2008-01-01

Background: According to Vietnamese policy, HIV-infected women should have access at least to HIV testing and Nevirapine prophylaxis, or where available, to adequate counselling, HIV infection staging, ARV prophylaxis, and infant formula. Many studies in high HIV prevalence settings have reported

HIV rapid testing in a Veterans Affairs hospital ED setting: a 5-year sustainability evaluation.

Science.gov (United States)

Knapp, Herschel; Hagedorn, Hildi; Anaya, Henry D

2014-08-01

Routine HIV testing in primary care settings is now recommended in the United States. The US Department of Veterans Affairs (VA) has increased the number of patients tested for HIV, but overall HIV testing rates in VA remain low. A proven strategy for increasing such testing involves nurse-initiated HIV rapid testing (HIV RT). The purpose of this work was to use a mixed methodology approach to evaluate the 5-year sustainability of an intervention that implemented HIV RT in a VA emergency department setting in a large, urban VA medical center to reduce missed diagnostic and treatment opportunities in this vulnerable patient population. In-person semistructured interviews were conducted with providers and stakeholders. Interview notes were qualitatively coded for emerging themes. Quarterly testing rates were evaluated for a 5-year time span starting from the launch in July 2008. Findings indicate that HIV RT was sustained by the enthusiasm of 2 clinical champions who oversaw the registered nurses responsible for conducting the testing. The departure of the clinical champions was correlated with a substantial drop-off in testing. Findings also indicate potential strategies for improving sustainability including engaging senior leadership in the project, engaging line staff in the implementation planning from the start to increase ownership over the innovation, incorporating information into initial training explaining the importance of the innovation to quality patient care, providing ongoing training to maintain skills, and providing routine progress reports to staff to demonstrate the ongoing impact of their efforts. Published by Elsevier Inc.

DBR1 siRNA inhibition of HIV-1 replication

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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.

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

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.

What's new? Investigating risk factors for severe childhood malnutrition in a high HIV prevalence South African setting.

Science.gov (United States)

Saloojee, Haroon; De Maayer, Tim; Garenne, Michel L; Kahn, Kathleen

2007-08-01

To identify risk factors for severe childhood malnutrition in a rural South African district with a high HIV/AIDS prevalence. Case-control study. Bushbuckridge District, Limpopo Province, South Africa. 100 children with severe malnutrition (marasmus, kwashiorkor, and marasmic kwashiorkor) were compared with 200 better nourished (>-2 SD weight-for-age) controls, matched by age and village of residence. Bivariate and multivariate analyses were conducted on a variety of biological and social risk factors. HIV status was known only for a minority of cases (39%), of whom 87% were HIV positive, while 45% of controls were stunted. In multivariate analysis, risk factors for severe malnutrition included suspicion of HIV in the family (parents or children) (OR 217.7, 95% CI 22.7-2091.3), poor weaning practices (OR 3.0, 95% CI 2.0-4.6), parental death (OR 38.0, 95% CI 3.8-385.3), male sex (OR 2.7, 95% CI 1.2-6.0), and higher birth order (third child or higher) (OR 2.3, 95% CI 1.0-5.1). Protective factors included a diverse food intake (OR 0.53, 95% CI 0.41-0.67) and receipt of a state child support grant (OR 0.44, 95% CI 0.20-0.97). A borderline association existed for family wealth (OR 0.9 per unit, 95% CI 0.83-1.0), father smoking marijuana (OR 3.9, 95% CI 1.1-14.5), and history of a pulmonary tuberculosis contact (OR 3.2, 95% CI 0.9-11.0). Despite the increasing contribution of HIV to the development of severe malnutrition, traditional risk factors such as poor nutrition, parental disadvantage and illness, poverty, and social inequity remain important contributors to the prevalence of severe malnutrition. Interventions aiming to prevent and reduce severe childhood malnutrition in high HIV prevalence settings need to encompass the various dimensions of the disease: nutritional, economic, and social, and address the prevention and treatment of HIV/AIDS.

The transcriptome of HIV-1 infected intestinal CD4+ T cells exposed to enteric bacteria.

Directory of Open Access Journals (Sweden)

Alyson C Yoder

2017-02-01

Full Text Available Global transcriptome studies can help pinpoint key cellular pathways exploited by viruses to replicate and cause pathogenesis. Previous data showed that laboratory-adapted HIV-1 triggers significant gene expression changes in CD4+ T cell lines and mitogen-activated CD4+ T cells from peripheral blood. However, HIV-1 primarily targets mucosal compartments during acute infection in vivo. Moreover, early HIV-1 infection causes extensive depletion of CD4+ T cells in the gastrointestinal tract that herald persistent inflammation due to the translocation of enteric microbes to the systemic circulation. Here, we profiled the transcriptome of primary intestinal CD4+ T cells infected ex vivo with transmitted/founder (TF HIV-1. Infections were performed in the presence or absence of Prevotella stercorea, a gut microbe enriched in the mucosa of HIV-1-infected individuals that enhanced both TF HIV-1 replication and CD4+ T cell death ex vivo. In the absence of bacteria, HIV-1 triggered a cellular shutdown response involving the downregulation of HIV-1 reactome genes, while perturbing genes linked to OX40, PPAR and FOXO3 signaling. However, in the presence of bacteria, HIV-1 did not perturb these gene sets or pathways. Instead, HIV-1 enhanced granzyme expression and Th17 cell function, inhibited G1/S cell cycle checkpoint genes and triggered downstream cell death pathways in microbe-exposed gut CD4+ T cells. To gain insights on these differential effects, we profiled the gene expression landscape of HIV-1-uninfected gut CD4+ T cells exposed to bacteria. Microbial exposure upregulated genes involved in cellular proliferation, MAPK activation, Th17 cell differentiation and type I interferon signaling. Our findings reveal that microbial exposure influenced how HIV-1 altered the gut CD4+ T cell transcriptome, with potential consequences for HIV-1 susceptibility, cell survival and inflammation. The HIV-1- and microbe-altered pathways unraveled here may serve as a

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

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.

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.

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.

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

Robust non-rigid point set registration using student's-t mixture model.

Directory of Open Access Journals (Sweden)

Zhiyong Zhou

Full Text Available The Student's-t mixture model, which is heavily tailed and more robust than the Gaussian mixture model, has recently received great attention on image processing. In this paper, we propose a robust non-rigid point set registration algorithm using the Student's-t mixture model. Specifically, first, we consider the alignment of two point sets as a probability density estimation problem and treat one point set as Student's-t mixture model centroids. Then, we fit the Student's-t mixture model centroids to the other point set which is treated as data. Finally, we get the closed-form solutions of registration parameters, leading to a computationally efficient registration algorithm. The proposed algorithm is especially effective for addressing the non-rigid point set registration problem when significant amounts of noise and outliers are present. Moreover, less registration parameters have to be set manually for our algorithm compared to the popular coherent points drift (CPD algorithm. We have compared our algorithm with other state-of-the-art registration algorithms on both 2D and 3D data with noise and outliers, where our non-rigid registration algorithm showed accurate results and outperformed the other algorithms.

“Computerized Counseling Reduces HIV-1 Viral Load and Sexual Transmission Risk: Findings from a Randomized Controlled Trial”

Science.gov (United States)

KURTH, Ann E.; SPIELBERG, Freya; CLELAND, Charles M.; LAMBDIN, Barrot; BANGSBERG, David R.; FRICK, Pamela A.; SEVERYNEN, Anneleen O.; CLAUSEN, Marc; NORMAN, Robert G.; LOCKHART, David; SIMONI, Jane M.; HOLMES, King K.

2014-01-01

Objective Evaluate a computerized intervention supporting antiretroviral therapy (ART) adherence and HIV transmission prevention. Design Longitudinal RCT. Settings An academic HIV clinic and a community-based organization in Seattle. Subjects 240 HIV-positive adults on ART; 209 completed nine-month follow-up (87% retention). Intervention Randomization to computerized counseling or assessment-only, 4 sessions over 9 months. Main Outcome Measures HIV-1 viral suppression, and self-reported ART adherence, and transmission risks, compared using generalized estimating equations. Results Overall, intervention participants had reduced viral load (VL): mean 0.17 log10 decline, versus 0.13 increase in controls, p = 0.053, and significant difference in ART adherence baseline to 9 months (p = 0.046). Their sexual transmission risk behaviors decreased (OR = 0.55, p = 0.020), a reduction not seen among controls (OR = 1.1, p = 0.664), and a significant difference in change (p = 0.040). Intervention effect was driven by those most in need: among those with detectable virus at baseline (>30 copies/milliliter, n=89), intervention effect was mean 0.60 log10 VL decline versus 0.15 increase in controls, p=0.034. ART adherence at the final follow-up was 13 points higher among intervention participants versus controls, p = 0.038. Conclusions Computerized counseling is promising for integrated ART adherence and safer sex, especially for individuals with problems in these areas. This is the first intervention to report improved ART adherence, viral suppression, and reduced secondary sexual transmission risk behavior. PMID:24384803

Proteomic Profiling of a Primary CD4+ T Cell Model of HIV-1 Latency Identifies Proteins Whose Differential Expression Correlates with Reactivation of Latent HIV-1.

Science.gov (United States)

Saha, Jamaluddin Md; Liu, Hongbing; Hu, Pei-Wen; Nikolai, Bryan C; Wu, Hulin; Miao, Hongyu; Rice, Andrew P

2018-01-01

The latent HIV-1 reservoir of memory CD4 + T cells that persists during combination antiviral therapy prevents a cure of infection. Insight into mechanisms of latency and viral reactivation are essential for the rational design of strategies to reduce the latent reservoir. In this study, we quantified the levels of >2,600 proteins in the CCL19 primary CD4 + T cell model of HIV-1 latency. We profiled proteins under conditions that promote latent infection and after cells were treated with phorbol 12-myristate 13-acetate (PMA) + ionomycin, which is known to efficiently induce reactivation of latent HIV-1. In an analysis of cells from two healthy blood donors, we identified 61 proteins that were upregulated ≥2-fold, and 36 proteins that were downregulated ≥2-fold under conditions in which latent viruses were reactivated. These differentially expressed proteins are, therefore, candidates for cellular factors that regulate latency or viral reactivation. Two unexpected findings were obtained from the proteomic data: (1) the interactions among the majority of upregulated proteins are largely undetermined in published protein-protein interaction networks and (2) downregulated proteins are strongly associated with Gene Ontology terms related to mitochondrial protein synthesis. This proteomic data set provides a useful resource for future mechanistic studies of HIV-1 latency.

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

Directory of Open Access Journals (Sweden)

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.

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.

Clonal expansion of genome-intact HIV-1 in functionally polarized Th1 CD4+ T cells.

Science.gov (United States)

Lee, Guinevere Q; Orlova-Fink, Nina; Einkauf, Kevin; Chowdhury, Fatema Z; Sun, Xiaoming; Harrington, Sean; Kuo, Hsiao-Hsuan; Hua, Stephane; Chen, Hsiao-Rong; Ouyang, Zhengyu; Reddy, Kavidha; Dong, Krista; Ndung'u, Thumbi; Walker, Bruce D; Rosenberg, Eric S; Yu, Xu G; Lichterfeld, Mathias

2017-06-30

HIV-1 causes a chronic, incurable disease due to its persistence in CD4+ T cells that contain replication-competent provirus, but exhibit little or no active viral gene expression and effectively resist combination antiretroviral therapy (cART). These latently infected T cells represent an extremely small proportion of all circulating CD4+ T cells but possess a remarkable long-term stability and typically persist throughout life, for reasons that are not fully understood. Here we performed massive single-genome, near-full-length next-generation sequencing of HIV-1 DNA derived from unfractionated peripheral blood mononuclear cells, ex vivo-isolated CD4+ T cells, and subsets of functionally polarized memory CD4+ T cells. This approach identified multiple sets of independent, near-full-length proviral sequences from cART-treated individuals that were completely identical, consistent with clonal expansion of CD4+ T cells harboring intact HIV-1. Intact, near-full-genome HIV-1 DNA sequences that were derived from such clonally expanded CD4+ T cells constituted 62% of all analyzed genome-intact sequences in memory CD4 T cells, were preferentially observed in Th1-polarized cells, were longitudinally detected over a duration of up to 5 years, and were fully replication- and infection-competent. Together, these data suggest that clonal proliferation of Th1-polarized CD4+ T cells encoding for intact HIV-1 represents a driving force for stabilizing the pool of latently infected CD4+ T cells.

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...

Quantitative analysis of differentially expressed saliva proteins in human immunodeficiency virus type 1 (HIV-1) infected individuals

International Nuclear Information System (INIS)

Zhang, Nawei; Zhang, Zhenyu; Feng, Shan; Wang, Qingtao; Malamud, Daniel; Deng, Haiteng

2013-01-01

Highlights: ► A high-throughput method for profiling and quantification of the differentially expressed proteins in saliva samples was developed. ► Identified that DMBT1, S100A7, S100A8, S100A9 and alpha defensin were up-regulated in saliva from HIV-1 seropositive patients. ► Established analytical strategies are translatable to the clinical setting. -- Abstract: In the present study, we have established a new methodology to analyze saliva proteins from HIV-1-seropositive patients before highly active antiretroviral therapy (HAART) and seronegative controls. A total of 593 and 601 proteins were identified in the pooled saliva samples from 5 HIV-1 subjects and 5 controls, respectively. Forty-one proteins were found to be differentially expressed. Bioinformatic analysis of differentially expressed salivary proteins showed an increase of antimicrobial proteins and decrease of protease inhibitors upon HIV-1 infection. To validate some of these differentially expressed proteins, a high-throughput quantitation method was established to determine concentrations of 10 salivary proteins in 40 individual saliva samples from 20 seropositive patients before HAART and 20 seronegative subjects. This method was based on limited protein separation within the zone of the stacking gel of the 1D SDS PAGE and using isotope-coded synthetic peptides as internal standards. The results demonstrated that a combination of protein profiling and targeted quantitation is an efficient method to identify and validate differentially expressed salivary proteins. Expression levels of members of the calcium-binding S100 protein family and deleted in malignant brain tumors 1 protein (DMBT1) were up-regulated while that of Mucin 5B was down-regulated in HIV-1 seropositive saliva samples, which may provide new perspectives for monitoring HIV-infection and understanding the mechanism of HIV-1 infectivity

Quantitative analysis of differentially expressed saliva proteins in human immunodeficiency virus type 1 (HIV-1) infected individuals

Energy Technology Data Exchange (ETDEWEB)

Zhang, Nawei; Zhang, Zhenyu [Beijing Chaoyang Hospital Affiliated Capital Medical University, Beijing (China); Feng, Shan [MOE Key Laboratory of Bioinformatics, School of Life Sciences, Tsinghua University, Beijing (China); Wang, Qingtao [Beijing Chaoyang Hospital Affiliated Capital Medical University, Beijing (China); Malamud, Daniel [NYU College of Dentistry, 345 East 24th Street, New York, NY 10010 (United States); Deng, Haiteng, E-mail: dht@mail.tsinghua.edu.cn [MOE Key Laboratory of Bioinformatics, School of Life Sciences, Tsinghua University, Beijing (China)

2013-04-24

Highlights: ► A high-throughput method for profiling and quantification of the differentially expressed proteins in saliva samples was developed. ► Identified that DMBT1, S100A7, S100A8, S100A9 and alpha defensin were up-regulated in saliva from HIV-1 seropositive patients. ► Established analytical strategies are translatable to the clinical setting. -- Abstract: In the present study, we have established a new methodology to analyze saliva proteins from HIV-1-seropositive patients before highly active antiretroviral therapy (HAART) and seronegative controls. A total of 593 and 601 proteins were identified in the pooled saliva samples from 5 HIV-1 subjects and 5 controls, respectively. Forty-one proteins were found to be differentially expressed. Bioinformatic analysis of differentially expressed salivary proteins showed an increase of antimicrobial proteins and decrease of protease inhibitors upon HIV-1 infection. To validate some of these differentially expressed proteins, a high-throughput quantitation method was established to determine concentrations of 10 salivary proteins in 40 individual saliva samples from 20 seropositive patients before HAART and 20 seronegative subjects. This method was based on limited protein separation within the zone of the stacking gel of the 1D SDS PAGE and using isotope-coded synthetic peptides as internal standards. The results demonstrated that a combination of protein profiling and targeted quantitation is an efficient method to identify and validate differentially expressed salivary proteins. Expression levels of members of the calcium-binding S100 protein family and deleted in malignant brain tumors 1 protein (DMBT1) were up-regulated while that of Mucin 5B was down-regulated in HIV-1 seropositive saliva samples, which may provide new perspectives for monitoring HIV-infection and understanding the mechanism of HIV-1 infectivity.

Dolutegravir plus abacavir-lamivudine for the treatment of HIV-1 infection.

Science.gov (United States)

Walmsley, Sharon L; Antela, Antonio; Clumeck, Nathan; Duiculescu, Dan; Eberhard, Andrea; Gutiérrez, Felix; Hocqueloux, Laurent; Maggiolo, Franco; Sandkovsky, Uriel; Granier, Catherine; Pappa, Keith; Wynne, Brian; Min, Sherene; Nichols, Garrett

2013-11-07

Dolutegravir (S/GSK1349572), a once-daily, unboosted integrase inhibitor, was recently approved in the United States for the treatment of human immunodeficiency virus type 1 (HIV-1) infection in combination with other antiretroviral agents. Dolutegravir, in combination with abacavir-lamivudine, may provide a simplified regimen. We conducted a randomized, double-blind, phase 3 study involving adult participants who had not received previous therapy for HIV-1 infection and who had an HIV-1 RNA level of 1000 copies per milliliter or more. Participants were randomly assigned to dolutegravir at a dose of 50 mg plus abacavir-lamivudine once daily (DTG-ABC-3TC group) or combination therapy with efavirenz-tenofovir disoproxil fumarate (DF)-emtricitabine once daily (EFV-TDF-FTC group). The primary end point was the proportion of participants with an HIV-1 RNA level of less than 50 copies per milliliter at week 48. Secondary end points included the time to viral suppression, the change from baseline in CD4+ T-cell count, safety, and viral resistance. A total of 833 participants received at least one dose of study drug. At week 48, the proportion of participants with an HIV-1 RNA level of less than 50 copies per milliliter was significantly higher in the DTG-ABC-3TC group than in the EFV-TDF-FTC group (88% vs. 81%, P=0.003), thus meeting the criterion for superiority. The DTG-ABC-3TC group had a shorter median time to viral suppression than did the EFV-TDF-FTC group (28 vs. 84 days, Pdreams, anxiety, dizziness, and somnolence) were significantly more common in the EFV-TDF-FTC group, whereas insomnia was reported more frequently in the DTG-ABC-3TC group. No participants in the DTG-ABC-3TC group had detectable antiviral resistance; one tenofovir DF-associated mutation and four efavirenz-associated mutations were detected in participants with virologic failure in the EFV-TDF-FTC group. Dolutegravir plus abacavir-lamivudine had a better safety profile and was more effective

Optimal Set-Point Synthesis in HVAC Systems

DEFF Research Database (Denmark)

Komareji, Mohammad; Stoustrup, Jakob; Rasmussen, Henrik

2007-01-01

This paper presents optimal set-point synthesis for a heating, ventilating, and air-conditioning (HVAC) system. This HVAC system is made of two heat exchangers: an air-to-air heat exchanger and a water-to-air heat exchanger. The objective function is composed of the electrical power for different...... components, encompassing fans, primary/secondary pump, tertiary pump, and air-to-air heat exchanger wheel; and a fraction of thermal power used by the HVAC system. The goals that have to be achieved by the HVAC system appear as constraints in the optimization problem. To solve the optimization problem......, a steady state model of the HVAC system is derived while different supplying hydronic circuits are studied for the water-to-air heat exchanger. Finally, the optimal set-points and the optimal supplying hydronic circuit are resulted....

Geometric Spanners for Weighted Point Sets

DEFF Research Database (Denmark)

Abam, Mohammad; de Berg, Mark; Farshi, Mohammad

2009-01-01

Let (S,d) be a finite metric space, where each element p ∈ S has a non-negative weight w(p). We study spanners for the set S with respect to weighted distance function d w , where d w (p,q) is w(p) + d(p,q) + wq if p ≠ q and 0 otherwise. We present a general method for turning spanners with respect...... to the d-metric into spanners with respect to the d w -metric. For any given ε> 0, we can apply our method to obtain (5 + ε)-spanners with a linear number of edges for three cases: points in Euclidean space ℝ d , points in spaces of bounded doubling dimension, and points on the boundary of a convex body...... in ℝ d where d is the geodesic distance function. We also describe an alternative method that leads to (2 + ε)-spanners for points in ℝ d and for points on the boundary of a convex body in ℝ d . The number of edges in these spanners is O(nlogn). This bound on the stretch factor is nearly optimal...

Priority setting in HIV/AIDS control in West Java Indonesia: an evaluation based on the accountability for reasonableness framework.

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Tromp, Noor; Prawiranegara, Rozar; Subhan Riparev, Harris; Siregar, Adiatma; Sunjaya, Deni; Baltussen, Rob

2015-04-01

Indonesia has insufficient resources to adequately respond to the HIV/AIDS epidemic, and thus faces a great challenge in prioritizing interventions. In many countries, such priority setting processes are typically ad hoc and not transparent leading to unfair decisions. Here, we evaluated the priority setting process in HIV/AIDS control in West Java province against the four conditions of the accountability for reasonableness (A4R) framework: relevance, publicity, appeals and revision, and enforcement. We reviewed government documents and conducted semi-structured qualitative interviews based on the A4R framework with 22 participants of the 5-year HIV/AIDS strategy development for 2008-13 (West Java province) and 2007-11 (Bandung). We found that criteria for priority setting were used implicitly and that the strategies included a wide range of programmes. Many stakeholders were involved in the process but their contribution could be improved and particularly the public and people living with HIV/AIDS could be better engaged. The use of appeal and publicity mechanisms could be more transparent and formally stated. Public regulations are not yet installed to ensure fair priority setting. To increase fairness in HIV/AIDS priority setting, West Java should make improvements on all four conditions of the A4R framework. Published by Oxford University Press in association with The London School of Hygiene and Tropical Medicine © The Author 2014; all rights reserved.

Positron emission tomography in patients suffering from HIV-1 infection

Energy Technology Data Exchange (ETDEWEB)

Sathekge, Mike [University Hospital of Pretoria, Department of Nuclear Medicine, Pretoria (South Africa); Goethals, Ingeborg; Wiele, Christophe van de [University Hospital Ghent, Department of Nuclear Medicine, Ghent (Belgium); Maes, Alex [AZ Groening, Department of Nuclear Medicine, Kortrijk (Belgium)

2009-07-15

This paper reviews currently available PET studies performed either to improve our understanding of the pathogenesis of HIV-1 infection or to assess the value of PET imaging in the clinical decision making of patients infected with HIV-1 presenting with AIDS-related opportunistic infections and malignancies. FDG PET has shown that HIV-1 infection progresses by distinct anatomical steps, with involvement of the upper torso preceding involvement of the lower part of the torso, and that the degree of FDG uptake relates to viral load. The former finding suggests that lymphoid tissues are engaged in a predictable sequence and that diffusible mediators of activation might be important targets for vaccine or therapeutic intervention strategies. In lipodystrophic HIV-infected patients, limited available data support the hypothesis that stavudine-related lipodystrophy is associated with increased glucose uptake by adipose tissue as a result of the metabolic stress of adipose tissue in response to highly active antiretroviral treatment (HAART). Finally, in early AIDS-related dementia complex (ADC), striatal hypermetabolism is observed, whereas progressive ADC is characterized by a decrease in subcortical and cortical metabolism. In the clinical setting, PET has been shown to allow the differentiation of AIDS-related opportunistic infections and malignancies, and to allow monitoring of side effects of HAART. However, in patients suffering from HIV infection and presenting with extracerebral lymphoma or other human malignancies, knowledge of viraemia is essential when interpreting FDG PET imaging. (orig.)

Positron emission tomography in patients suffering from HIV-1 infection

International Nuclear Information System (INIS)

Sathekge, Mike; Goethals, Ingeborg; Wiele, Christophe van de; Maes, Alex

2009-01-01

This paper reviews currently available PET studies performed either to improve our understanding of the pathogenesis of HIV-1 infection or to assess the value of PET imaging in the clinical decision making of patients infected with HIV-1 presenting with AIDS-related opportunistic infections and malignancies. FDG PET has shown that HIV-1 infection progresses by distinct anatomical steps, with involvement of the upper torso preceding involvement of the lower part of the torso, and that the degree of FDG uptake relates to viral load. The former finding suggests that lymphoid tissues are engaged in a predictable sequence and that diffusible mediators of activation might be important targets for vaccine or therapeutic intervention strategies. In lipodystrophic HIV-infected patients, limited available data support the hypothesis that stavudine-related lipodystrophy is associated with increased glucose uptake by adipose tissue as a result of the metabolic stress of adipose tissue in response to highly active antiretroviral treatment (HAART). Finally, in early AIDS-related dementia complex (ADC), striatal hypermetabolism is observed, whereas progressive ADC is characterized by a decrease in subcortical and cortical metabolism. In the clinical setting, PET has been shown to allow the differentiation of AIDS-related opportunistic infections and malignancies, and to allow monitoring of side effects of HAART. However, in patients suffering from HIV infection and presenting with extracerebral lymphoma or other human malignancies, knowledge of viraemia is essential when interpreting FDG PET imaging. (orig.)

A Gap in Time: Extending our Knowledge of Temporal Processing Deficits in the HIV-1 Transgenic Rat.

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McLaurin, Kristen A; Moran, Landhing M; Li, Hailong; Booze, Rosemarie M; Mactutus, Charles F

2017-03-01

Approximately 50 % of HIV-1 seropositive individuals develop HIV-1 associated neurocognitive disorders (HAND), which commonly include alterations in executive functions, such as inhibition, set shifting, and complex problem solving. Executive function deficits in HIV-1 are fairly well characterized, however, relatively few studies have explored the elemental dimensions of neurocognitive impairment in HIV-1. Deficits in temporal processing, caused by HIV-1, may underlie the symptoms of impairment in higher level cognitive processes. Translational measures of temporal processing, including cross-modal prepulse inhibition (PPI), gap-prepulse inhibition (gap-PPI), and gap threshold detection, were studied in mature (ovariectomized) female HIV-1 transgenic (Tg) rats, which express 7 of the 9 HIV-1 genes constitutively throughout development. Cross-modal PPI revealed a relative insensitivity to the manipulation of interstimulus interval (ISI) in HIV-1 Tg animals in comparison to control animals, extending previously reported temporal processing deficits in HIV-1 Tg rats to a more advanced age, suggesting the permanence of temporal processing deficits. In gap-PPI, HIV-1 Tg animals exhibited a relative insensitivity to the manipulation of ISI in comparison to control animals. In gap-threshold detection, HIV-1 Tg animals displayed a profound differential sensitivity to the manipulation of gap duration. Presence of the HIV-1 transgene was diagnosed with 91.1 % accuracy using gap threshold detection measures. Understanding the generality and permanence of temporal processing deficits in the HIV-1 Tg rat is vital to modeling neurocognitive deficits observed in HAND and provides a key target for the development of a diagnostic screening tool.

Controle de polidrâmnio recorrente em gestante portadora do HIV-1: relato de caso Recurrent polyhydramnios management in an HIV-1 infected pregnant woman: a case report

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Geraldo Duarte

2004-04-01

fluid. The patient started preterm labor with 30 weeks and 5 days resulting in vaginal delivery of a male neonate weighing 1,690g and measuring 43cm. The baby presented a post natal diagnosis of a sodium-losing nephropathy and was submitted to three negative polymerase chain reaction tests for HIV-1. The authors point out that the option to manage cases of HIV-1 infected pregnancies that could need invasive obstetric procedures should be to give the patient 2 mg//kg of ZDV endovenously before the procedure, in order to avoid MTCT of HIV-1, as it has demonstrated good results in this case.

HIV-1 drug resistance in recently HIV-infected pregnant mother's naïve to antiretroviral therapy in Dodoma urban, Tanzania.

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Vairo, Francesco; Nicastri, Emanuele; Liuzzi, Giuseppina; Chaula, Zainab; Nguhuni, Boniface; Bevilacqua, Nazario; Forbici, Federica; Amendola, Alessandra; Fabeni, Lavinia; De Nardo, Pasquale; Perno, Carlo Federico; Cannas, Angela; Sakhoo, Calistus; Capobianchi, Maria Rosaria; Ippolito, Giuseppe

2013-09-21

HIV resistance affects virological response to therapy and efficacy of prophylaxis in mother-to-child-transmission. The study aims to assess the prevalence of HIV primary resistance in pregnant women naïve to antiretrovirals. Cross sectional baseline analysis of a cohort of HIV + pregnant women (HPW) enrolled in the study entitled Antiretroviral Management of Antenatal and Natal HIV Infection (AMANI, peace in Kiswahili language). The AMANI study began in May 2010 in Dodoma, Tanzania. In this observational cohort, antiretroviral treatment was provided to all women from the 28th week of gestation until the end of the breastfeeding period. Baseline CD4 cell count, viral load and HIV drug-resistance genotype were collected. Drug-resistance analysis was performed on 97 naïve infected-mothers. The prevalence of all primary drug resistance and primary non-nucleoside reverse-transcriptase inhibitors resistance was 11.9% and 7.5%, respectively. K103S was found in two women with no M184V detection. HIV-1 subtype A was the most commonly identified, with a high prevalence of subtype A1, followed by C, D, C/D recombinant, A/C recombinant and A/D recombinant. HIV drug- resistance mutations were detected in A1 and C subtypes. Our study reports an 11.9% prevalence rate of primary drug resistance in naïve HIV-infected pregnant women from a remote area of Tanzania. Considering that the non-nucleoside reverse-transcriptase inhibitors are part of the first-line antiretroviral regimen in Tanzania and all of Africa, resistance surveys should be prioritized in settings where antiretroviral therapy programs are scaled up.

Measuring health-related quality of life of HIV-positive adolescents in resource-constrained settings.

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Caroline Masquillier

Full Text Available BACKGROUND AND OBJECTIVES: Access to antiretroviral treatment among adolescents living with HIV (ALH is increasing. Health-related quality of life (HRQOL is relevant for monitoring the impact of the disease on both well-being and treatment outcomes. However, adequate screening tools to assess HRQOL in low-resource settings are scarce. This study aims to fill this research gap, by 1 assessing the psychometric properties and reliability of an Eastern African English version of a European HRQOL scale for adolescents (KIDSCREEN and 2 determining which version of the KIDSCREEN (52-, 27- and 10-item version is most suitable for low-resource settings. METHODS: The KIDSCREEN was translated into Eastern African English, Luganda (Uganda and Dholuo (Kenya according to standard procedures. The reconciled version was administered in 2011 to ALH aged 13-17 in Kenya (n = 283 and Uganda (n = 299. All three KIDSCREEN versions were fitted to the data with confirmatory factor analysis (CFA. After comparison, the most suitable version was adapted based on the CFA outcomes utilizing the results of previous formative research. In order to develop a general HRQOL factor, a second-order measurement model was fitted to the data. RESULTS: The CFA results showed that without adjustments, the KIDSCREEN cannot be used for measuring the HRQOL of HIV-positive adolescents. After comparison, the most suitable version for low-resource settings--the 27-item version--was adapted further. The introduction of a negative wording factor was required for the Dholuo model. The Dholuo (CFI: 0.93; RMSEA: 0.039 and the Luganda model (CFI: 0.90; RMSEA: 0.052 showed a good fit. All cronbach's alphas of the factors were 0.70 or above. The alpha value of the Dholuo and Lugandan HRQOL second-order factor was respectively 0.84 and 0.87. CONCLUSIONS: The study showed that the adapted KIDSCREEN-27 is an adequate tool for measuring HRQOL in low-resource settings with high HIV prevalence.

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

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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

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

Transcriptional Reprogramming during Effector-to-Memory Transition Renders CD4+ T Cells Permissive for Latent HIV-1 Infection.

Science.gov (United States)

Shan, Liang; Deng, Kai; Gao, Hongbo; Xing, Sifei; Capoferri, Adam A; Durand, Christine M; Rabi, S Alireza; Laird, Gregory M; Kim, Michelle; Hosmane, Nina N; Yang, Hung-Chih; Zhang, Hao; Margolick, Joseph B; Li, Linghua; Cai, Weiping; Ke, Ruian; Flavell, Richard A; Siliciano, Janet D; Siliciano, Robert F

2017-10-17

The latent reservoir for HIV-1 in resting memory CD4 + T cells is the major barrier to curing HIV-1 infection. Studies of HIV-1 latency have focused on regulation of viral gene expression in cells in which latent infection is established. However, it remains unclear how infection initially becomes latent. Here we described a unique set of properties of CD4 + T cells undergoing effector-to-memory transition including temporary upregulation of CCR5 expression and rapid downregulation of cellular gene transcription. These cells allowed completion of steps in the HIV-1 life cycle through integration but suppressed HIV-1 gene transcription, thus allowing the establishment of latency. CD4 + T cells in this stage were substantially more permissive for HIV-1 latent infection than other CD4 + T cells. Establishment of latent HIV-1 infection in CD4 + T could be inhibited by viral-specific CD8 + T cells, a result with implications for elimination of latent HIV-1 infection by T cell-based vaccines. Copyright © 2017. Published by Elsevier Inc.

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

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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.

Therapeutic Efficacy of Vectored PGT121 Gene Delivery in HIV-1-Infected Humanized Mice.

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Badamchi-Zadeh, Alexander; Tartaglia, Lawrence J; Abbink, Peter; Bricault, Christine A; Liu, Po-Ting; Boyd, Michael; Kirilova, Marinela; Mercado, Noe B; Nanayakkara, Ovini S; Vrbanac, Vladimir D; Tager, Andrew M; Larocca, Rafael A; Seaman, Michael S; Barouch, Dan H

2018-04-01

Broadly neutralizing antibodies (bNAbs) are being explored for HIV-1 prevention and cure strategies. However, administration of purified bNAbs poses challenges in resource-poor settings, where the HIV-1 disease burden is greatest. In vivo vector-based production of bNAbs represents an alternative strategy. We investigated adenovirus serotype 5 (Ad5) and adeno-associated virus serotype 1 (AAV1) vectors to deliver the HIV-1-specific bNAb PGT121 in wild-type and immunocompromised C57BL/6 mice as well as in HIV-1-infected bone marrow-liver-thymus (BLT) humanized mice. Ad5.PGT121 and AAV1.PGT121 produced functional antibody in vivo Ad5.PGT121 produced PGT121 rapidly within 6 h, whereas AAV1.PGT121 produced detectable PGT121 in serum by 72 h. Serum PGT121 levels were rapidly reduced by the generation of anti-PGT121 antibodies in immunocompetent mice but were durably maintained in immunocompromised mice. In HIV-1-infected BLT humanized mice, Ad5.PGT121 resulted in a greater reduction of viral loads than did AAV1.PGT121. Ad5.PGT121 also led to more-sustained virologic control than purified PGT121 IgG. Ad5.PGT121 afforded more rapid, robust, and durable antiviral efficacy than AAV1.PGT121 and purified PGT121 IgG in HIV-1-infected humanized mice. Further evaluation of vector delivery of HIV-1 bNAbs is warranted, although approaches to prevent the generation of antiantibody responses may also be required. IMPORTANCE Broadly neutralizing antibodies (bNAbs) are being explored for HIV-1 prevention and cure strategies, but delivery of purified antibodies may prove challenging. We investigated adenovirus serotype 5 (Ad5) and adeno-associated virus serotype 1 (AAV1) vectors to deliver the HIV-1-specific bNAb PGT121. Ad5.PGT121 afforded more rapid, robust, and durable antiviral efficacy than AAV1.PGT121 and purified PGT121 IgG in HIV-1-infected humanized mice. Copyright © 2018 Badamchi-Zadeh et al.

HIV-1 Reservoir Association with Immune Activation

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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.

Impact and Cost-Effectiveness of Point-Of-Care CD4 Testing on the HIV Epidemic in South Africa.

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Alastair Heffernan

Full Text Available Rapid diagnostic tools have been shown to improve linkage of patients to care. In the context of infectious diseases, assessing the impact and cost-effectiveness of such tools at the population level, accounting for both direct and indirect effects, is key to informing adoption of these tools. Point-of-care (POC CD4 testing has been shown to be highly effective in increasing the proportion of HIV positive patients who initiate ART. We assess the impact and cost-effectiveness of introducing POC CD4 testing at the population level in South Africa in a range of care contexts, using a dynamic compartmental model of HIV transmission, calibrated to the South African HIV epidemic. We performed a meta-analysis to quantify the differences between POC and laboratory CD4 testing on the proportion linking to care following CD4 testing. Cumulative infections averted and incremental cost-effectiveness ratios (ICERs were estimated over one and three years. We estimated that POC CD4 testing introduced in the current South African care context can prevent 1.7% (95% CI: 0.4% - 4.3% of new HIV infections over 1 year. In that context, POC CD4 testing was cost-effective 99.8% of the time after 1 year with a median estimated ICER of US$4,468/DALY averted. In healthcare contexts with expanded HIV testing and improved retention in care, POC CD4 testing only became cost-effective after 3 years. The results were similar when, in addition, ART was offered irrespective of CD4 count, and CD4 testing was used for clinical assessment. Our findings suggest that even if ART is expanded to all HIV positive individuals and HIV testing efforts are increased in the near future, POC CD4 testing is a cost-effective tool, even within a short time horizon. Our study also illustrates the importance of evaluating the potential impact of such diagnostic technologies at the population level, so that indirect benefits and costs can be incorporated into estimations of cost-effectiveness.

eCD4-Ig variants that more potently neutralize HIV-1.

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Fetzer, Ina; Gardner, Matthew R; Davis-Gardner, Meredith E; Prasad, Neha R; Alfant, Barnett; Weber, Jesse A; Farzan, Michael

2018-03-28

The HIV-1 entry inhibitor eCD4-Ig is a fusion of CD4-Ig and a coreceptor-mimetic peptide. eCD4-Ig is markedly more potent than CD4-Ig, with neutralization efficiencies approaching those of HIV-1 broadly neutralizing antibodies (bNAbs). However, unlike bNAbs, eCD4-Ig neutralizes all HIV-1, HIV-2 and SIV isolates that it has been tested against, suggesting that it may be useful in clinical settings where antibody escape is a concern. Here we characterize three new eCD4-Ig variants, each with different architectures and each utilizing D1.22, a stabilized form of CD4 domain 1. These variants were 10- to 20-fold more potent than our original eCD4-Ig variant, with a construct bearing four D1.22 domains (eD1.22-HL-Ig) exhibiting the greatest potency. However, this variant mediated less efficient antibody-dependent cell-mediated cytotoxicity (ADCC) activity than eCD4-Ig itself or several other eCD4-Ig variants, including the smallest variant (eD1.22-Ig). A variant with the same architecture as original eCD4-Ig (eD1.22-D2-Ig) showed modestly higher thermal stability and best prevented promotion of infection of CCR5-positive, CD4-negative cells. All three variants, and eCD4-Ig itself, mediated more efficient shedding of the HIV-1 envelope glycoprotein gp120 than did CD4-Ig. Finally, we show that only three D1.22 mutations contributed to the potency of eD1.22-D2-Ig, and that introduction of these changes into eCD4-Ig resulted in a variant 9-fold more potent than eCD4-Ig and 2-fold more potent than eD1.22-D2-Ig. These studies will assist in developing eCD4-Ig variants with properties optimized for prophylaxis, therapy, and cure applications. IMPORTANCE HIV-1 bNAbs have properties different from antiretroviral compounds. Specifically, antibodies can enlist immune effector cells to eliminate infected cells, whereas antiretroviral compounds simply interfere with various steps in the viral lifecycle. Unfortunately, HIV-1 is adept at evading antibody recognition, limiting the

Feasibility and acceptability of point of care HIV testing in community outreach and GUM drop-in services in the North West of England: A programmatic evaluation

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Jelliman Pauline

2011-06-01

Full Text Available Abstract Background In Liverpool, injecting drug users (IDUs, men-who-have-sex-with-men (MSM and UK Africans experience a disproportionate burden of HIV, yet services do not reach out to these groups and late presentations continue. We set out to: increase testing uptake in targeted marginalized groups through a community and genitourinary medicine (GUM-based point of care testing (POCT programme; and conduct a process evaluation to examine service provider inputs and document service user perceptions of the programme. Methods Mixed quantitative, qualitative and process evaluation methods were used. Service providers were trained to use fourth generation rapid antibody/antigen HIV tests. Existing outreach services incorporated POCT into routine practice. Clients completed a semi-structured questionnaire and focus group discussions (FGDs were held with service providers. Results Between September 2009 and June 2010, 953 individuals underwent POCT (GUM: 556 [59%]; community-based sites: 397 [42%]. Participants in the community were more likely to be male (p = 0.028, older (p Conclusions Community and GUM clinic-based POCT for HIV was feasible and acceptable to clients and service providers in a low prevalence setting. It successfully reached target groups, many of whom would not have otherwise tested. We recommend POCT be considered among strategies to increase the uptake of HIV testing among groups who are currently underserved.

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

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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.

Multi-Agent Rendezvousing with a Finite Set of Candidate Rendezvous Points

NARCIS (Netherlands)

Fang, J.; Morse, A. S.; Cao, M.

2008-01-01

The discrete multi-agent rendezvous problem we consider in this paper is concerned with a specified set of points in the plane, called “dwell-points,” and a set of mobile autonomous agents with limited sensing range. Each agent is initially positioned at some dwell-point, and is able to determine

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

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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

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

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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

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

Contribution of immunological and virological factors to extremely severe primary HIV-1 infection

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Dalmau, Judith; Puertas, Maria Carmen; Azuara, Marta; Mariño, Ana; Frahm, Nicole; Mothe, Beatriz; Izquierdo-Useros, Nuria; Buzón, Maria José; Paredes, Roger; Matas, Lourdes; Allen, Todd M.; Brander, Christian; Rodrigo, Carlos; Clotet, Bonaventura; Martinez-Picado, Javier

2009-01-01

Background During acute HIV infection, high viral loads and the induction of host immune responses typically coincide with the onset of clinical symptoms. However, clinically severe presentations during acute HIV-1 infection, including AIDS-defining symptoms, are unusual. Methods Virus isolates were tested for clade, drug susceptibility, coreceptor usage, and growth rate for two cases of clinically severe sexual transmission. HLA genotype was determined, and HIV-1-specific CTL responses to an overlapping peptide set spanning the entire HIV clade A and clade B proteome were assayed. Results The virus isolated from the two unrelated cases of severe primary HIV-1 infection showed R5/X4 dual/mixed tropism, belonged to clade B and CRF02-AG, and were highly replicative in peripheral blood mononuclear cell culture. Impaired humoral responses were paralleled by a profound absence of HIV-1-specific CTL responses to the entire viral proteome in the two study cases. One case for which the virus source was available, showed a remarkable HLA similarity between the transmission pair as all 4 HLA-A and -B alleles were HLA supertype-matched between the subjects involved in the transmission case. Conclusions The data suggest that concurrence of viral and host factors contribute to the clinical severity of primary HIV-1 infection and that subjects infected with highly replicative dual tropic viruses are more prone to develop AIDS-defining symptoms during acute infection if they are unable to mount humoral and cellular HIV-1-specific immune responses. Concordant HLA supertypes might facilitate the preferential transmission of HLA-adapted viral variants, further accelerating disease progression. PMID:19093810

Definition of a core set of quality indicators for the assessment of HIV/AIDS clinical care: a systematic review

Science.gov (United States)

2013-01-01

Background Several organizations and individual authors have been proposing quality indicators for the assessment of clinical care in HIV/AIDS patients. Nevertheless, the definition of a consensual core set of indicators remains controversial and its practical use is largely limited. This study aims not only to identify and characterize these indicators through a systematic literature review but also to propose a parsimonious model based on those most used. Methods MEDLINE, SCOPUS, Cochrane databases and ISI Web of Knowledge, as well as official websites of organizations dealing with HIV/AIDS care, were searched for articles and information proposing HIV/AIDS clinical care quality indicators. The ones that are on patient’s perspective and based on services set were excluded. Data extraction, using a predefined data sheet based on Cochrane recommendations, was done by one of the authors while a second author rechecked the extracted data for any inconsistency. Results A total of 360 articles were identified in our search query but only 12 of them met the inclusion criteria. We also identified one relevant site. Overall, we identified 65 quality indicators for HIV/AIDS clinical care distributed as following: outcome (n=15) and process-related (n=50) indicators; generic (n=36) and HIV/AIDS disease-specific (n=29) indicators; baseline examinations (n=19), screening (n=9), immunization (n=4), prophylaxis (n=5), HIV monitoring (n=16), and therapy (=12) indicators. Conclusions There are several studies that set up HIV clinical care indicators, with only a part of them useful to assess the HIV clinical care. More importantly, HIV/AIDS clinical care indicators need to be valid, reliable and most of all feasible. PMID:23809537

Modelling occupants’ heating set-point prefferences

DEFF Research Database (Denmark)

Andersen, Rune Vinther; Olesen, Bjarne W.; Toftum, Jørn

2011-01-01

consumption. Simultaneous measurement of the set-point of thermostatic radiator valves (trv), and indoor and outdoor environment characteristics was carried out in 15 dwellings in Denmark in 2008. Linear regression was used to infer a model of occupants’ interactions with trvs. This model could easily...... be implemented in most simulation software packages to increase the validity of the simulation outcomes....

Independent predictors of tuberculosis mortality in a high HIV prevalence setting: a retrospective cohort study.

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Pepper, Dominique J; Schomaker, Michael; Wilkinson, Robert J; de Azevedo, Virginia; Maartens, Gary

2015-01-01

Identifying those at increased risk of death during TB treatment is a priority in resource-constrained settings. We performed this study to determine predictors of mortality during TB treatment. We performed a retrospective analysis of a TB surveillance population in a high HIV prevalence area that was recorded in ETR.net (Electronic Tuberculosis Register). Adult TB cases initiated TB treatment from 2007 through 2009 in Khayelitsha, South Africa. Cox proportional hazards models were used to identify risk factors for death (after multiple imputations for missing data). Model selection was performed using Akaike's Information Criterion to obtain the most relevant predictors of death. Of 16,209 adult TB cases, 851 (5.3 %) died during TB treatment. In all TB cases, advancing age, co-infection with HIV, a prior history of TB and the presence of both pulmonary and extra-pulmonary TB were independently associated with an increasing hazard of death. In HIV-infected TB cases, advancing age and female gender were independently associated with an increasing hazard of death. Increasing CD4 counts and antiretroviral treatment during TB treatment were protective against death. In HIV-uninfected TB cases, advancing age was independently associated with death, whereas smear-positive disease was protective. We identified several independent predictors of death during TB treatment in resource-constrained settings. Our findings inform resource-constrained settings about certain subgroups of TB patients that should be targeted to improve mortality during TB treatment.

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.

HIV-1 gp41 Fusion Intermediate: A Target for HIV Therapeutics

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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.

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

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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.

Accumulation of MxB/Mx2-resistant HIV-1 Capsid Variants During Expansion of the HIV-1 Epidemic in Human Populations.

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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.

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

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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

Variations in the Biological Functions of HIV-1 Clade C Envelope in a SHIV-Infected Rhesus Macaque during Disease Progression.

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For Yue Tso

Full Text Available A better understanding of how the biological functions of the HIV-1 envelope (Env changes during disease progression may aid the design of an efficacious anti-HIV-1 vaccine. Although studies from patient had provided some insights on this issue, the differences in the study cohorts and methodology had make it difficult to reach a consensus of the variations in the HIV-1 Env functions during disease progression. To this end, an animal model that can be infected under controlled environment and reflect the disease course of HIV-1 infection in human will be beneficial. Such an animal model was previously demonstrated by the infection of macaque with SHIV, expressing HIV-1 clade C Env V1-V5 region. By using this model, we examined the changes in biological functions of Env in the infected animal over the entire disease course. Our data showed an increase in the neutralization resistance phenotype over time and coincided with the decrease in the net charges of the V1-V5 region. Infection of PBMC with provirus expressing various Env clones, isolated from the infected animal over time, showed a surprisingly better replicative fitness for viruses expressing the Env from early time point. Biotinylation and ELISA data also indicated a decrease of cell-surface-associated Env and virion-associated gp120 content with disease progression. This decrease did not affect the CD4-binding capability of Env, but were positively correlated with the decrease of Env fusion ability. Interestingly, some of these changes in biological functions reverted to the pre-AIDS level during advance AIDS. These data suggested a dynamic relationship between the Env V1-V5 region with the host immune pressure. The observed changes of biological functions in this setting might reflect and predict those occurring during natural disease progression in human.

Human nucleoporins promote HIV-1 docking at the nuclear pore, nuclear import and integration.

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Francesca Di Nunzio

Full Text Available The nuclear pore complex (NPC mediates nucleo-cytoplasmic transport of macromolecules and is an obligatory point of passage and functional bottleneck in the replication of some viruses. The Human Immunodeficiency Virus (HIV has evolved the required mechanisms for active nuclear import of its genome through the NPC. However the mechanisms by which the NPC allows or even assists HIV translocation are still unknown. We investigated the involvement of four key nucleoporins in HIV-1 docking, translocation, and integration: Nup358/RanBP2, Nup214/CAN, Nup98 and Nup153. Although all induce defects in infectivity when depleted, only Nup153 actually showed any evidence of participating in HIV-1 translocation through the nuclear pore. We show that Nup358/RanBP2 mediates docking of HIV-1 cores on NPC cytoplasmic filaments by interacting with the cores and that the C-terminus of Nup358/RanBP2 comprising a cyclophilin-homology domain contributes to binding. We also show that Nup214/CAN and Nup98 play no role in HIV-1 nuclear import per se: Nup214/CAN plays an indirect role in infectivity read-outs through its effect on mRNA export, while the reduction of expression of Nup98 shows a slight reduction in proviral integration. Our work shows the involvement of nucleoporins in diverse and functionally separable steps of HIV infection and nuclear import.

Tandem bispecific broadly neutralizing antibody - a novel approach to HIV-1 treatment.

Science.gov (United States)

Ferrari, Guido

2018-04-23

The last decade has led to a significant advance in our knowledge of HIV-1 latency and immunity. However, we are still not close to finding a cure for HIV-1. Although combination antiretroviral therapy (cART) has led to increased survival, almost close to that of the general population, it is still not curative. In the current issue of the JCI, Wu et al. studied the prophylactic and therapeutic potential of an engineered tandem bispecific broadly neutralizing antibody (bs-bnAb), BiIA-SG. This bnAb's breadth and potency were highly effective in protection and treatment settings, as measured by complete viremia control following direct infusion, as well as elimination of infected cells and delay in viral rebound when delivered with a recombinant vector. These observations underscore the need for the clinical development of BiIA-SG for the prevention of HIV-1.

[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.

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...

Relationship of HIV Reservoir Characteristics with Immune Status and Viral Rebound Kinetics in an HIV Therapeutic Vaccine Study