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  1. HLA Class-II Associated HIV Polymorphisms Predict Escape from CD4+ T Cell Responses.

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    Nathan Erdmann

    2015-08-01

    Full Text Available Antiretroviral therapy, antibody and CD8+ T cell-mediated responses targeting human immunodeficiency virus-1 (HIV-1 exert selection pressure on the virus necessitating escape; however, the ability of CD4+ T cells to exert selective pressure remains unclear. Using a computational approach on HIV gag/pol/nef sequences and HLA-II allelic data, we identified 29 HLA-II associated HIV sequence polymorphisms or adaptations (HLA-AP in an African cohort of chronically HIV-infected individuals. Epitopes encompassing the predicted adaptation (AE or its non-adapted (NAE version were evaluated for immunogenicity. Using a CD8-depleted IFN-γ ELISpot assay, we determined that the magnitude of CD4+ T cell responses to the predicted epitopes in controllers was higher compared to non-controllers (p<0.0001. However, regardless of the group, the magnitude of responses to AE was lower as compared to NAE (p<0.0001. CD4+ T cell responses in patients with acute HIV infection (AHI demonstrated poor immunogenicity towards AE as compared to NAE encoded by their transmitted founder virus. Longitudinal data in AHI off antiretroviral therapy demonstrated sequence changes that were biologically confirmed to represent CD4+ escape mutations. These data demonstrate an innovative application of HLA-associated polymorphisms to identify biologically relevant CD4+ epitopes and suggests CD4+ T cells are active participants in driving HIV evolution.

  2. A comparison of computational models with and without genotyping for prediction of response to second-line HIV therapy

    NARCIS (Netherlands)

    Revell, A. D.; Boyd, M. A.; Wang, D.; Emery, S.; Gazzard, B.; Reiss, P.; van Sighem, A. I.; Montaner, J. S.; Lane, H. C.; Larder, B. A.

    2014-01-01

    We compared the use of computational models developed with and without HIV genotype vs. genotyping itself to predict effective regimens for patients experiencing first-line virological failure. Two sets of models predicted virological response for 99 three-drug regimens for patients on a failing

  3. Perturbation of B Cell Gene Expression Persists in HIV-Infected Children Despite Effective Antiretroviral Therapy and Predicts H1N1 Response.

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    Cotugno, Nicola; De Armas, Lesley; Pallikkuth, Suresh; Rinaldi, Stefano; Issac, Biju; Cagigi, Alberto; Rossi, Paolo; Palma, Paolo; Pahwa, Savita

    2017-01-01

    Despite effective antiretroviral therapy (ART), HIV-infected individuals with apparently similar clinical and immunological characteristics can vary in responsiveness to vaccinations. However, molecular mechanisms responsible for such impairment, as well as biomarkers able to predict vaccine responsiveness in HIV-infected children, remain unknown. Following the hypothesis that a B cell qualitative impairment persists in HIV-infected children (HIV) despite effective ART and phenotypic B cell immune reconstitution, the aim of the current study was to investigate B cell gene expression of HIV compared to age-matched healthy controls (HCs) and to determine whether distinct gene expression patterns could predict the ability to respond to influenza vaccine. To do so, we analyzed prevaccination transcriptional levels of a 96-gene panel in equal numbers of sort-purified B cell subsets (SPBS) isolated from peripheral blood mononuclear cells using multiplexed RT-PCR. Immune responses to H1N1 antigen were determined by hemaglutination inhibition and memory B cell ELISpot assays following trivalent-inactivated influenza vaccination (TIV) for all study participants. Although there were no differences in terms of cell frequencies of SPBS between HIV and HC, the groups were distinguishable based upon gene expression analyses. Indeed, a 28-gene signature, characterized by higher expression of genes involved in the inflammatory response and immune activation was observed in activated memory B cells (CD27 + CD21 - ) from HIV when compared to HC despite long-term viral control (>24 months). Further analysis, taking into account H1N1 responses after TIV in HIV participants, revealed that a 25-gene signature in resting memory (RM) B cells (CD27 + CD21 + ) was able to distinguish vaccine responders from non-responders (NR). In fact, prevaccination RM B cells of responders showed a higher expression of gene sets involved in B cell adaptive immune responses ( APRIL, BTK, BLIMP1 ) and

  4. Computational models can predict response to HIV therapy without a genotype and may reduce treatment failure in different resource-limited settings

    NARCIS (Netherlands)

    Revell, A. D.; Wang, D.; Wood, R.; Morrow, C.; Tempelman, H.; Hamers, R. L.; Alvarez-Uria, G.; Streinu-Cercel, A.; Ene, L.; Wensing, A. M. J.; DeWolf, F.; Nelson, M.; Montaner, J. S.; Lane, H. C.; Larder, B. A.

    2013-01-01

    Genotypic HIV drug-resistance testing is typically 6065 predictive of response to combination antiretroviral therapy (ART) and is valuable for guiding treatment changes. Genotyping is unavailable in many resource-limited settings (RLSs). We aimed to develop models that can predict response to ART

  5. Merck Ad5/HIV induces broad innate immune activation that predicts CD8⁺ T-cell responses but is attenuated by preexisting Ad5 immunity.

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    Zak, Daniel E; Andersen-Nissen, Erica; Peterson, Eric R; Sato, Alicia; Hamilton, M Kristina; Borgerding, Joleen; Krishnamurty, Akshay T; Chang, Joanne T; Adams, Devin J; Hensley, Tiffany R; Salter, Alexander I; Morgan, Cecilia A; Duerr, Ann C; De Rosa, Stephen C; Aderem, Alan; McElrath, M Juliana

    2012-12-11

    To better understand how innate immune responses to vaccination can lead to lasting protective immunity, we used a systems approach to define immune signatures in humans over 1 wk following MRKAd5/HIV vaccination that predicted subsequent HIV-specific T-cell responses. Within 24 h, striking increases in peripheral blood mononuclear cell gene expression associated with inflammation, IFN response, and myeloid cell trafficking occurred, and lymphocyte-specific transcripts decreased. These alterations were corroborated by marked serum inflammatory cytokine elevations and egress of circulating lymphocytes. Responses of vaccinees with preexisting adenovirus serotype 5 (Ad5) neutralizing antibodies were strongly attenuated, suggesting that enhanced HIV acquisition in Ad5-seropositive subgroups in the Step Study may relate to the lack of appropriate innate activation rather than to increased systemic immune activation. Importantly, patterns of chemoattractant cytokine responses at 24 h and alterations in 209 peripheral blood mononuclear cell transcripts at 72 h were predictive of subsequent induction and magnitude of HIV-specific CD8(+) T-cell responses. This systems approach provides a framework to compare innate responses induced by vectors, as shown here by contrasting the more rapid, robust response to MRKAd5/HIV with that to yellow fever vaccine. When applied iteratively, the findings may permit selection of HIV vaccine candidates eliciting innate immune response profiles more likely to drive HIV protective immunity.

  6. CD4/CD8 Ratio and KT Ratio Predict Yellow Fever Vaccine Immunogenicity in HIV-Infected Patients.

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    Avelino-Silva, Vivian I; Miyaji, Karina T; Hunt, Peter W; Huang, Yong; Simoes, Marisol; Lima, Sheila B; Freire, Marcos S; Caiaffa-Filho, Helio H; Hong, Marisa A; Costa, Dayane Alves; Dias, Juliana Zanatta C; Cerqueira, Natalia B; Nishiya, Anna Shoko; Sabino, Ester Cerdeira; Sartori, Ana M; Kallas, Esper G

    2016-12-01

    HIV-infected individuals have deficient responses to Yellow Fever vaccine (YFV) and may be at higher risk for adverse events (AE). Chronic immune activation-characterized by low CD4/CD8 ratio or high indoleamine 2,3-dioxygenase-1 (IDO) activity-may influence vaccine response in this population. We prospectively assessed AE, viremia by the YFV virus and YF-specific neutralizing antibodies (NAb) in HIV-infected (CD4>350) and -uninfected adults through 1 year after vaccination. The effect of HIV status on initial antibody response to YFV was measured during the first 3 months following vaccination, while the effect on persistence of antibody response was measured one year following vaccination. We explored CD4/CD8 ratio, IDO activity (plasma kynurenine/tryptophan [KT] ratio) and viremia by Human Pegivirus as potential predictors of NAb response to YFV among HIV-infected participants with linear mixed models. 12 HIV-infected and 45-uninfected participants were included in the final analysis. HIV was not significantly associated with AE, YFV viremia or NAb titers through the first 3 months following vaccination. However, HIV-infected participants had 0.32 times the NAb titers observed for HIV-uninfected participants at 1 year following YFV (95% CI 0.13 to 0.83, p = 0.021), independent of sex, age and prior vaccination. In HIV-infected participants, each 10% increase in CD4/CD8 ratio predicted a mean 21% higher post-baseline YFV Nab titer (p = 0.024). Similarly, each 10% increase in KT ratio predicted a mean 21% lower post-baseline YFV Nab titer (p = 0.009). Viremia by Human Pegivirus was not significantly associated with NAb titers. HIV infection appears to decrease the durability of NAb responses to YFV, an effect that may be predicted by lower CD4/CD8 ratio or higher KT ratio.

  7. HIV-1 vaccine-induced T-cell responses cluster in epitope hotspots that differ from those induced in natural infection with HIV-1.

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    Hertz, Tomer; Ahmed, Hasan; Friedrich, David P; Casimiro, Danilo R; Self, Steven G; Corey, Lawrence; McElrath, M Juliana; Buchbinder, Susan; Horton, Helen; Frahm, Nicole; Robertson, Michael N; Graham, Barney S; Gilbert, Peter

    2013-01-01

    Several recent large clinical trials evaluated HIV vaccine candidates that were based on recombinant adenovirus serotype 5 (rAd-5) vectors expressing HIV-derived antigens. These vaccines primarily elicited T-cell responses, which are known to be critical for controlling HIV infection. In the current study, we present a meta-analysis of epitope mapping data from 177 participants in three clinical trials that tested two different HIV vaccines: MRKAd-5 HIV and VRC-HIVAD014-00VP. We characterized the population-level epitope responses in these trials by generating population-based epitope maps, and also designed such maps using a large cohort of 372 naturally infected individuals. We used these maps to address several questions: (1) Are vaccine-induced responses randomly distributed across vaccine inserts, or do they cluster into immunodominant epitope hotspots? (2) Are the immunodominance patterns observed for these two vaccines in three vaccine trials different from one another? (3) Do vaccine-induced hotspots overlap with epitope hotspots induced by chronic natural infection with HIV-1? (4) Do immunodominant hotspots target evolutionarily conserved regions of the HIV genome? (5) Can epitope prediction methods be used to identify these hotspots? We found that vaccine responses clustered into epitope hotspots in all three vaccine trials and some of these hotspots were not observed in chronic natural infection. We also found significant differences between the immunodominance patterns generated in each trial, even comparing two trials that tested the same vaccine in different populations. Some of the vaccine-induced immunodominant hotspots were located in highly variable regions of the HIV genome, and this was more evident for the MRKAd-5 HIV vaccine. Finally, we found that epitope prediction methods can partially predict the location of vaccine-induced epitope hotspots. Our findings have implications for vaccine design and suggest a framework by which different

  8. Increased brain-predicted aging in treated HIV disease.

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    Cole, James H; Underwood, Jonathan; Caan, Matthan W A; De Francesco, Davide; van Zoest, Rosan A; Leech, Robert; Wit, Ferdinand W N M; Portegies, Peter; Geurtsen, Gert J; Schmand, Ben A; Schim van der Loeff, Maarten F; Franceschi, Claudio; Sabin, Caroline A; Majoie, Charles B L M; Winston, Alan; Reiss, Peter; Sharp, David J

    2017-04-04

    To establish whether HIV disease is associated with abnormal levels of age-related brain atrophy, by estimating apparent brain age using neuroimaging and exploring whether these estimates related to HIV status, age, cognitive performance, and HIV-related clinical parameters. A large sample of virologically suppressed HIV-positive adults (n = 162, age 45-82 years) and highly comparable HIV-negative controls (n = 105) were recruited as part of the Comorbidity in Relation to AIDS (COBRA) collaboration. Using T1-weighted MRI scans, a machine-learning model of healthy brain aging was defined in an independent cohort (n = 2,001, aged 18-90 years). Neuroimaging data from HIV-positive and HIV-negative individuals were then used to estimate brain-predicted age; then brain-predicted age difference (brain-PAD = brain-predicted brain age - chronological age) scores were calculated. Neuropsychological and clinical assessments were also carried out. HIV-positive individuals had greater brain-PAD score (mean ± SD 2.15 ± 7.79 years) compared to HIV-negative individuals (-0.87 ± 8.40 years; b = 3.48, p brain-PAD score was associated with decreased performance in multiple cognitive domains (information processing speed, executive function, memory) and general cognitive performance across all participants. Brain-PAD score was not associated with age, duration of HIV infection, or other HIV-related measures. Increased apparent brain aging, predicted using neuroimaging, was observed in HIV-positive adults, despite effective viral suppression. Furthermore, the magnitude of increased apparent brain aging related to cognitive deficits. However, predicted brain age difference did not correlate with chronological age or duration of HIV infection, suggesting that HIV disease may accentuate rather than accelerate brain aging. Copyright © 2017 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.

  9. CD4/CD8 Ratio and KT Ratio Predict Yellow Fever Vaccine Immunogenicity in HIV-Infected Patients

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    Hunt, Peter W.; Huang, Yong; Simoes, Marisol; Lima, Sheila B.; Freire, Marcos S.; Caiaffa-Filho, Helio H.; Hong, Marisa A.; Costa, Dayane Alves; Dias, Juliana Zanatta C.; Cerqueira, Natalia B.; Nishiya, Anna Shoko; Sabino, Ester Cerdeira; Sartori, Ana M.; Kallas, Esper G.

    2016-01-01

    Background HIV-infected individuals have deficient responses to Yellow Fever vaccine (YFV) and may be at higher risk for adverse events (AE). Chronic immune activation–characterized by low CD4/CD8 ratio or high indoleamine 2,3-dioxygenase-1 (IDO) activity—may influence vaccine response in this population. Methods We prospectively assessed AE, viremia by the YFV virus and YF-specific neutralizing antibodies (NAb) in HIV-infected (CD4>350) and -uninfected adults through 1 year after vaccination. The effect of HIV status on initial antibody response to YFV was measured during the first 3 months following vaccination, while the effect on persistence of antibody response was measured one year following vaccination. We explored CD4/CD8 ratio, IDO activity (plasma kynurenine/tryptophan [KT] ratio) and viremia by Human Pegivirus as potential predictors of NAb response to YFV among HIV-infected participants with linear mixed models. Results 12 HIV-infected and 45-uninfected participants were included in the final analysis. HIV was not significantly associated with AE, YFV viremia or NAb titers through the first 3 months following vaccination. However, HIV–infected participants had 0.32 times the NAb titers observed for HIV-uninfected participants at 1 year following YFV (95% CI 0.13 to 0.83, p = 0.021), independent of sex, age and prior vaccination. In HIV-infected participants, each 10% increase in CD4/CD8 ratio predicted a mean 21% higher post-baseline YFV Nab titer (p = 0.024). Similarly, each 10% increase in KT ratio predicted a mean 21% lower post-baseline YFV Nab titer (p = 0.009). Viremia by Human Pegivirus was not significantly associated with NAb titers. Conclusions HIV infection appears to decrease the durability of NAb responses to YFV, an effect that may be predicted by lower CD4/CD8 ratio or higher KT ratio. PMID:27941965

  10. Network-based prediction and analysis of HIV dependency factors.

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    T M Murali

    2011-09-01

    Full Text Available HIV Dependency Factors (HDFs are a class of human proteins that are essential for HIV replication, but are not lethal to the host cell when silenced. Three previous genome-wide RNAi experiments identified HDF sets with little overlap. We combine data from these three studies with a human protein interaction network to predict new HDFs, using an intuitive algorithm called SinkSource and four other algorithms published in the literature. Our algorithm achieves high precision and recall upon cross validation, as do the other methods. A number of HDFs that we predict are known to interact with HIV proteins. They belong to multiple protein complexes and biological processes that are known to be manipulated by HIV. We also demonstrate that many predicted HDF genes show significantly different programs of expression in early response to SIV infection in two non-human primate species that differ in AIDS progression. Our results suggest that many HDFs are yet to be discovered and that they have potential value as prognostic markers to determine pathological outcome and the likelihood of AIDS development. More generally, if multiple genome-wide gene-level studies have been performed at independent labs to study the same biological system or phenomenon, our methodology is applicable to interpret these studies simultaneously in the context of molecular interaction networks and to ask if they reinforce or contradict each other.

  11. Computational models can predict response to HIV therapy without a genotype and may reduce treatment failure in different resource-limited settings.

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    Revell, A D; Wang, D; Wood, R; Morrow, C; Tempelman, H; Hamers, R L; Alvarez-Uria, G; Streinu-Cercel, A; Ene, L; Wensing, A M J; DeWolf, F; Nelson, M; Montaner, J S; Lane, H C; Larder, B A

    2013-06-01

    Genotypic HIV drug-resistance testing is typically 60%-65% predictive of response to combination antiretroviral therapy (ART) and is valuable for guiding treatment changes. Genotyping is unavailable in many resource-limited settings (RLSs). We aimed to develop models that can predict response to ART without a genotype and evaluated their potential as a treatment support tool in RLSs. Random forest models were trained to predict the probability of response to ART (≤400 copies HIV RNA/mL) using the following data from 14 891 treatment change episodes (TCEs) after virological failure, from well-resourced countries: viral load and CD4 count prior to treatment change, treatment history, drugs in the new regimen, time to follow-up and follow-up viral load. Models were assessed by cross-validation during development, with an independent set of 800 cases from well-resourced countries, plus 231 cases from Southern Africa, 206 from India and 375 from Romania. The area under the receiver operating characteristic curve (AUC) was the main outcome measure. The models achieved an AUC of 0.74-0.81 during cross-validation and 0.76-0.77 with the 800 test TCEs. They achieved AUCs of 0.58-0.65 (Southern Africa), 0.63 (India) and 0.70 (Romania). Models were more accurate for data from the well-resourced countries than for cases from Southern Africa and India (P < 0.001), but not Romania. The models identified alternative, available drug regimens predicted to result in virological response for 94% of virological failures in Southern Africa, 99% of those in India and 93% of those in Romania. We developed computational models that predict virological response to ART without a genotype with comparable accuracy to genotyping with rule-based interpretation. These models have the potential to help optimize antiretroviral therapy for patients in RLSs where genotyping is not generally available.

  12. Potential Impact of a Free Online HIV Treatment Response Prediction System for Reducing Virological Failures and Drug Costs after Antiretroviral Therapy Failure in a Resource-Limited Setting

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    Andrew D. Revell

    2013-01-01

    Full Text Available Objective. Antiretroviral drug selection in resource-limited settings is often dictated by strict protocols as part of a public health strategy. The objective of this retrospective study was to examine if the HIV-TRePS online treatment prediction tool could help reduce treatment failure and drug costs in such settings. Methods. The HIV-TRePS computational models were used to predict the probability of response to therapy for 206 cases of treatment change following failure in India. The models were used to identify alternative locally available 3-drug regimens, which were predicted to be effective. The costs of these regimens were compared to those actually used in the clinic. Results. The models predicted the responses to treatment of the cases with an accuracy of 0.64. The models identified alternative drug regimens that were predicted to result in improved virological response and lower costs than those used in the clinic in 85% of the cases. The average annual cost saving was $364 USD per year (41%. Conclusions. Computational models that do not require a genotype can predict and potentially avoid treatment failure and may reduce therapy costs. The use of such a system to guide therapeutic decision-making could confer health economic benefits in resource-limited settings.

  13. Polyfunctional HIV-Specific Antibody Responses Are Associated with Spontaneous HIV Control.

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    Margaret E Ackerman

    2016-01-01

    Full Text Available Elite controllers (ECs represent a unique model of a functional cure for HIV-1 infection as these individuals develop HIV-specific immunity able to persistently suppress viremia. Because accumulating evidence suggests that HIV controllers generate antibodies with enhanced capacity to drive antibody-dependent cellular cytotoxicity (ADCC that may contribute to viral containment, we profiled an array of extra-neutralizing antibody effector functions across HIV-infected populations with varying degrees of viral control to define the characteristics of antibodies associated with spontaneous control. While neither the overall magnitude of antibody titer nor individual effector functions were increased in ECs, a more functionally coordinated innate immune-recruiting response was observed. Specifically, ECs demonstrated polyfunctional humoral immune responses able to coordinately recruit ADCC, other NK functions, monocyte and neutrophil phagocytosis, and complement. This functionally coordinated response was associated with qualitatively superior IgG3/IgG1 responses, whereas HIV-specific IgG2/IgG4 responses, prevalent among viremic subjects, were associated with poorer overall antibody activity. Rather than linking viral control to any single activity, this study highlights the critical nature of functionally coordinated antibodies in HIV control and associates this polyfunctionality with preferential induction of potent antibody subclasses, supporting coordinated antibody activity as a goal in strategies directed at an HIV-1 functional cure.

  14. Upper Gastrointestinal Symptoms Predictive of Candida Esophagitis and Erosive Esophagitis in HIV and Non-HIV Patients

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    Takahashi, Yuta; Nagata, Naoyoshi; Shimbo, Takuro; Nishijima, Takeshi; Watanabe, Koji; Aoki, Tomonori; Sekine, Katsunori; Okubo, Hidetaka; Watanabe, Kazuhiro; Sakurai, Toshiyuki; Yokoi, Chizu; Mimori, Akio; Oka, Shinichi; Uemura, Naomi; Akiyama, Junichi

    2015-01-01

    Abstract Upper gastrointestinal (GI) symptoms are common in both HIV and non-HIV-infected patients, but the difference of GI symptom severity between 2 groups remains unknown. Candida esophagitis and erosive esophagitis, 2 major types of esophagitis, are seen in both HIV and non-HIV-infected patients, but differences in GI symptoms that are predictive of esophagitis between 2 groups remain unknown. We aimed to determine whether GI symptoms differ between HIV-infected and non-HIV-infected patients, and identify specific symptoms of candida esophagitis and erosive esophagitis between 2 groups. We prospectively enrolled 6011 patients (HIV, 430; non-HIV, 5581) who underwent endoscopy and completed questionnaires. Nine upper GI symptoms (epigastric pain, heartburn, acid regurgitation, hunger cramps, nausea, early satiety, belching, dysphagia, and odynophagia) were evaluated using a 7-point Likert scale. Associations between esophagitis and symptoms were analyzed by the multivariate logistic regression model adjusted for age, sex, and proton pump inhibitors. Endoscopy revealed GI-organic diseases in 33.4% (2010/6.011) of patients. The prevalence of candida esophagitis and erosive esophagitis was 11.2% and 12.1% in HIV-infected patients, respectively, whereas it was 2.9% and 10.7 % in non-HIV-infected patients, respectively. After excluding GI-organic diseases, HIV-infected patients had significantly (P symptom scores for heartburn, hunger cramps, nausea, early satiety, belching, dysphagia, and odynophagia than non-HIV-infected patients. In HIV-infected patients, any symptom was not significantly associated with CD4 cell count. In multivariate analysis, none of the 9 GI symptoms were associated with candida esophagitis in HIV-infected patients, whereas dysphagia and odynophagia were independently (P HIV-infected patients. However, heartburn and acid regurgitation were independently (P symptom scores were reliable in both HIV (α, 0.86) and non-HIV-infected patients

  15. Performance of immunological response in predicting virological failure.

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    Ingole, Nayana; Mehta, Preeti; Pazare, Amar; Paranjpe, Supriya; Sarkate, Purva

    2013-03-01

    In HIV-infected individuals on antiretroviral therapy (ART), the decision on when to switch from first-line to second-line therapy is dictated by treatment failure, and this can be measured in three ways: clinically, immunologically, and virologically. While viral load (VL) decreases and CD4 cell increases typically occur together after starting ART, discordant responses may be seen. Hence the current study was designed to determine the immunological and virological response to ART and to evaluate the utility of immunological response to predict virological failure. All treatment-naive HIV-positive individuals aged >18 years who were eligible for ART were enrolled and assessed at baseline, 6 months, and 12 months clinically and by CD4 cell count and viral load estimations. The patients were categorized as showing concordant favorable (CF), immunological only (IO), virological only (VO), and concordant unfavorable responses (CU). The efficiency of immunological failure to predict virological failure was analyzed across various levels of virological failure (VL>50, >500, and >5,000 copies/ml). At 6 months, 87(79.81%), 7(5.5%), 13 (11.92%), and 2 (1.83%) patients and at 12 months 61(69.3%), 9(10.2%), 16 (18.2%), and 2 (2.3%) patients had CF, IO, VO, and CU responses, respectively. Immunological failure criteria had a very low sensitivity (11.1-40%) and positive predictive value (8.3-25%) to predict virological failure. Immunological criteria do not accurately predict virological failure resulting in significant misclassification of therapeutic responses. There is an urgent need for inclusion of viral load testing in the initiation and monitoring of ART.

  16. Anti-HIV Antibody Responses and the HIV Reservoir Size during Antiretroviral Therapy.

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    Sulggi A Lee

    Full Text Available A major challenge to HIV eradication strategies is the lack of an accurate measurement of the total burden of replication-competent HIV (the "reservoir". We assessed the association of anti-HIV antibody responses and the estimated size of the reservoir during antiretroviral therapy (ART.We evaluated anti-HIV antibody profiles using luciferase immunoprecipitation systems (LIPS assay in relation to several blood-based HIV reservoir measures: total and 2-LTR DNA (rtPCR or droplet digital PCR; integrated DNA (Alu PCR; unspliced RNA (rtPCR, multiply-spliced RNA (TILDA, residual plasma HIV RNA (single copy PCR, and replication-competent virus (outgrowth assay. We also assessed total HIV DNA and RNA in gut-associated lymphoid tissue (rtPCR. Spearman correlations and linear regressions were performed using log-transformed blood- or tissue-based reservoir measurements as predictors and log-transformed antibody levels as outcome variables.Among 51 chronically HIV-infected ART-suppressed participants (median age = 57, nadir CD4+ count = 196 cells/mm3, ART duration = 9 years, the most statistically significant associations were between antibody responses to integrase and HIV RNA in gut-associated lymphoid tissue (1.17 fold-increase per two-fold RNA increase, P = 0.004 and between antibody responses to matrix and integrated HIV DNA in resting CD4+ T cells (0.35 fold-decrease per two-fold DNA increase, P = 0.003. However, these associations were not statistically significant after a stringent Bonferroni-adjustment of P<0.00045. Multivariate models including age and duration of ART did not markedly alter results.Our findings suggest that anti-HIV antibody responses may reflect the size of the HIV reservoir during chronic treated HIV disease, possibly via antigen recognition in reservoir sites. Larger, prospective studies are needed to validate the utility of antibody levels as a measure of the total body burden of HIV during treatment.

  17. HIV-1 DNA predicts disease progression and post-treatment virological control

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    Williams, James P; Hurst, Jacob; Stöhr, Wolfgang; Robinson, Nicola; Brown, Helen; Fisher, Martin; Kinloch, Sabine; Cooper, David; Schechter, Mauro; Tambussi, Giuseppe; Fidler, Sarah; Carrington, Mary; Babiker, Abdel; Weber, Jonathan

    2014-01-01

    In HIV-1 infection, a population of latently infected cells facilitates viral persistence despite antiretroviral therapy (ART). With the aim of identifying individuals in whom ART might induce a period of viraemic control on stopping therapy, we hypothesised that quantification of the pool of latently infected cells in primary HIV-1 infection (PHI) would predict clinical progression and viral replication following ART. We measured HIV-1 DNA in a highly characterised randomised population of individuals with PHI. We explored associations between HIV-1 DNA and immunological and virological markers of clinical progression, including viral rebound in those interrupting therapy. In multivariable analyses, HIV-1 DNA was more predictive of disease progression than plasma viral load and, at treatment interruption, predicted time to plasma virus rebound. HIV-1 DNA may help identify individuals who could safely interrupt ART in future HIV-1 eradication trials. Clinical trial registration: ISRCTN76742797 and EudraCT2004-000446-20 DOI: http://dx.doi.org/10.7554/eLife.03821.001 PMID:25217531

  18. Gastrointestinal immune responses in HIV infected subjects

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    LRR Castello-Branco

    1996-06-01

    Full Text Available The gut associated lymphoid tissue is responsible for specific responses to intestinal antigens. During HIV infection, mucosal immune deficiency may account for the gastrointestinal infections. In this review we describe the humoral and cellular mucosal immune responses in normal and HIV-infected subjects.

  19. Improved darunavir genotypic mutation score predicting treatment response for patients infected with HIV-1 subtype B and non-subtype B receiving a salvage regimen

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    De Luca, Andrea; Flandre, Philippe; Dunn, David

    2016-01-01

    OBJECTIVES: The objective of this study was to improve the prediction of the impact of HIV-1 protease mutations in different viral subtypes on virological response to darunavir. METHODS: Darunavir-containing treatment change episodes (TCEs) in patients previously failing PIs were selected from...... was derived based on best subset least squares estimation with mutational weights corresponding to regression coefficients. Virological outcome prediction accuracy was compared with that from existing genotypic resistance interpretation systems (GISs) (ANRS 2013, Rega 9.1.0 and HIVdb 7.0). RESULTS: TCEs were...

  20. TREX1 Knockdown Induces an Interferon Response to HIV that Delays Viral Infection in Humanized Mice

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    Lee Adam Wheeler

    2016-05-01

    Full Text Available Despite their antiviral effect, the in vivo effect of interferons on HIV transmission is difficult to predict, because interferons also activate and recruit HIV-susceptible cells to sites of infection. HIV does not normally induce type I interferons in infected cells, but does if TREX1 is knocked down. Here, we investigated the effect of topical TREX1 knockdown and local interferon production on HIV transmission in human cervicovaginal explants and humanized mice. In explants in which TREX1 was knocked down, HIV induced interferons, which blocked infection. In humanized mice, even though TREX1 knockdown increased infiltrating immune cells, it delayed viral replication for 3–4 weeks. Similarly intravaginal application of type I interferons the day before HIV infection induced interferon responsive genes, reduced inflammation, and decreased viral replication. However, intravenous interferon enhanced inflammation and infection. Thus, in models of human sexual transmission, a localized interferon response inhibits HIV transmission but systemic interferons do not.

  1. Is response to anti-hepatitis C virus treatment predictive of mortality in hepatitis C virus/HIV-positive patients?

    DEFF Research Database (Denmark)

    Peters, Lars; Raben, Dorthe

    2017-01-01

    BACKGROUND: Long-term clinical outcomes after hepatitis C virus (HCV) treatment of HIV/HCV patients are not well described. We aimed to compare the risk of all-cause and liver-related death (LRD) according to HCV treatment response in HIV/HCV patients in the multicohort study Collaboration...... of Observational HIV Epidemiological Research in Europe. METHODS: All patients who had started pegylated interferon + ribavirin (baseline) and followed for at least 72 weeks after baseline were included. Patients were categorized into three response groups depending on treatment duration and HCV-RNA measured...... in the window 24-72 weeks after baseline. Patients who received at least 24 weeks of therapy were defined as responders if their last HCV-RNA measured between 24 and 72 weeks after baseline was negative, and having 'unknown response' if HCV-RNA was unknown. Nonresponders were treated for less than 24 weeks...

  2. Predictive markers of survival in HIV-seropositive and HIV-seronegative Tanzanian patients with extrapulmonary tuberculosis

    NARCIS (Netherlands)

    Richter, C.; Koelemay, M. J.; Swai, A. B.; Perenboom, R.; Mwakyusa, D. H.; Oosting, J.

    1995-01-01

    Prediction of survival in Tanzanian patients with extrapulmonary tuberculosis (TB). To evaluate the prognostic value of clinical and laboratory parameters on survival in human immunodeficiency virus (HIV) seropositive and HIV seronegative patients with extrapulmonary TB. Over an 8-month period 192

  3. Predicting the short-term risk of diabetes in HIV-positive patients

    DEFF Research Database (Denmark)

    Petoumenos, Kathy; Worm, Signe Westring; Fontas, Eric

    2012-01-01

    Introduction: HIV-positive patients receiving combination antiretroviral therapy (cART) frequently experience metabolic complications such as dyslipidemia and insulin resistance, as well as lipodystrophy, increasing the risk of cardiovascular disease (CVD) and diabetes mellitus (DM). Rates of DM ......). Factors predictive of DM included higher glucose, body mass index (BMI) and triglyceride levels, and older age. Among HIV-related factors, recent CD4 counts of...... and other glucose-associated disorders among HIV-positive patients have been reported to range between 2 and 14%, and in an ageing HIV-positive population, the prevalence of DM is expected to continue to increase. This study aims to develop a model to predict the short-term (six-month) risk of DM in HIV...

  4. Prediction of HIV-1 sensitivity to broadly neutralizing antibodies shows a trend towards resistance over time.

    Science.gov (United States)

    Hake, Anna; Pfeifer, Nico

    2017-10-01

    Treatment with broadly neutralizing antibodies (bNAbs) has proven effective against HIV-1 infections in humanized mice, non-human primates, and humans. Due to the high mutation rate of HIV-1, resistance testing of the patient's viral strains to the bNAbs is still inevitable. So far, bNAb resistance can only be tested in expensive and time-consuming neutralization experiments. Here, we introduce well-performing computational models that predict the neutralization response of HIV-1 to bNAbs given only the envelope sequence of the virus. Using non-linear support vector machines based on a string kernel, the models learnt even the important binding sites of bNAbs with more complex epitopes, i.e., the CD4 binding site targeting bNAbs, proving thereby the biological relevance of the models. To increase the interpretability of the models, we additionally provide a new kind of motif logo for each query sequence, visualizing those residues of the test sequence that influenced the prediction outcome the most. Moreover, we predicted the neutralization sensitivity of around 34,000 HIV-1 samples from different time points to a broad range of bNAbs, enabling the first analysis of HIV resistance to bNAbs on a global scale. The analysis showed for many of the bNAbs a trend towards antibody resistance over time, which had previously only been discovered for a small non-representative subset of the global HIV-1 population.

  5. HIV-1-Specific Antibody Response and Function after DNA Prime and Recombinant Adenovirus 5 Boost HIV Vaccine in HIV-Infected Subjects.

    Directory of Open Access Journals (Sweden)

    Johannes S Gach

    Full Text Available Little is known about the humoral immune response against DNA prime-recombinant adenovirus 5 (rAd5 boost HIV vaccine among HIV-infected patients on long-term suppressive antiretroviral therapy (ART. Previous studies emphasized cellular immune responses; however, current research suggests both cellular and humoral responses are likely required for a successful therapeutic vaccine. Thus, we aimed to understand antibody response and function induced by vaccination of ART-treated HIV-1-infected patients with immune recovery. All subjects participated in EraMune 02, an open-label randomized clinical trial of ART intensification followed by a six plasmid DNA prime (envA, envB, envC, gagB, polB, nefB and rAd5 boost HIV vaccine with matching inserts. Antibody binding levels were determined with a recently developed microarray approach. We also analyzed neutralization efficiency and antibody-dependent cellular cytotoxicity (ADCC. We found that the DNA prime-rAd5 boost vaccine induced a significant cross-clade HIV-specific antibody response, which correlated with antibody neutralization efficiency. However, despite the increase in antibody binding levels, the vaccine did not significantly stimulate neutralization or ADCC responses. This finding was also reflected by a lack of change in total CD4+ cell associated HIV DNA in those who received the vaccine. Our results have important implications for further therapeutic vaccine design and administration, especially in HIV-1 infected patients, as boosting of preexisting antibody responses are unlikely to lead to clearance of latent proviruses in the HIV reservoir.

  6. Prediction of the Secondary Structure of HIV-1 gp120

    DEFF Research Database (Denmark)

    Hansen, Jan; Lund, Ole; Nielsen, Jens O.

    1996-01-01

    Fourier transform infrared spectroscopy. The predicted secondary structure of gp120 compared well with data from NMR analysis of synthetic peptides from the V3 loop and the C4 region. As a first step towards modeling the tertiary structure of gp120, the predicted secondary structure may guide the design......The secondary structure of HIV-1 gp120 was predicted using multiple alignment and a combination of two independent methods based on neural network and nearest-neighbor algorithms. The methods agreed on the secondary structure for 80% of the residues in BH10 gp120. Six helices were predicted in HIV...

  7. Understanding the response of large South African companies to HIV/AIDS.

    Science.gov (United States)

    Dickinson, D; Stevens, M

    2005-07-01

    This paper provides a framework analysing the response of South African companies to HIV/AIDS. Drawing on three case studies of companies, each with over 20,000 South African-based employees, we identify six 'drivers' that influence corporate behaviour regarding HIV/AIDS: legal requirements, voluntary regulation, business costs, social pressures, visibility of the disease, and individuals within companies. We suggest that costs calculations, while possibly underestimating indirect and macro-implications, are not key in driving company responses to HIV/AIDS. The law and voluntary regulation have influenced, but not determined, the response of companies to HIV/AIDS. Social pressures on companies are of importance, but the scale and complexity of need in South Africa has seen the deflecting of this driver. Of greater reference in determining responses has been the social pressure of other companies' responses. The general visibility of the AIDS epidemic is also a significant factor in explaining companies' responses to HIV/AIDS. Moreover, the visibility of HIV/AIDS within companies has influenced the responses of often relatively weak, internal agents who have been attempting to drive companies' HIV/AIDS programmes. We conclude that external drivers--legal requirements, economic performance, and social pressures--have framed corporate responses to HIV/AIDS to a degree, but have generally been weak. Moreover, there has been relatively little synergy between these external drivers and the internal drivers--voluntary regulation, visibility, and company HIV/AIDS 'champions'--that could propel companies into pro-active, bold responses to HIV/AIDS.

  8. Aligning faith-based and national HIV/AIDS prevention responses? Factors influencing the HIV/AIDS prevention policy process and response of faith-based NGOs in Tanzania.

    Science.gov (United States)

    Morgan, Rosemary; Green, Andrew; Boesten, Jelke

    2014-05-01

    Faith-based organizations (FBOs) have a long tradition of providing HIV/AIDS prevention and mitigation services in Africa. The overall response of FBOs, however, has been controversial, particularly in regard to HIV/AIDS prevention and FBO's rejection of condom use and promotion, which can conflict with and negatively influence national HIV/AIDS prevention response efforts. This article reports the findings from a study that explored the factors influencing the HIV/AIDS prevention policy process within faith-based non-governmental organizations (NGOs) of different faiths. These factors were examined within three faith-based NGOs in Dar es Salaam, Tanzania-a Catholic, Anglican and Muslim organization. The research used an exploratory, qualitative case-study approach, and employed a health policy analysis framework, examining the context, actor and process factors and how they interact to form content in terms of policy and its implementation within each organization. Three key factors were found to influence faith-based NGOs' HIV/AIDS prevention response in terms of both policy and its implementation: (1) the faith structure in which the organizations are a part, (2) the presence or absence of organizational policy and (3) the professional nature of the organizations and its actors. The interaction between these factors, and how actors negotiate between them, was found to shape the organizations' HIV/AIDS prevention response. This article reports on these factors and analyses the different HIV/AIDS prevention responses found within each organization. By understanding the factors that influence faith-based NGOs' HIV/AIDS prevention policy process, the overall faith-based response to HIV/AIDS, and how it corresponds to national response efforts, is better understood. It is hoped that by doing so the government will be better able to identify how to best work with FBOs to meet national HIV/AIDS prevention targets, improving the overall role of FBOs in the fight against

  9. The relationship between negative responses to HIV status disclosure and psychosocial outcomes among people living with HIV.

    Science.gov (United States)

    Cama, Elena; Brener, Loren; Slavin, Sean; de Wit, John

    2017-07-01

    This report examines rates of HIV status disclosure and negative responses to disclosure among people living with HIV in Australia. Among 697 people living with HIV, most (>90%) had disclosed their status to friends, sexual partners and health providers. Almost a third had not disclosed to family, and half had not told any work colleagues. Negative responses to disclosure (e.g. blame, rejection) by all groups were associated with increased HIV-related stigma, psychological distress and diminished social support and health satisfaction. These results shed light on rates of disclosure among people living with HIV in Australia and the adverse health impacts of negative responses to disclosure.

  10. Innovative financing for HIV response in sub–Saharan Africa

    Directory of Open Access Journals (Sweden)

    Rifat Atun

    2016-06-01

    Full Text Available In 2015 around 15 million people living with HIV were receiving antiretroviral treatment (ART in sub–Saharan Africa. Sustained provision of ART, though both prudent and necessary, creates substantial long–term fiscal obligations for countries affected by HIV/AIDS. As donor assistance for health remains constrained, novel financing mechanisms are needed to augment funding domestic sources. We explore how Innovative Financing has been used to co–finance domestic HIV/AIDS responses. Based on analysis of non–health sectors, we identify innovative financing instruments that could be used in the HIV response.

  11. An update to the HIV-TRePS system: the development of new computational models that do not require a genotype to predict HIV treatment outcomes.

    Science.gov (United States)

    Revell, Andrew D; Wang, Dechao; Wood, Robin; Morrow, Carl; Tempelman, Hugo; Hamers, Raph; Alvarez-Uria, Gerardo; Streinu-Cercel, Adrian; Ene, Luminita; Wensing, Annemarie; Reiss, Peter; van Sighem, Ard I; Nelson, Mark; Emery, Sean; Montaner, Julio S G; Lane, H Clifford; Larder, Brendan A

    2014-04-01

    The optimal individualized selection of antiretroviral drugs in resource-limited settings is challenging because of the limited availability of drugs and genotyping. Here we describe the development of the latest computational models to predict the response to combination antiretroviral therapy without a genotype, for potential use in such settings. Random forest models were trained to predict the probability of a virological response to therapy (HIV RNA/mL) following virological failure using the following data from 22,567 treatment-change episodes including 1090 from southern Africa: baseline viral load and CD4 cell count, treatment history, drugs in the new regimen, time to follow-up and follow-up viral load. The models were assessed during cross-validation and with an independent global test set of 1000 cases including 100 from southern Africa. The models' accuracy [area under the receiver-operating characteristic curve (AUC)] was evaluated and compared with genotyping using rules-based interpretation systems for those cases with genotypes available. The models achieved AUCs of 0.79-0.84 (mean 0.82) during cross-validation, 0.80 with the global test set and 0.78 with the southern African subset. The AUCs were significantly lower (0.56-0.57) for genotyping. The models predicted virological response to HIV therapy without a genotype as accurately as previous models that included a genotype. They were accurate for cases from southern Africa and significantly more accurate than genotyping. These models will be accessible via the online treatment support tool HIV-TRePS and have the potential to help optimize antiretroviral therapy in resource-limited settings where genotyping is not generally available.

  12. Abia State HIV epidemic and response: challenges and prospects.

    Science.gov (United States)

    Onyeonoro, Ugochukwu Uchenna; Emelumadu, Obiageli Fidelia; Nwamoh, Uche Ngozi; Ukegbu, Andrew Ugwunna; Okafor, Godwin Oc

    2014-11-13

    Since the first seroprevalence survey in 1999, the HIV prevalence in Abia State has increased from 1.8% to 7.3% in 2010. The state is currently experiencing a generalized epidemic, with most transmission occurring through heterosexual low-risk sex. Drivers of the epidemic include low knowledge of HIV prevention, low risk perception, predominantly male factor-driven risky sexual behavior, and low condom use. This study reviewed the state HIV epidemic trend in relation to response, sought to identify the gaps between the epidemic and response, and recommended measures to strengthen the state response.

  13. Predictive Validity And Usefulness Of Visual Scanning Task In Hiv ...

    African Journals Online (AJOL)

    The visual scanning task is a useful screening tool for brain damage in HIV/AIDS by inference from impairment of visual information processing and disturbances in perceptual mental strategies. There is progressive neuro-cognitive decline as the disease worsens. Keywords: brain, cognition, HIV/AIDS, predictive validity, ...

  14. Broad, Intense Anti-Human Immunodeficiency Virus (HIV) Ex Vivo CD8+ Responses in HIV Type 1-Infected Patients: Comparison with Anti-Epstein-Barr Virus Responses and Changes during Antiretroviral Therapy

    Science.gov (United States)

    Dalod, Marc; Dupuis, Marion; Deschemin, Jean-Christophe; Sicard, Didier; Salmon, Dominique; Delfraissy, Jean-Francois; Venet, Alain; Sinet, Martine; Guillet, Jean-Gerard

    1999-01-01

    The ex vivo antiviral CD8+ repertoires of 34 human immunodeficiency virus (HIV)-seropositive patients with various CD4+ T-cell counts and virus loads were analyzed by gamma interferon enzyme-linked immunospot assay, using peptides derived from HIV type 1 and Epstein-Barr virus (EBV). Most patients recognized many HIV peptides, with markedly high frequencies, in association with all the HLA class I molecules tested. We found no correlation between the intensity of anti-HIV CD8+ responses and the CD4+ counts or virus load. In contrast, the polyclonality of anti-HIV CD8+ responses was positively correlated with the CD4+ counts. The anti-EBV responses were significantly less intense than the anti-HIV responses and were positively correlated with the CD4+ counts. Longitudinal follow-up of several patients revealed the remarkable stability of the anti-HIV and anti-EBV CD8+ responses in two patients with stable CD4+ counts, while both antiviral responses decreased in two patients with obvious progression toward disease. Last, highly active antiretroviral therapy induced marked decreases in the number of anti-HIV CD8+ T cells, while the anti-EBV responses increased. These findings emphasize the magnitude of the ex vivo HIV-specific CD8+ responses at all stages of HIV infection and suggest that the CD8+ hyperlymphocytosis commonly observed in HIV infection is driven mainly by virus replication, through intense, continuous activation of HIV-specific CD8+ T cells until ultimate progression toward disease. Nevertheless, highly polyclonal anti-HIV CD8+ responses may be associated with a better clinical status. Our data also suggest that a decrease of anti-EBV CD8+ responses may occur with depletion of CD4+ T cells, but this could be restored by highly active antiretroviral treatment. PMID:10438796

  15. Predicting substance abuse among youth with, or at high risk for, HIV

    NARCIS (Netherlands)

    Huba, GJ; Melchoir, LA; Greenberg, B; Trevithick, L; Feudo, R; Tierney, S; Sturdevant, M; Hodgins, A; Remafedi, G; Woods, ER; Wallace, M; Schneir, A; Kawata, AK; Brady, RE; Singer, B; Marconi, K; Wright, E; Panter, AT

    This article describes data from 4,111 males and 4,085 females participating in 10 HIV/AIDS service demonstration projects. The sample was diverse in age, gender, ethnicity, HIV status, and risk for HIV transmission. Logistic regression was used to determine the attributes that best predict

  16. Interdisciplinary Evaluation of Broadly-Reactive HLA Class II Restricted Epitopes Eliciting HIV-Specific CD4+T Cell Responses

    DEFF Research Database (Denmark)

    Buggert, M.; Norström, M.; Lundegaard, Claus

    2011-01-01

    , the functional and immunodominant discrepancies of CD4+ T cell responses targeting promiscuous MHC II restricted HIV epitopes remains poorly defined. Thus, utilization of interdisciplinary approaches might aid revealing broadly- reactive peptides eliciting CD4 + T cell responses. Methods: We utilized the novel...... bioinformatic prediction program NetMHCIIpan to select 64 optimized MHC II restricted epitopes located in the HIV Gag, Pol, Env, Nef and Tat regions. The epitopes were selected to cover the global diversity of the virus (multiple subtypes) and the human immune system(diverse MHC II types). Optimized...

  17. Mathematical modeling of escape of HIV from cytotoxic T lymphocyte responses

    International Nuclear Information System (INIS)

    Ganusov, Vitaly V; Neher, Richard A; Perelson, Alan S

    2013-01-01

    Human immunodeficiency virus (HIV-1 or simply HIV) induces a persistent infection, which in the absence of treatment leads to AIDS and death in almost all infected individuals. HIV infection elicits a vigorous immune response starting about 2–3 weeks postinfection that can lower the amount of virus in the body, but which cannot eradicate the virus. How HIV establishes a chronic infection in the face of a strong immune response remains poorly understood. It has been shown that HIV is able to rapidly change its proteins via mutation to evade recognition by virus-specific cytotoxic T lymphocytes (CTLs). Typically, an HIV-infected patient will generate 4–12 CTL responses specific for parts of viral proteins called epitopes. Such CTL responses lead to strong selective pressure to change the viral sequences encoding these epitopes so as to avoid CTL recognition. Indeed, the viral population ‘escapes’ from about half of the CTL responses by mutation in the first year. Here we review experimental data on HIV evolution in response to CTL pressure, mathematical models developed to explain this evolution, and highlight problems associated with the data and previous modeling efforts. We show that estimates of the strength of the epitope-specific CTL response depend on the method used to fit models to experimental data and on the assumptions made regarding how mutants are generated during infection. We illustrate that allowing CTL responses to decay over time may improve the model fit to experimental data and provides higher estimates of the killing efficacy of HIV-specific CTLs. We also propose a novel method for simultaneously estimating the killing efficacy of multiple CTL populations specific for different epitopes of HIV using stochastic simulations. Lastly, we show that current estimates of the efficacy at which HIV-specific CTLs clear virus-infected cells can be improved by more frequent sampling of viral sequences and by combining data on sequence evolution with

  18. Predicting the short-term risk of diabetes in HIV-positive patients

    DEFF Research Database (Denmark)

    Petoumenos, Kathy; Worm, Signe W; Fontas, Eric

    2012-01-01

    HIV-positive patients receiving combination antiretroviral therapy (cART) frequently experience metabolic complications such as dyslipidemia and insulin resistance, as well as lipodystrophy, increasing the risk of cardiovascular disease (CVD) and diabetes mellitus (DM). Rates of DM and other...... glucose-associated disorders among HIV-positive patients have been reported to range between 2 and 14%, and in an ageing HIV-positive population, the prevalence of DM is expected to continue to increase. This study aims to develop a model to predict the short-term (six-month) risk of DM in HIV...

  19. Sepsis in HIV-infected patients; epidemiology and host response

    NARCIS (Netherlands)

    Huson, M.A.M.

    2016-01-01

    In this thesis, we examined the impact of HIV infection on the epidemiology (Part I) of sepsis, and host response (Part II) to sepsis. We studied sepsis patients in Gabon, a setting with a high prevalence of HIV, and in Dutch intensive care units (ICUs). In Part I, we found that HIV positive

  20. Upper Gastrointestinal Symptoms Predictive of Candida Esophagitis and Erosive Esophagitis in HIV and Non-HIV Patients: An Endoscopy-Based Cross-Sectional Study of 6011 Patients.

    Science.gov (United States)

    Takahashi, Yuta; Nagata, Naoyoshi; Shimbo, Takuro; Nishijima, Takeshi; Watanabe, Koji; Aoki, Tomonori; Sekine, Katsunori; Okubo, Hidetaka; Watanabe, Kazuhiro; Sakurai, Toshiyuki; Yokoi, Chizu; Mimori, Akio; Oka, Shinichi; Uemura, Naomi; Akiyama, Junichi

    2015-11-01

    Upper gastrointestinal (GI) symptoms are common in both HIV and non-HIV-infected patients, but the difference of GI symptom severity between 2 groups remains unknown. Candida esophagitis and erosive esophagitis, 2 major types of esophagitis, are seen in both HIV and non-HIV-infected patients, but differences in GI symptoms that are predictive of esophagitis between 2 groups remain unknown. We aimed to determine whether GI symptoms differ between HIV-infected and non-HIV-infected patients, and identify specific symptoms of candida esophagitis and erosive esophagitis between 2 groups.We prospectively enrolled 6011 patients (HIV, 430; non-HIV, 5581) who underwent endoscopy and completed questionnaires. Nine upper GI symptoms (epigastric pain, heartburn, acid regurgitation, hunger cramps, nausea, early satiety, belching, dysphagia, and odynophagia) were evaluated using a 7-point Likert scale. Associations between esophagitis and symptoms were analyzed by the multivariate logistic regression model adjusted for age, sex, and proton pump inhibitors.Endoscopy revealed GI-organic diseases in 33.4% (2010/6.011) of patients. The prevalence of candida esophagitis and erosive esophagitis was 11.2% and 12.1% in HIV-infected patients, respectively, whereas it was 2.9% and 10.7 % in non-HIV-infected patients, respectively. After excluding GI-organic diseases, HIV-infected patients had significantly (P symptom scores for heartburn, hunger cramps, nausea, early satiety, belching, dysphagia, and odynophagia than non-HIV-infected patients. In HIV-infected patients, any symptom was not significantly associated with CD4 cell count. In multivariate analysis, none of the 9 GI symptoms were associated with candida esophagitis in HIV-infected patients, whereas dysphagia and odynophagia were independently (P HIV-infected patients. However, heartburn and acid regurgitation were independently (P symptom scores were reliable in both HIV (α, 0.86) and non-HIV-infected patients (α, 0.85).This

  1. Possible Biomarkers for the Early Detection of HIV-associated Heart Diseases: A Proteomics and Bioinformatics Prediction

    Directory of Open Access Journals (Sweden)

    Suraiya Rasheed

    2015-01-01

    Full Text Available The frequency of cardiovascular disorders is increasing in HIV-infected individuals despite a significant reduction in the viral load by antiretroviral therapies (ART. Since the CD4+ T-cells are responsible for the viral load as well as immunological responses, we hypothesized that chronic HIV-infection of T-cells produces novel proteins/enzymes that cause cardiac dysfunctions. To identify specific factors that might cause cardiac disorders without the influence of numerous cofactors produced by other pathogenic microorganisms that co-inhabit most HIV-infected individuals, we analyzed genome-wide proteomes of a CD4+ T-cell line at different stages of HIV replication and cell growth over >6 months. Subtractive analyses of several hundred differentially regulated proteins from HIV-infected and uninfected counterpart cells and comparisons with proteins expressed from the same cells after treating with the antiviral drug Zidovudine/AZT and inhibiting virus replication, identified a well-coordinated network of 12 soluble/diffusible proteins in HIV-infected cells. Functional categorization, bioinformatics and statistical analyses of each protein predicted that the expression of cardiac-specific Ca2+ kinase together with multiple Ca2+ release channels causes a sustained overload of Ca2+ in the heart which induces fetal/cardiac myosin heavy chains (MYH6 and MYH7 and a myosin light-chain kinase. Each of these proteins has been shown to cause cardiac stress, arrhythmia, hypertrophic signaling, cardiomyopathy and heart failure (p = 8 × 10−11. Translational studies using the newly discovered proteins produced by HIV infection alone would provide additional biomarkers that could be added to the conventional markers for an early diagnosis and/or development of specific therapeutic interventions for heart diseases in HIV-infected individuals.

  2. Three-Year Durability of Immune Responses Induced by HIV-DNA and HIV-Modified Vaccinia Virus Ankara and Effect of a Late HIV-Modified Vaccinia Virus Ankara Boost in Tanzanian Volunteers.

    Science.gov (United States)

    Joachim, Agricola; Munseri, Patricia J; Nilsson, Charlotta; Bakari, Muhammad; Aboud, Said; Lyamuya, Eligius F; Tecleab, Teghesti; Liakina, Valentina; Scarlatti, Gabriella; Robb, Merlin L; Earl, Patricia L; Moss, Bernard; Wahren, Britta; Mhalu, Fred; Ferrari, Guido; Sandstrom, Eric; Biberfeld, Gunnel

    2017-08-01

    We explored the duration of immune responses and the effect of a late third HIV-modified vaccinia virus Ankara (MVA) boost in HIV-DNA primed and HIV-MVA boosted Tanzanian volunteers. Twenty volunteers who had previously received three HIV-DNA and two HIV-MVA immunizations were given a third HIV-MVA immunization 3 years after the second HIV-MVA boost. At the time of the third HIV-MVA, 90% of the vaccinees had antibodies to HIV-1 subtype C gp140 (median titer 200) and 85% to subtype B gp160 (median titer 100). The majority of vaccinees had detectable antibody-dependent cellular cytotoxicity (ADCC)-mediating antibodies, 70% against CRF01_AE virus-infected cells (median titer 239) and 84% against CRF01_AE gp120-coated cells (median titer 499). A high proportion (74%) of vaccinees had IFN-γ ELISpot responses, 63% to Gag and 42% to Env, 3 years after the second HIV-MVA boost. After the third HIV-MVA, there was an increase in Env-binding antibodies and ADCC-mediating antibodies relative to the response seen at the time of the third HIV-MVA vaccination, p < .0001 and p < .05, respectively. The frequency of IFN-γ ELISpot responses increased to 95% against Gag or Env and 90% to both Gag and Env, p = .064 and p = .002, respectively. In conclusion, the HIV-DNA prime/HIV-MVA boost regimen elicited potent antibody and cellular immune responses with remarkable durability, and a third HIV-MVA immunization significantly boosted both antibody and cellular immune responses relative to the levels detected at the time of the third HIV-MVA, but not to higher levels than after the second HIV-MVA.

  3. Plasma Metabolomics Biosignature According to HIV Stage of Infection, Pace of Disease Progression, Viremia Level and Immunological Response to Treatment.

    Directory of Open Access Journals (Sweden)

    Bruno Scarpellini

    Full Text Available We evaluated plasma samples HIV-infected individuals with different phenotypic profile among five HIV-infected elite controllers and five rapid progressors after recent HIV infection and one year later and from 10 individuals subjected to antiretroviral therapy, five of whom were immunological non-responders (INR, before and after one year of antiretroviral treatment compared to 175 samples from HIV-negative patients. A targeted quantitative tandem mass spectrometry metabolomics approach was used in order to determine plasma metabolomics biosignature that may relate to HIV infection, pace of HIV disease progression, and immunological response to treatment.Twenty-five unique metabolites were identified, including five metabolites that could distinguish rapid progressors and INRs at baseline. Severe deregulation in acylcarnitine and sphingomyelin metabolism compatible with mitochondrial deficiencies was observed. β-oxidation and sphingosine-1-phosphate-phosphatase-1 activity were down-regulated, whereas acyl-alkyl-containing phosphatidylcholines and alkylglyceronephosphate synthase levels were elevated in INRs. Evidence that elite controllers harbor an inborn error of metabolism (late-onset multiple acyl-coenzyme A dehydrogenase deficiency [MADD] was detected.Blood-based markers from metabolomics show a very high accuracy of discriminating HIV infection between varieties of controls and have the ability to predict rapid disease progression or poor antiretroviral immunological response. These metabolites can be used as biomarkers of HIV natural evolution or treatment response and provide insight into the mechanisms of the disease.

  4. Plasma Metabolomics Biosignature According to HIV Stage of Infection, Pace of Disease Progression, Viremia Level and Immunological Response to Treatment.

    Science.gov (United States)

    Scarpellini, Bruno; Zanoni, Michelle; Sucupira, Maria Cecilia Araripe; Truong, Hong-Ha M; Janini, Luiz Mario Ramos; Segurado, Ismael Dale Cotrin; Diaz, Ricardo Sobhie

    2016-01-01

    We evaluated plasma samples HIV-infected individuals with different phenotypic profile among five HIV-infected elite controllers and five rapid progressors after recent HIV infection and one year later and from 10 individuals subjected to antiretroviral therapy, five of whom were immunological non-responders (INR), before and after one year of antiretroviral treatment compared to 175 samples from HIV-negative patients. A targeted quantitative tandem mass spectrometry metabolomics approach was used in order to determine plasma metabolomics biosignature that may relate to HIV infection, pace of HIV disease progression, and immunological response to treatment. Twenty-five unique metabolites were identified, including five metabolites that could distinguish rapid progressors and INRs at baseline. Severe deregulation in acylcarnitine and sphingomyelin metabolism compatible with mitochondrial deficiencies was observed. β-oxidation and sphingosine-1-phosphate-phosphatase-1 activity were down-regulated, whereas acyl-alkyl-containing phosphatidylcholines and alkylglyceronephosphate synthase levels were elevated in INRs. Evidence that elite controllers harbor an inborn error of metabolism (late-onset multiple acyl-coenzyme A dehydrogenase deficiency [MADD]) was detected. Blood-based markers from metabolomics show a very high accuracy of discriminating HIV infection between varieties of controls and have the ability to predict rapid disease progression or poor antiretroviral immunological response. These metabolites can be used as biomarkers of HIV natural evolution or treatment response and provide insight into the mechanisms of the disease.

  5. Variable context Markov chains for HIV protease cleavage site prediction.

    Science.gov (United States)

    Oğul, Hasan

    2009-06-01

    Deciphering the knowledge of HIV protease specificity and developing computational tools for detecting its cleavage sites in protein polypeptide chain are very desirable for designing efficient and specific chemical inhibitors to prevent acquired immunodeficiency syndrome. In this study, we developed a generative model based on a generalization of variable order Markov chains (VOMC) for peptide sequences and adapted the model for prediction of their cleavability by certain proteases. The new method, called variable context Markov chains (VCMC), attempts to identify the context equivalence based on the evolutionary similarities between individual amino acids. It was applied for HIV-1 protease cleavage site prediction problem and shown to outperform existing methods in terms of prediction accuracy on a common dataset. In general, the method is a promising tool for prediction of cleavage sites of all proteases and encouraged to be used for any kind of peptide classification problem as well.

  6. Innovative financing for HIV response in sub-Saharan Africa.

    Science.gov (United States)

    Atun, Rifat; Silva, Sachin; Ncube, Mthuli; Vassall, Anna

    2016-06-01

    In 2015 around 15 million people living with HIV were receiving antiretroviral treatment (ART) in sub-Saharan Africa. Sustained provision of ART, though both prudent and necessary, creates substantial long-term fiscal obligations for countries affected by HIV/AIDS. As donor assistance for health remains constrained, novel financing mechanisms are needed to augment funding domestic sources. We explore how Innovative Financing has been used to co-finance domestic HIV/AIDS responses. Based on analysis of non-health sectors, we identify innovative financing instruments that could be used in the HIV response. We undertook a systematic review to identify innovative financing instruments used for (1) domestic HIV/AIDS financing in sub-Saharan Africa (2) international health financing and (3) financing in non-health sectors. We analyzed peer-reviewed and grey literature published between 2002 and 2014. We examined the nature and volume of funds mobilized with innovative financing, then in consultation with leading experts, identified instruments that held potential for financing the HIV response. Our analysis revealed three innovative financing instruments in use: Zimbabwe's AIDS Trust Fund (a tax/levy-based instrument), Botswana's National HIV/AIDS Prevention Support (BNAPS) International Bank for Reconstruction and Development (IBRD) Buy-Down (a debt conversion instrument), and Côte d'Ivoire's Debt2Health Debt Swap Agreement (a debt conversion instrument). Zimbabwe's AIDS Trust Fund generated US$ 52.7 million between 2008 and 2011, Botswana's IBRD Buy-Down generated US$ 20 million, and Côte d'Ivoire's Debt2Health Debt Swap Agreement generated US$ 27 million, at least half of which was to be invested in HIV/AIDS programs. Four additional categories of innovative financing instruments met our criteria for future use: (1) remittances and diaspora bonds (2) social and development impact bonds (3) sovereign wealth funds (4) risk and credit guarantees. A limited number of

  7. Predictive and prognostic properties of TB-LAM among HIV-positive patients initiating ART in Johannesburg, South Africa.

    Science.gov (United States)

    d'Elia, Alexander; Evans, Denise; McNamara, Lynne; Berhanu, Rebecca; Sanne, Ian; Lönnermark, Elisabet

    2015-01-01

    While the diagnostic properties of the TB LAM urine assay (LAM) have been well-described, little is known about its predictive and prognostic properties at ART initiation in a routine clinic setting. We describe the predictive and prognostic properties of LAM in HIV-positive patients initiating ART at an urban hospital in Johannesburg, South Africa. Retrospective study of HIV-positive adults (>18 years) who initiated standard first-line ART between February 2012 and April 2013 and had a LAM test at initiation. In HIV-positive patients with no known TB at ART initiation, we assessed the sensitivity, specificity and positive/negative likelihood ratios of LAM to predict incident TB within 6 months of ART initiation. In addition, in patients with a TB diagnosis and on TB treatment ART initiation, we measured the CD4 response at 6 months on ART. Of the 274 patients without TB at ART initiation, 65% were female with median CD4 count of 213 cells/mm(3). Among the 14 (5.1%) patients who developed active TB, none were urine LAM +ve at baseline. LAM had poor sensitivity (0.0% 95% CI 0.00-23.2) to predict incident TB within 6 months of initiation. We analyzed 22 patients with a confirmed TB diagnosis at initiation separately. Of these, LAM +ve patients (27%) showed lower CD4 gains compared to LAM negative patients (median increase 103 vs 199 cells/mm(3); p = 0.08). LAM has limited value for accurately predicting incident TB in patients with higher CD4 counts after ART initiation. LAM may help identify TB/HIV co-infected patients at ART initiation who respond more slowly to treatment and require targeted interventions to improve treatment outcomes. Larger studies with longer patient follow-up are needed.

  8. Immunological responses during a virologically failing antiretroviral regimen are associated with in vivo synonymous mutation rates of HIV type-1 env

    DEFF Research Database (Denmark)

    Mens, Helene; Jørgensen, Louise Bruun; Kronborg, Gitte

    2009-01-01

    BACKGROUND: Little is known about the underlying causes of differences in immunological response to antiretroviral therapy during multidrug-resistant (MDR) HIV type-1 (HIV-1) infection. This study aimed to identify virological factors associated with immunological response during therapy failure...... for analysis. In a longitudinal mixed-effects model, plasma HIV-1 RNA only tended to predict immunological response (P=0.06), whereas minor protease inhibitor (PI) and nucleoside reverse transcriptase (NRTI) mutations at baseline correlated significantly with CD4+ T-cell count slopes (r= -0.56, P=0.04 and r......= -0.64, P=0.008, respectively). Interestingly, synonymous mutations of env correlated inversely with CD4+ T-cell count slopes (r=-0.60; P=0.01) and individuals with codons under positive selection had significantly better CD4+ T-cell responses than individuals without (0.42 versus -5.34; P=0...

  9. Impact of aging and HIV infection on serologic response to seasonal influenza vaccination.

    Science.gov (United States)

    Pallikkuth, Suresh; De Armas, Lesley R; Pahwa, Rajendra; Rinaldi, Stefano; George, Varghese K; Sanchez, Celeste M; Pan, Li; Dickinson, Gordon; Rodriguez, Allan; Fischl, Margaret; Alcaide, Maria; Pahwa, Savita

    2018-02-08

    To determine influence of age and HIV infection on influenza vaccine responses. Evaluate serologic response to seasonal trivalent influenza vaccine (TIV) as the immunologic outcome in HIV-infected (HIV) and age-matched HIV negative (HIV) adults. During 2013-2016, 151 virologically controlled HIV individuals on antiretroviral therapy and 164 HIV volunteers grouped by age as young (<40 years), middle aged (40-59 years) and old (≥60 years) were administered TIV and investigated for serum antibody response to vaccine antigens. At prevaccination (T0) titers were in seroprotective range in more than 90% of participants. Antibody titers increased in all participants postvaccination but frequency of classified vaccine responders to individual or all three vaccine antigens at 3-4 weeks was higher in HIV than HIV adults with the greatest differences manifesting in the young age group. Of the three vaccine strains in TIV, antibody responses at T2 were weakest against H3N2 with those to H1N1 and B antigens dominating. Among the age groups, the titers for H1N1 and B were lowest in old age, with evidence of an age-associated interaction in HIV persons with antibody to B antigen. Greater frequencies of vaccine nonresponders are seen in HIV young compared with HIV adults and the observed age-associated interaction for B antigen in HIV persons are supportive of the concept of premature immune senescence in controlled HIV infection. High-potency influenza vaccination recommended for healthy aging could be considered for HIV adults of all ages.

  10. Predicting Bevirimat resistance of HIV-1 from genotype

    Directory of Open Access Journals (Sweden)

    Hoffmann Daniel

    2010-01-01

    Full Text Available Abstract Background Maturation inhibitors are a new class of antiretroviral drugs. Bevirimat (BVM was the first substance in this class of inhibitors entering clinical trials. While the inhibitory function of BVM is well established, the molecular mechanisms of action and resistance are not well understood. It is known that mutations in the regions CS p24/p2 and p2 can cause phenotypic resistance to BVM. We have investigated a set of p24/p2 sequences of HIV-1 of known phenotypic resistance to BVM to test whether BVM resistance can be predicted from sequence, and to identify possible molecular mechanisms of BVM resistance in HIV-1. Results We used artificial neural networks and random forests with different descriptors for the prediction of BVM resistance. Random forests with hydrophobicity as descriptor performed best and classified the sequences with an area under the Receiver Operating Characteristics (ROC curve of 0.93 ± 0.001. For the collected data we find that p2 sequence positions 369 to 376 have the highest impact on resistance, with positions 370 and 372 being particularly important. These findings are in partial agreement with other recent studies. Apart from the complex machine learning models we derived a number of simple rules that predict BVM resistance from sequence with surprising accuracy. According to computational predictions based on the data set used, cleavage sites are usually not shifted by resistance mutations. However, we found that resistance mutations could shorten and weaken the α-helix in p2, which hints at a possible resistance mechanism. Conclusions We found that BVM resistance of HIV-1 can be predicted well from the sequence of the p2 peptide, which may prove useful for personalized therapy if maturation inhibitors reach clinical practice. Results of secondary structure analysis are compatible with a possible route to BVM resistance in which mutations weaken a six-helix bundle discovered in recent experiments

  11. Circulating sCD14 is associated with virological response to pegylated-interferon-alpha/ribavirin treatment in HIV/HCV co-infected patients.

    Directory of Open Access Journals (Sweden)

    Giulia Marchetti

    Full Text Available Microbial translocation (MT through the gut accounts for immune activation and CD4+ loss in HIV and may influence HCV disease progression in HIV/HCV co-infection. We asked whether increased MT and immune activation may hamper anti-HCV response in HIV/HCV patients.98 HIV/HCV patients who received pegylated-alpha-interferon (peg-INF-alpha/ribavirin were retrospectively analyzed. Baseline MT (lipopolysaccharide, LPS, host response to MT (sCD14, CD38+HLA-DR+CD4+/CD8+, HCV genotype, severity of liver disease were assessed according to Early Virological Response (EVR: HCV-RNA <50 IU/mL at week 12 of therapy or ≥2 log(10 reduction from baseline after 12 weeks of therapy and Sustained Virological Response (SVR: HCV-RNA <50 IU/mL 24 weeks after end of therapy. Mann-Whitney/Chi-square test and Pearson's correlation were used. Multivariable regression was performed to determine factors associated with EVR/SVR.71 patients displayed EVR; 41 SVR. Patients with HCV genotypes 1-4 and cirrhosis presented a trend to higher sCD14, compared to patients with genotypes 2-3 (p = 0.053 and no cirrhosis (p = 0.052. EVR and SVR patients showed lower levels of circulating sCD14 (p = 0.0001, p = 0.026, respectively, but similar T-cell activation compared to Non-EVR (Null Responders, NR and Non-SVR (N-SVR subjects. sCD14 resulted the main predictive factor of EVR (0.145 for each sCD14 unit more, 95%CI 0.031-0.688, p = 0.015. SVR was associated only with HCV genotypes 2-3 (AOR 0.022 for genotypes 1-4 vs 2-3, 95%CI 0.001-0.469, p = 0.014.In HIV/HCV patients sCD14 correlates with the severity of liver disease and predicts early response to peg-INF-alpha/ribavirin, suggesting MT-driven immune activation as pathway of HIV/HCV co-infection and response to therapy.

  12. Structural similarity-based predictions of protein interactions between HIV-1 and Homo sapiens

    Directory of Open Access Journals (Sweden)

    Gomez Shawn M

    2010-04-01

    Full Text Available Abstract Background In the course of infection, viruses such as HIV-1 must enter a cell, travel to sites where they can hijack host machinery to transcribe their genes and translate their proteins, assemble, and then leave the cell again, all while evading the host immune system. Thus, successful infection depends on the pathogen's ability to manipulate the biological pathways and processes of the organism it infects. Interactions between HIV-encoded and human proteins provide one means by which HIV-1 can connect into cellular pathways to carry out these survival processes. Results We developed and applied a computational approach to predict interactions between HIV and human proteins based on structural similarity of 9 HIV-1 proteins to human proteins having known interactions. Using functional data from RNAi studies as a filter, we generated over 2000 interaction predictions between HIV proteins and 406 unique human proteins. Additional filtering based on Gene Ontology cellular component annotation reduced the number of predictions to 502 interactions involving 137 human proteins. We find numerous known interactions as well as novel interactions showing significant functional relevance based on supporting Gene Ontology and literature evidence. Conclusions Understanding the interplay between HIV-1 and its human host will help in understanding the viral lifecycle and the ways in which this virus is able to manipulate its host. The results shown here provide a potential set of interactions that are amenable to further experimental manipulation as well as potential targets for therapeutic intervention.

  13. Seroconversion for human herpesvirus 8 during HIV infection is highly predictive of Kaposi's sarcoma

    NARCIS (Netherlands)

    Renwick, N.; Halaby, T.; Weverling, G. J.; Dukers, N. H.; Simpson, G. R.; Coutinho, R. A.; Lange, J. M.; Schulz, T. F.; Goudsmit, J.

    1998-01-01

    The finding of antibodies against human herpesvirus 8 (HHV-8) is associated with the occurrence of Kaposi's sarcoma in persons infected with HIV. However, the predictive value of HHV-8 antibodies for Kaposi's sarcoma in HIV infection is unknown. The Amsterdam Cohort Studies on HIV infection and AIDS

  14. Increased sequence diversity coverage improves detection of HIV-Specific T cell responses

    DEFF Research Database (Denmark)

    Frahm, N.; Kaufmann, D.E.; Yusim, K.

    2007-01-01

    The accurate identification of HIV-specific T cell responses is important for determining the relationship between immune response, viral control, and disease progression. HIV-specific immune responses are usually measured using peptide sets based on consensus sequences, which frequently miss res...

  15. Innovative financing for HIV response in sub–Saharan Africa

    Science.gov (United States)

    Atun, Rifat; Silva, Sachin; Ncube, Mthuli; Vassall, Anna

    2016-01-01

    Background In 2015 around 15 million people living with HIV were receiving antiretroviral treatment (ART) in sub–Saharan Africa. Sustained provision of ART, though both prudent and necessary, creates substantial long–term fiscal obligations for countries affected by HIV/AIDS. As donor assistance for health remains constrained, novel financing mechanisms are needed to augment funding domestic sources. We explore how Innovative Financing has been used to co–finance domestic HIV/AIDS responses. Based on analysis of non–health sectors, we identify innovative financing instruments that could be used in the HIV response. Methods We undertook a systematic review to identify innovative financing instruments used for (1) domestic HIV/AIDS financing in sub–Saharan Africa (2) international health financing and (3) financing in non–health sectors. We analyzed peer–reviewed and grey literature published between 2002 and 2014. We examined the nature and volume of funds mobilized with innovative financing, then in consultation with leading experts, identified instruments that held potential for financing the HIV response. Results Our analysis revealed three innovative financing instruments in use: Zimbabwe’s AIDS Trust Fund (a tax/levy–based instrument), Botswana’s National HIV/AIDS Prevention Support (BNAPS) International Bank for Reconstruction and Development (IBRD) Buy–Down (a debt conversion instrument), and Côte d'Ivoire's Debt2Health Debt Swap Agreement (a debt conversion instrument). Zimbabwe’s AIDS Trust Fund generated US$ 52.7 million between 2008 and 2011, Botswana’s IBRD Buy–Down generated US$ 20 million, and Côte d’Ivoire’s Debt2Health Debt Swap Agreement generated US$ 27 million, at least half of which was to be invested in HIV/AIDS programs. Four additional categories of innovative financing instruments met our criteria for future use: (1) remittances and diaspora bonds (2) social and development impact bonds (3) sovereign wealth

  16. Scaling-up HIV responses with key populations in West Africa.

    Science.gov (United States)

    Wheeler, Tisha; Wolf, R Cameron; Kapesa, Laurent; Cheng Surdo, Alison; Dallabetta, Gina

    2015-03-01

    Despite decades of HIV responses in pockets of West and Central Africa (WCA), the HIV response with key populations remains an understudied area. Recently, there has been a proliferation of studies highlighting epidemiologic and behavioral data that challenge attitudes of complacency among donors and country governments uncomfortable in addressing key populations. The articles in this series highlight new studies that provide a better understanding of the epidemiologic and structural burden facing key populations in the WCA region and how to improve responses through more effective targeting. Key populations face pervasive structural barriers including institutional and sexual violence and an intersection of stigma, criminalization, and marginalization as sexual minorities. Despite decades of smaller interventions that have shown the importance of integrated services for key populations, there remains incongruent provision of outreach or testing or family planning pointing to sustained risk. There remains an incongruent resource provision for key populations where they shoulder the burden of HIV and their access to services alone could turn around HIV epidemics within the region. These proximal and distal determinants must be addressed in regional efforts, led by the community, and resourced for scale, targeting those most at risk for the acquisition and transmission of HIV. This special issue builds the knowledge base for the region focusing on interventions that remove barriers to service access including treatment uptake for those living with HIV. Better analysis and use of data for strategic planning are shown to lead to more effective targeting of prevention, care, and HIV treatment programs with key populations. These articles further demonstrate the immediate need for comprehensive action to address HIV among key populations throughout the WCA region.

  17. Europe?s Shifting Response to HIV/AIDS

    OpenAIRE

    Smith, Julia

    2016-01-01

    Abstract Despite a history of championing HIV/AIDS as a human rights issue, and a rhetorical commitment to health as a human right, European states and institutions have shifted from a rights-based response to a risk management approach to HIV/AIDS since the economic recession of 2008. An interdisciplinary perspective is applied to analyze health policy changes at the national, regional, and global levels by drawing on data from key informant interviews, and institutional and civil society do...

  18. Ocular surface squamous neoplasia in HIV-positive and HIV-negative patients and response to 5-fluorouracil in Angola

    Directory of Open Access Journals (Sweden)

    Nutt RJ

    2014-12-01

    Full Text Available Robert J Nutt,1 John L Clements,2 William H Dean3 1Faculty of Medicine and Dentistry, University of Bristol, Bristol, UK; 2Boa Vista Eye Clinic, Benguela, Angola; 3Bristol Eye Hospital, Bristol, UK Background: Ocular surface squamous neoplasia (OSSN is becoming increasingly prevalent and aggressive in Sub-Saharan Africa. It is a phenomenon linked with human immunodeficiency virus (HIV infection, although association rates in Angola are currently unknown. A topical treatment that is effective in HIV-positive and HIV-negative individuals may be preferable to surgery in some contexts. We aimed to estimate the proportion of OSSN associated with HIV in Angola and to report on the success of topical 5-fluorouracil as a primary treatment in HIV-positive and HIV-negative patients.Methods: Photographs of OSSNs taken at presentation and following treatment with 5-fluorouracil in patients presenting to Boa Vista Eye Clinic, Angola, between October 2011 and July 2013 were grouped into HIV-positive and HIV-negative groups and analyzed to compare presenting features and treatment response. Eighty-one OSSNs were analyzed for clinical features and 24 met the inclusion criteria for analysis of treatment response.Results: Eighty-two patients presented with OSSN between October 2011 and July 2013. Twenty-one (26% were HIV-positive and typically had OSSNs that exhibited more pathological features than those in HIV-negative patients. Twenty-four (29% patients met the inclusion criteria for analysis of treatment response; of these, 26 (91% OSSNs in both groups displayed at least partial resolution after one treatment course. In the HIV-positive group, five of eight patients displayed complete resolution, two showed partial resolution, and one failed. In the HIV-negative group, five of 16 showed complete resolution, ten of 16 had partial resolution, and one failed.Conclusion: Individuals presenting with OSSN in Angola are more likely to have HIV infection compared

  19. Broadly Neutralizing Antibody Responses in a Large Longitudinal Sub-Saharan HIV Primary Infection Cohort.

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    Elise Landais

    2016-01-01

    Full Text Available Broadly neutralizing antibodies (bnAbs are thought to be a critical component of a protective HIV vaccine. However, designing vaccines immunogens able to elicit bnAbs has proven unsuccessful to date. Understanding the correlates and immunological mechanisms leading to the development of bnAb responses during natural HIV infection is thus critical to the design of a protective vaccine. The IAVI Protocol C program investigates a large longitudinal cohort of primary HIV-1 infection in Eastern and South Africa. Development of neutralization was evaluated in 439 donors using a 6 cross-clade pseudo-virus panel predictive of neutralization breadth on larger panels. About 15% of individuals developed bnAb responses, essentially between year 2 and year 4 of infection. Statistical analyses revealed no influence of gender, age or geographical origin on the development of neutralization breadth. However, cross-clade neutralization strongly correlated with high viral load as well as with low CD4 T cell counts, subtype-C infection and HLA-A*03(- genotype. A correlation with high overall plasma IgG levels and anti-Env IgG binding titers was also found. The latter appeared not associated with higher affinity, suggesting a greater diversity of the anti-Env responses in broad neutralizers. Broadly neutralizing activity targeting glycan-dependent epitopes, largely the N332-glycan epitope region, was detected in nearly half of the broad neutralizers while CD4bs and gp41-MPER bnAb responses were only detected in very few individuals. Together the findings suggest that both viral and host factors are critical for the development of bnAbs and that the HIV Env N332-glycan supersite may be a favorable target for vaccine design.

  20. Immunological Response of Hiv-Infected Children to Highly Active ...

    African Journals Online (AJOL)

    BACKGROUND: The effectiveness of highly active antiretroviral therapy (HAART) in children has not been well studied specially in developing countries where the burden of HIV is high. This study was aimed to assess the immunologic response of HIV-infected children to HAART at Pediatric ART Clinic Gondar University ...

  1. Information and communication: a library's local response to HIV/AIDS in Zambia.

    Science.gov (United States)

    Kanyengo, Christine Wamunyima

    2010-03-01

    To document and describe the University of Zambia Medical library's responses to the fight against HIV/AIDS in Zambia. The methodology adopted was a case study approach combined with an analysis of the literature such as annual reports and official documents. This was augmented by personal reflections of the author having worked at the Medical Library. The University of Zambia Medical library has over the years instituted and implemented HIV/AIDS information provision programmes that include the provision of information in various formats -- print or electronic and, in addition, capacity building in HIV/AIDS information literacy skills. A library's social responsibility calls for it to be part of national responses to crises that arise in society. As HIV/AIDS has affected every aspect of Zambian society prevention, treatment, care and support there is an understanding that the library's role should be using the critical and strategic resource at its disposal - information -- as part of their contribution to the fight against HIV/AIDS. In this context, libraries should source, collect, organize and disseminate information on HIV/AIDS in a way that is easily accessible to researchers, HIV/AIDS programme implementation agencies and the ordinary public.

  2. gCUP: rapid GPU-based HIV-1 co-receptor usage prediction for next-generation sequencing.

    Science.gov (United States)

    Olejnik, Michael; Steuwer, Michel; Gorlatch, Sergei; Heider, Dominik

    2014-11-15

    Next-generation sequencing (NGS) has a large potential in HIV diagnostics, and genotypic prediction models have been developed and successfully tested in the recent years. However, albeit being highly accurate, these computational models lack computational efficiency to reach their full potential. In this study, we demonstrate the use of graphics processing units (GPUs) in combination with a computational prediction model for HIV tropism. Our new model named gCUP, parallelized and optimized for GPU, is highly accurate and can classify >175 000 sequences per second on an NVIDIA GeForce GTX 460. The computational efficiency of our new model is the next step to enable NGS technologies to reach clinical significance in HIV diagnostics. Moreover, our approach is not limited to HIV tropism prediction, but can also be easily adapted to other settings, e.g. drug resistance prediction. The source code can be downloaded at http://www.heiderlab.de d.heider@wz-straubing.de. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  3. Factors predicting discordant virological and immunological responses to antiretroviral therapy in HIV-1 clade C infected Zulu/Xhosa in South Africa.

    Directory of Open Access Journals (Sweden)

    Boris Julg

    Full Text Available Factors predicting suboptimal CD4 cell recovery have been studied in HIV clade-B infected US and European populations. It is, however, uncertain to what extent these results are applicable to HIV clade-C infected African populations. Multivariate analysis using logistic regression and longitudinal analyses using mixed models were employed to assess the impact of age, gender, baseline CD4 cell count, hemoglobin, body mass index (BMI, tuberculosis and other opportunistic co-infections, and frequencies of regimen change on CD4 cell recovery at 12 and 30 months and on overtime change in CD4 cells among 442 virologically suppressed South Africans. Despite adequate virological response 37% (95% CI:32%-42% and 83% (95% CI:79%-86% of patients on antiretroviral therapy failed to restore CD4 cell counts ≥ 200 cells/mm(3 after 12 and ≥ 500 cells/mm(3 after 30 months, respectively, in this South African cohort. Critical risk factors for inadequate recovery were older age (p = 0.001 and nadir CD4 cell count at ART initiation (p<0.0001, while concurrent TB co-infection, BMI, baseline hemoglobin, gender and antiretroviral regimen were not significant risk factors. These data suggest that greater efforts are needed to identify and treat HAART-eligible patients prior to severe CD4 cell decline or achievement of advanced age.

  4. Factors predicting discordant virological and immunological responses to antiretroviral therapy in HIV-1 clade C infected Zulu/Xhosa in South Africa.

    Science.gov (United States)

    Julg, Boris; Poole, Danielle; Ghebremichael, Musie; Castilla, Carmen; Altfeld, Marcus; Sunpath, Henry; Murphy, Richard A; Walker, Bruce D

    2012-01-01

    Factors predicting suboptimal CD4 cell recovery have been studied in HIV clade-B infected US and European populations. It is, however, uncertain to what extent these results are applicable to HIV clade-C infected African populations. Multivariate analysis using logistic regression and longitudinal analyses using mixed models were employed to assess the impact of age, gender, baseline CD4 cell count, hemoglobin, body mass index (BMI), tuberculosis and other opportunistic co-infections, and frequencies of regimen change on CD4 cell recovery at 12 and 30 months and on overtime change in CD4 cells among 442 virologically suppressed South Africans. Despite adequate virological response 37% (95% CI:32%-42%) and 83% (95% CI:79%-86%) of patients on antiretroviral therapy failed to restore CD4 cell counts ≥ 200 cells/mm(3) after 12 and ≥ 500 cells/mm(3) after 30 months, respectively, in this South African cohort. Critical risk factors for inadequate recovery were older age (p = 0.001) and nadir CD4 cell count at ART initiation (p<0.0001), while concurrent TB co-infection, BMI, baseline hemoglobin, gender and antiretroviral regimen were not significant risk factors. These data suggest that greater efforts are needed to identify and treat HAART-eligible patients prior to severe CD4 cell decline or achievement of advanced age.

  5. Predicting hypothetical willingness to participate (WTP) in a future phase III HIV vaccine trial among high-risk adolescents.

    Science.gov (United States)

    Giocos, Georgina; Kagee, Ashraf; Swartz, Leslie

    2008-11-01

    The present study sought to determine whether the Theory of Planned Behaviour predicted stated hypothetical willingness to participate (WTP) in future Phase III HIV vaccine trials among South African adolescents. Hierarchical logistic regression analyses showed that The Theory of Planned Behaviour (TPB) significantly predicted WTP. Of all the predictors, Subjective norms significantly predicted WTP (OR = 1.19, 95% C.I. = 1.06-1.34). A stepwise logistic regression analysis revealed that Subjective Norms (OR = 1.19, 95% C.I. = 1.07-1.34) and Attitude towards participation in an HIV vaccine trial (OR = 1.32, 95% C.I. = 1.00-1.74) were significant predictors of WTP. The addition of Knowledge of HIV vaccines and HIV vaccine trials, Perceived self-risk of HIV infection, Health-promoting behaviours and Attitudes towards HIV/AIDS yielded non-significant results. These findings provide support for the Theory of Reasoned Action (TRA) and suggest that psychosocial factors may play an important role in WTP in Phase III HIV vaccine trials among adolescents.

  6. Canada's international response to HIV during times of global transition: a qualitative inquiry.

    Science.gov (United States)

    Nixon, Stephanie

    2011-04-01

    Canada's international response to HIV may be under threat given CIDA's new aid priorities that appear to exclude health. Drivers of this recent priority shift have been the influence of global aid trends among public sector donors and changes within the global HIV milieu itself. However, this is not the first time Canada has shifted in response to these two global trends. The era from 2000-2004 also witnessed dramatic changes in both the HIV field and in global thinking around international aid. As such, this article presents an evaluation of the Government of Canada's international response to HIV during the first era of transition (2000-2004) in order to derive lessons for decision-making around HIV in the current climate of change. In-depth, semi-structured interviews were conducted with 23 key informants with expertise regarding Canada's international response to HIV over time. Analysis involved multiple readings of transcripts to identify descriptive codes and establish intimacy with the data. Descriptive codes were then collapsed into thematic categories using a process of inductive reasoning. Canada's international response to HIV was perceived to be exemplary at times (e.g. seminal funding to WHO's "3-by-5" strategy), but also inconsistent (e.g., underutilized technical assistance capacity) and non-strategic (e.g., contradiction between investing in training health providers while poaching professionals to bolster Canada's workforce). Lessons from the 2000-2004 era of transition focus on strategic investments, the inextricable connection between HIV and development and strategy coherence. These results highlight that it is more constructive to ensure that Canadian development responses in all areas engage with both the upstream drivers of HIV as well as the impacts of the epidemic itself in order to achieve the greatest results from international investment and the most effective contributions to the lives of the people that these endeavours seek to

  7. Cross-reactive microbial peptides can modulate HIV-specific CD8+ T cell responses.

    Directory of Open Access Journals (Sweden)

    Christopher W Pohlmeyer

    Full Text Available Heterologous immunity is an important aspect of the adaptive immune response. We hypothesized that this process could modulate the HIV-1-specific CD8+ T cell response, which has been shown to play an important role in HIV-1 immunity and control. We found that stimulation of peripheral blood mononuclear cells (PBMCs from HIV-1-positive subjects with microbial peptides that were cross-reactive with immunodominant HIV-1 epitopes resulted in dramatic expansion of HIV-1-specific CD8+ T cells. Interestingly, the TCR repertoire of HIV-1-specific CD8+ T cells generated by ex vivo stimulation of PBMCs using HIV-1 peptide was different from that of cells stimulated with cross-reactive microbial peptides in some HIV-1-positive subjects. Despite these differences, CD8+ T cells stimulated with either HIV-1 or cross-reactive peptides effectively suppressed HIV-1 replication in autologous CD4+ T cells. These data suggest that exposure to cross-reactive microbial antigens can modulate HIV-1-specific immunity.

  8. An Increase in Religiousness/Spirituality Occurs After HIV Diagnosis and Predicts Slower Disease Progression over 4 Years in People with HIV

    Science.gov (United States)

    Ironson, Gail; Stuetzle, Rick; Fletcher, Mary Ann

    2006-01-01

    BACKGROUND Most studies on religion/spirituality predicting health outcomes have been limited to church attendance as a predictor and have focused on healthy people. However, confronting a major medical crisis may be a time when people turn to the sacred. OBJECTIVE The purpose of this study was to determine the extent to which changes in spirituality/religiousness occur after HIV diagnosis and whether changes predict disease progression. DESIGN/PARTICIPANTS This longitudinal study examined the relationship between changes in spirituality/religiousness from before with after the diagnosis of HIV, and disease progression (CD4 and viral load [VL] every 6 months) over 4 years in 100 people with HIV. Measures included change in religiousness/spirituality after diagnosis of HIV, religiousness/spirituality at various times in one’s life, church attendance, depression, hopelessness, optimism, coping (avoidant, proactive), social support, CD4/VL, and health behaviors. RESULTS Forty-five percent of the sample showed an increase in religiousness/spirituality after the diagnosis of HIV, 42% remained the same, and 13% decreased. People reporting an increase in spirituality/religiousness after the diagnosis had significantly greater preservation of CD4 cells over the 4-year period, as well as significantly better control of VL. Results were independent of (i.e., held even after controlling for) church attendance and initial disease status (CD4/VL), medication at every time point, age, gender, race, education, health behaviors (adherence, risky sex, alcohol, cocaine), depression, hopelessness, optimism, coping (avoidant, proactive), and social support. CONCLUSIONS There is an increase in spirituality/religiousness after HIV diagnosis, and this increase predicts slower disease progression; medical personnel should be aware of its potential importance. PMID:17083503

  9. Unpolarized release of vaccinia virus and HIV antigen by colchicine treatment enhances intranasal HIV antigen expression and mucosal humoral responses.

    Directory of Open Access Journals (Sweden)

    Yan Zhang

    Full Text Available The induction of a strong mucosal immune response is essential to building successful HIV vaccines. Highly attenuated recombinant HIV vaccinia virus can be administered mucosally, but even high doses of immunization have been found unable to induce strong mucosal antibody responses. In order to solve this problem, we studied the interactions of recombinant HIV vaccinia virus Tiantan strain (rVTT-gagpol in mucosal epithelial cells (specifically Caco-2 cell layers and in BALB/c mice. We evaluated the impact of this virus on HIV antigen delivery and specific immune responses. The results demonstrated that rVTT-gagpol was able to infect Caco-2 cell layers and both the nasal and lung epithelia in BALB/c mice. The progeny viruses and expressed p24 were released mainly from apical surfaces. In BALB/c mice, the infection was limited to the respiratory system and was not observed in the blood. This showed that polarized distribution limited antigen delivery into the whole body and thus limited immune response. To see if this could be improved upon, we stimulated unpolarized budding of the virus and HIV antigens by treating both Caco-2 cells and BALB/c mice with colchicine. We found that, in BALB/c mice, the degree of infection and antigen expression in the epithelia went up. As a result, specific immune responses increased correspondingly. Together, these data suggest that polarized budding limits antigen delivery and immune responses, but unpolarized distribution can increase antigen expression and delivery and thus enhance specific immune responses. This conclusion can be used to optimize mucosal HIV vaccine strategies.

  10. HIV and AIDS in South Africa: a social and moral responsibility in shaping organisational action

    Directory of Open Access Journals (Sweden)

    Renitha Rampersad

    2013-04-01

    Full Text Available In recent years, the interest in corporate social responsibility issues has shown an increase. Worldwide problems, especially those related to HIV/AIDS, caught public attention towards Corporate Social Responsibility (CSR themes. In a country with more people living with HIV/AIDS than in any other nation (UNAIDS 2007, prevention and treatment is critical. HIV/AIDS is seen to be threatening the communities in which businesses are functioning and is further threatening the business itself. This article examines the moral and social responsibility of the corporate sector in its effort to deal with the issue of HIV/AIDS. Big business leaders have recognized the threat of HIV/AIDS to the workplace and have positioned responses towards the disease from an ethical, legal and cost-effective business perspective; however the response from small to medium businesses is relatively weak. This article conveys a descriptive critique, based on bibliographic research on Corporate Social Responsibility, HIV/AIDS and related concepts.

  11. Predictive value of prostate specific antigen in a European HIV-positive cohort

    DEFF Research Database (Denmark)

    Shepherd, Leah; Borges, Álvaro H; Ravn, Lene

    2016-01-01

    BACKGROUND: It is common practice to use prostate specific antigen (PSA) ≥4.0 ng/ml as a clinical indicator for men at risk of prostate cancer (PCa), however, this is unverified in HIV+ men. We aimed to describe kinetics and predictive value of PSA for PCa in HIV+ men. METHODS: A nested case...... control study of 21 men with PCa and 40 matched-controls within EuroSIDA was conducted. Prospectively stored plasma samples before PCa (or matched date in controls) were measured for the following markers: total PSA (tPSA), free PSA (fPSA), testosterone and sex hormone binding globulin (SHBG). Conditional...... logistic regression models investigated associations between markers and PCa. Mixed models were used to describe kinetics. Sensitivity and specificity of using tPSA >4 ng/ml to predict PCa was calculated. Receiver operating characteristic curves were used to identify optimal cutoffs in HIV+ men for total...

  12. A High Frequency of HIV-Specific Circulating Follicular Helper T Cells Is Associated with Preserved Memory B Cell Responses in HIV Controllers.

    Science.gov (United States)

    Claireaux, M; Galperin, M; Benati, D; Nouël, A; Mukhopadhyay, M; Klingler, J; de Truchis, P; Zucman, D; Hendou, S; Boufassa, F; Moog, C; Lambotte, O; Chakrabarti, L A

    2018-05-08

    Follicular helper T cells (Tfh) play an essential role in the affinity maturation of the antibody response by providing help to B cells. To determine whether this CD4 + T cell subset may contribute to the spontaneous control of HIV infection, we analyzed the phenotype and function of circulating Tfh (cTfh) in patients from the ANRS CO21 CODEX cohort who naturally controlled HIV-1 replication to undetectable levels and compared them to treated patients with similarly low viral loads. HIV-specific cTfh (Tet + ), detected by Gag-major histocompatibility complex class II (MHC-II) tetramer labeling in the CD45RA - CXCR5 + CD4 + T cell population, proved more frequent in the controller group ( P = 0.002). The frequency of PD-1 expression in Tet + cTfh was increased in both groups (median, >75%) compared to total cTfh (<30%), but the intensity of PD-1 expression per cell remained higher in the treated patient group ( P = 0.02), pointing to the persistence of abnormal immune activation in treated patients. The function of cTfh, analyzed by the capacity to promote IgG secretion in cocultures with autologous memory B cells, did not show major differences between groups in terms of total IgG production but proved significantly more efficient in the controller group when measuring HIV-specific IgG production. The frequency of Tet + cTfh correlated with HIV-specific IgG production ( R = 0.71 for Gag-specific and R = 0.79 for Env-specific IgG, respectively). Taken together, our findings indicate that key cTfh-B cell interactions are preserved in controlled HIV infection, resulting in potent memory B cell responses that may play an underappreciated role in HIV control. IMPORTANCE The rare patients who spontaneously control HIV replication in the absence of therapy provide a unique model to identify determinants of an effective anti-HIV immune response. HIV controllers show signs of particularly efficient antiviral T cell responses, while their humoral response was until recently

  13. Specificity and polyreactivity of the antibody response during natural HIV-1 infection

    OpenAIRE

    Wang, Xin

    2006-01-01

    The specificity and polyreactivity of the antibody response in natural HIV-1 infection were studied. First, to investigate the overall antibody response, overlapping linear peptides were used to screen sera taken from HIV-1-infected individuals. The polyclonal antibody response was relatively stable during long-term infection, compared with acute infection, and mostly directed against immunodominant regions. Low level, transient antibody responses were detected against membrane proximal exter...

  14. Responsibility as a dimension of HIV prevention normative beliefs: measurement in three drug-using samples.

    Science.gov (United States)

    Ross, M W; Timpson, S C; Williams, M L; Amos, C; McCurdy, S; Bowen, A M; Kilonzo, G P

    2007-03-01

    The concept of responsibility was derived originally from principles of morality, as part of a network of rights, duties and obligations. HIV risk-related studies have suggested that a sense of responsibility for condom use to protect a partner is a potentially important predictor of condom use in drug-using populations. We created a four-item scale measuring Self responsibility to use condoms and Partner's responsibility to use condoms. Data were collected from three drug-using samples: crack smokers, HIV seropositive crack smokers in an intervention study in Houston, Texas, and Tanzanian heroin users in Dar es Salaam. Data indicated that the four responsibility items had high alpha coefficients in each sample, and that there were moderate to high intercorrelations between equivalent self and partner responsibility items. There were significant differences in scale scores between the crack smokers and the HIV positive crack smokers and the Tanzanian samples, but no significant differences between the HIV positive and Tanzanian samples. Comparing within the first crack-smoker sample those who were HIV positive and negative showed significant differences in the direction of higher beliefs in responsibility to use condoms in the HIV positive group. These data suggest that responsibility is measurable, holds similar psychometric properties across three samples differing in culture and HIV serostatus, and that condom use responsibility is conceptualized as a measure of general responsibility rather than as a reciprocal self/partner responsibility.

  15. Pharmaceutical industry's corporate social responsibility towards HIV/AIDS.

    Science.gov (United States)

    Khanna, Arun Kumar

    2006-01-01

    The pharmaceutical industry has a corporate social responsibility (CSR) towards HIV/AIDS. Measures taken to increase awareness of HIV/AIDS, availability and accessibility of potent and patient-friendly FDCs / Kits for adults and children will go a long way in increasing awareness and acceptance of this disease and its therapy. This will improve adherence, lower resistance and facilitate better disease management. This article discusses some of the CSR initiatives and their scope.

  16. Building a durable response to HIV/AIDS: implications for health systems.

    Science.gov (United States)

    Atun, Rifat; Bataringaya, Jacqueline

    2011-08-01

    The remarkable rise in investments for HIV control programs in 2003-2010 enabled an unprecedented expansion of access to HIV services in low-income and middle-income countries. By the end of 2010, more than 5.2 million people were receiving antiretroviral therapy (ART), which transformed HIV infection, once a death sentence, into a long-term illness. The rapid expansion in the number of persons receiving ART means that health systems must continue to provide acute life-saving care for those with advanced HIV/AIDS although also providing chronic care services to expanding cohorts of more stable patients who are doing well on ART. This expansion also means a transition from an emergency response to the epidemic, characterized by a public health approach, to a more integrated and durable approach to HIV prevention, care, and treatment services that fosters individualized care for those requiring long-term antiretroviral treatment. Yet most low-income and middle-income countries, which have weak health systems, are poorly prepared to make this transition. In this article, we highlight the challenges health systems face in developing a sustained and durable response to HIV/AIDS. The article analyses the readiness of health systems to combine rapid expansion of ART access with long-term treatment and continuity of care for a growing cohort of patients. We argue that effective management of a transition from an emergency AIDS response to long-term programatic strategies will require a paradigm shift that enables leveraging investments in HIV to build sustainable health systems for managing large cohorts of patients receiving ART although meeting the immediate needs of those who remain without access to HIV treatment and care.

  17. Prediction of week 4 virological response in hepatitis C for making decision on triple therapy: the Optim study.

    Directory of Open Access Journals (Sweden)

    Manuel Romero-Gómez

    Full Text Available Virological response to peginterferon + ribavirin (P+R at week 4 can predict sustained virological response (SVR. While patients with rapid virological response (RVR do not require triple therapy, patients with a decline <1 log10 IU/ml HCVRNA (D1L should have treatment discontinued due to low SVR rate.To develop a tool to predict first 4 weeks' viral response in patients with hepatitis C genotype 1&4 treated with P+R.In this prospective and multicenter study, HCV mono-infected (n=538 and HCV/HIV co-infected (n=186 patients were included. To develop and validate a prognostic tool to detect RVR and D1L, we segregated the patients as an estimation cohort (to construct the model and a validation cohort (to validate the model.D1L was reached in 509 (80.2% and RVR in 148 (22.5% patients. Multivariate analyses demonstrated that HIV co-infection, Forns' index, LVL, IL28B-CC and Genotype-1 were independently related to RVR as well as D1L. Diagnostic accuracy (AUROC for D1L was: 0.81 (95%CI: 0.76 ̶ 0.86 in the estimation cohort and 0.71 (95%CI: 0.62 ̶ 0.79 in the validation cohort; RVR prediction: AUROC 0.83 (95%CI: 0.78 ̶ 0.88 in the estimation cohort and 0.82 (95%CI: 0.76 ̶ 0.88 in the validation cohort. Cost-analysis of standard 48-week treatment indicated a saving of 30.3% if the prognostic tool is implemented.The combination of genetic (IL28B polymorphism and viral genotype together with viral load, HIV co-infection and fibrosis stage defined a tool able to predict RVR and D1L at week 4. Using this tool would be a cost-saving strategy compared to universal triple therapy for hepatitis C.

  18. Sex Behaviour Change in Response to the HIV/AIDS Threat among ...

    African Journals Online (AJOL)

    Sex Behaviour Change in Response to the HIV/AIDS Threat among University ... active, and prior studies have documented an appreciable knowledge of the HIV ... Design: A cross sectional descriptive survey of selfreported sexual behaviour ...

  19. Mobilisation, politics, investment and constant adaptation: lessons from the Australian health-promotion response to HIV.

    Science.gov (United States)

    Brown, Graham; O'Donnell, Daryl; Crooks, Levinia; Lake, Rob

    2014-04-01

    The Australian response to HIV oversaw one of the most rapid and sustained changes in community behaviour in Australia's health-promotion history. The combined action of communities of gay men, sex workers, people who inject drugs, people living with HIV and clinicians working in partnership with government, public health and research has been recognised for many years as highly successful in minimising the HIV epidemic. This article will show how the Australian HIV partnership response moved from a crisis response to a constant and continuously adapting response, with challenges in sustaining the partnership. Drawing on key themes, lessons for broader health promotion are identified. The Australian HIV response has shown that a partnership that is engaged, politically active, adaptive and resourced to work across multiple social, structural, behavioural and health-service levels can reduce the transmission and impact of HIV. The experience of the response to HIV, including its successes and failures, has lessons applicable across health promotion. This includes the need to harness community mobilisation and action; sustain participation, investment and leadership across the partnership; commit to social, political and structural approaches; and build and use evidence from multiple sources to continuously adapt and evolve. So what? The Australian HIV response was one of the first health issues to have the Ottawa Charter embedded from the beginning, and has many lessons to offer broader health promotion and common challenges. As a profession and a movement, health promotion needs to engage with the interactions and synergies across the promotion of health, learn from our evidence, and resist the siloing of our responses.

  20. Mucosal IgA Responses: Damaged in Established HIV Infection—Yet, Effective Weapon against HIV Transmission

    Directory of Open Access Journals (Sweden)

    Viraj Kulkarni

    2017-11-01

    Full Text Available HIV infection not only destroys CD4+ T cells but also inflicts serious damage to the B-cell compartment, such as lymphadenopathy, destruction of normal B-cell follicle architecture, polyclonal hypergammaglobulinemia, increased apoptosis of B cells, and irreversible loss of memory B-cell responses with advanced HIV disease. Subepithelial B cells and plasma cells are also affected, which results in loss of mucosal IgG and IgA antibodies. This leaves the mucosal barrier vulnerable to bacterial translocation. The ensuing immune activation in mucosal tissues adds fuel to the fire of local HIV replication. We postulate that compromised mucosal antibody defenses also facilitate superinfection of HIV-positive individuals with new HIV strains. This in turn sets the stage for the generation of circulating recombinant forms of HIV. What can the mucosal B-cell compartment contribute to protect a healthy, uninfected host against mucosal HIV transmission? Here, we discuss proof-of-principle studies we have performed using passive mucosal immunization, i.e., topical administration of preformed anti-HIV monoclonal antibodies (mAbs as IgG1, dimeric IgA1 (dIgA1, and dIgA2 isotypes, alone or in combination. Our data indicate that mucosally applied anti-HIV envelope mAbs can provide potent protection against mucosal transmission of simian-human immunodeficiency virus. Our review also discusses the induction of mucosal antibody defenses by active vaccination and potential strategies to interrupt the vicious cycle of bacterial translocation, immune activation, and stimulation of HIV replication in individuals with damaged mucosal barriers.

  1. Broad and potent immune responses to a low dose intradermal HIV-1 DNA boosted with HIV-1 recombinant MVA among healthy adults in Tanzania☆,☆☆

    Science.gov (United States)

    Bakari, Muhammad; Aboud, Said; Nilsson, Charlotta; Francis, Joel; Buma, Deus; Moshiro, Candida; Aris, Eric A.; Lyamuya, Eligius F.; Janabi, Mohamed; Godoy-Ramirez, Karina; Joachim, Agricola; Polonis, Victoria R.; Bråve, Andreas; Earl, Patricia; Robb, Merlin; Marovich, Mary; Wahren, Britta; Pallangyo, Kisali; Biberfeld, Gunnel; Mhalu, Fred; Sandström, Eric

    2016-01-01

    Background We conducted a phase I/II randomized placebo-controlled trial with the aim of exploring whether priming with a low intradermal dose of a multiclade, multigene HIV-1 DNA vaccine could improve the immunogenicity of the same vaccine given intramuscularly prior to boosting with a heterologous HIV-1 MVA among healthy adults in Dar es Salaam, Tanzania. Methods Sixty HIV-uninfected volunteers were randomized to receive DNA plasmid vaccine 1 mg intradermally (id), n = 20, or 3.8 mg intramuscularly (im), n = 20, or placebo, n = 20, using a needle-free injection device. DNA plasmids encoding HIV-1 genes gp160 subtype A, B, C; rev B; p17/p24 gag A, B and Rtmut B were given at weeks 0, 4 and 12. Recombinant MVA (108 pfu) expressing HIV-1 Env, Gag, Pol of CRF01_AE or placebo was administered im at month 9 and 21. Results The vaccines were well tolerated. Two weeks after the third HIV-DNA injection, 22/38 (58%) vaccinees had IFN-γ ELISpot responses to Gag. Two weeks after the first HIV-MVA boost all 35 (100%) vaccinees responded to Gag and 31 (89%) to Env. Two to four weeks after the second HIV-MVA boost, 28/29 (97%) vaccinees had IFN-γ ELISpot responses, 27 (93%) to Gag and 23 (79%) to Env. The id-primed recipients had significantly higher responses to Env than im recipients. Intracellular cytokine staining for Gag-specific IFN-γ/IL-2 production showed both CD8+ and CD4+ T cell responses. All vaccinees had HIV-specific lymphoproliferative responses. All vaccinees reacted in diagnostic HIV serological tests and 26/29 (90%) had antibodies against gp160 after the second HIV-MVA boost. Furthermore, while all of 29 vaccinee sera were negative for neutralizing antibodies against clade B, C and CRF01 AE pseudoviruses in the TZM-bl neutralization assay, in a PBMC assay, the response rate ranged from 31% to 83% positives, depending upon the clade B or CRF01_AE virus tested. This vaccine approach is safe and highly immunogenic. Low dose, id HIV-DNA priming elicited higher

  2. An updated prediction model of the global risk of cardiovascular disease in HIV-positive persons

    DEFF Research Database (Denmark)

    Friis-Møller, Nina; Ryom, Lene; Smith, Colette

    2016-01-01

    ,663 HIV-positive persons from 20 countries in Europe and Australia, who were free of CVD at entry into the Data-collection on Adverse Effects of Anti-HIV Drugs (D:A:D) study. Cox regression models (full and reduced) were developed that predict the risk of a global CVD endpoint. The predictive performance...... significantly predicted risk more accurately than the recalibrated Framingham model (Harrell's c-statistic of 0.791, 0.783 and 0.766 for the D:A:D full, D:A:D reduced, and Framingham models respectively; p models also more accurately predicted five-year CVD-risk for key prognostic subgroups...... to quantify risk and to guide preventive care....

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

    Science.gov (United States)

    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.

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

    Directory of Open Access Journals (Sweden)

    María Julia Ruiz

    2017-12-01

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

  5. Risk factors for discordant immune response among HIV-infected ...

    African Journals Online (AJOL)

    Risk factors for discordant immune response among HIV-infected patients initiating antiretroviral therapy: A retrospective cohort study. ... Multivariate logistic regression models were used to estimate adjusted odds ratios (AORs) to determine associations between discordant immune response and clinical and demographic ...

  6. HIV/AIDS response in Rivers State, Nigeria: an evaluation of ...

    African Journals Online (AJOL)

    Background: Over the years Rivers State of Nigeria has witnessed a rising trend in HIV/AIDS infection. In 2006, the State Action Committee on AIDS commenced the implementation of a Strategic Response Plan to prevent and mitigate the effect of HIV/AIDS by 2009. Aim : To verify the extent of achievement of the Strategic ...

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

    Directory of Open Access Journals (Sweden)

    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.

  8. Predicting HIV-1 transmission and antibody neutralization efficacy in vivo from stoichiometric parameters.

    Directory of Open Access Journals (Sweden)

    Oliver F Brandenberg

    2017-05-01

    Full Text Available The potential of broadly neutralizing antibodies targeting the HIV-1 envelope trimer to prevent HIV-1 transmission has opened new avenues for therapies and vaccines. However, their implementation remains challenging and would profit from a deepened mechanistic understanding of HIV-antibody interactions and the mucosal transmission process. In this study we experimentally determined stoichiometric parameters of the HIV-1 trimer-antibody interaction, confirming that binding of one antibody is sufficient for trimer neutralization. This defines numerical requirements for HIV-1 virion neutralization and thereby enables mathematical modelling of in vitro and in vivo antibody neutralization efficacy. The model we developed accurately predicts antibody efficacy in animal passive immunization studies and provides estimates for protective mucosal antibody concentrations. Furthermore, we derive estimates of the probability for a single virion to start host infection and the risks of male-to-female HIV-1 transmission per sexual intercourse. Our work thereby delivers comprehensive quantitative insights into both the molecular principles governing HIV-antibody interactions and the initial steps of mucosal HIV-1 transmission. These insights, alongside the underlying, adaptable modelling framework presented here, will be valuable for supporting in silico pre-trial planning and post-hoc evaluation of HIV-1 vaccination or antibody treatment trials.

  9. Bacterial vaginosis, human papilloma virus and herpes viridae do not predict vaginal HIV RNA shedding in women living with HIV in Denmark

    DEFF Research Database (Denmark)

    Wessman, Maria; Thorsteinsson, Kristina; Jensen, Jørgen S

    2017-01-01

    in the genital tract despite undetectable HIV RNA plasma viral load. We examined the prevalence and diagnostic predictors of BV and HIV-1 RNA vaginal shedding in women living with HIV (WLWH) in Denmark, taking into account the presence of human papillomavirus (HPV) and herpes viridae. METHODS: WLWH between 18......-51 years were recruited from six Departments of Infectious Diseases in Denmark during enrolment in the SHADE cohort; a prospective cohort study of WLWH attending regular outpatient care. BV was diagnosed by microscopy of vaginal swabs and PCR was used for detection of BV-associated bacteria, HPV, herpes...... RNA. Both before and after adjustment for BV, age, ethnicity, plasma HIV RNA, CD4 cell count, herpes viridae and HPV, we found no significant predictors of HIV RNA vaginal shedding. CONCLUSION: In well-treated WLWH, BV, herpes viridae or HPV do not predict vaginal HIV RNA shedding. This implies...

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

    Directory of Open Access Journals (Sweden)

    Nesrina eImami

    2013-03-01

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

  11. 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

  12. Syphilis and HIV-1 co-infection: influence on CD4 T cell count, HIV-1 viral load and treatment response

    DEFF Research Database (Denmark)

    Kofoed, Kristian; Gerstoft, Jan; Mathiesen, Lars Reinhardt

    2006-01-01

    OBJECTIVES: To assess the effect of human immunodeficiency virus (HIV)-1 and syphilis coinfection on HIV-ribonucleic acid (RNA) viral load, CD4 cell count, and the response in rapid plasmin reagin (RPR) to treatment of the syphilis infection. STUDY DESIGN: Cases of syphilis diagnosed during 1 year...... in HIV-infected patients in Copenhagen were included. HIV-RNA, CD4 cell counts, and RPR-serology were measured before, during, and after syphilis. RESULTS: Forty-one patients were included. CD4 cell count decreased significantly during infection in patients with primary and secondary stages of syphilis...... (mean 106 cells/mm, P = 0.03). Treatment of syphilis was associated with an increase in the CD4 cell count and a decrease in HIV-RNA in the overall group (mean 66 cells/mm and -0.261 RNA log10 copies/ml, P = 0.02 and 0.04). The serological response rates for 15 patients treated with penicillin and 25...

  13. Boosting of HIV-1 neutralizing antibody responses by a distally related retroviral envelope protein.

    Science.gov (United States)

    Uchtenhagen, Hannes; Schiffner, Torben; Bowles, Emma; Heyndrickx, Leo; LaBranche, Celia; Applequist, Steven E; Jansson, Marianne; De Silva, Thushan; Back, Jaap Willem; Achour, Adnane; Scarlatti, Gabriella; Fomsgaard, Anders; Montefiori, David; Stewart-Jones, Guillaume; Spetz, Anna-Lena

    2014-06-15

    Our knowledge of the binding sites for neutralizing Abs (NAb) that recognize a broad range of HIV-1 strains (bNAb) has substantially increased in recent years. However, gaps remain in our understanding of how to focus B cell responses to vulnerable conserved sites within the HIV-1 envelope glycoprotein (Env). In this article, we report an immunization strategy composed of a trivalent HIV-1 (clade B envs) DNA prime, followed by a SIVmac239 gp140 Env protein boost that aimed to focus the immune response to structurally conserved parts of the HIV-1 and simian immunodeficiency virus (SIV) Envs. Heterologous NAb titers, primarily to tier 1 HIV-1 isolates, elicited during the trivalent HIV-1 env prime, were significantly increased by the SIVmac239 gp140 protein boost in rabbits. Epitope mapping of Ab-binding reactivity revealed preferential recognition of the C1, C2, V2, V3, and V5 regions. These results provide a proof of concept that a distally related retroviral SIV Env protein boost can increase pre-existing NAb responses against HIV-1. Copyright © 2014 by The American Association of Immunologists, Inc.

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

    Science.gov (United States)

    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

  15. How Do Social Capital and HIV/AIDS Outcomes Geographically Cluster and Which Sociocontextual Mechanisms Predict Differences Across Clusters?

    Science.gov (United States)

    Ransome, Yusuf; Dean, Lorraine T; Crawford, Natalie D; Metzger, David S; Blank, Michael B; Nunn, Amy S

    2017-09-01

    Place of residence has been associated with HIV transmission risks. Social capital, defined as features of social organization that improve efficiency of society by facilitating coordinated actions, often varies by neighborhood, and hypothesized to have protective effects on HIV care continuum outcomes. We examined whether the association between social capital and 2 HIV care continuum outcomes clustered geographically and whether sociocontextual mechanisms predict differences across clusters. Bivariate Local Moran's I evaluated geographical clustering in the association between social capital (participation in civic and social organizations, 2006, 2008, 2010) and [5-year (2007-2011) prevalence of late HIV diagnosis and linkage to HIV care] across Philadelphia, PA, census tracts (N = 378). Maps documented the clusters and multinomial regression assessed which sociocontextual mechanisms (eg, racial composition) predict differences across clusters. We identified 4 significant clusters (high social capital-high HIV/AIDS, low social capital-low HIV/AIDS, low social capital-high HIV/AIDS, and high social capital-low HIV/AIDS). Moran's I between social capital and late HIV diagnosis was (I = 0.19, z = 9.54, P social capital was lowest and HIV burden the highest, compared with clusters with high social capital and lowest HIV burden. The association between social participation and HIV care continuum outcomes cluster geographically in Philadelphia, PA. HIV prevention interventions should account for this phenomenon. Reducing geographic disparities will require interventions tailored to each continuum step and that address socioeconomic factors such as neighborhood median income.

  16. Designing Peptide-Based HIV Vaccine for Chinese

    Science.gov (United States)

    Fan, Xiaojuan

    2014-01-01

    CD4+ T cells are central to the induction and maintenance of CD8+ T cell and antibody-producing B cell responses, and the latter are essential for the protection against disease in subjects with HIV infection. How to elicit HIV-specific CD4+ T cell responses in a given population using vaccines is one of the major areas of current HIV vaccine research. To design vaccine that targets specifically Chinese, we assembled a database that is comprised of sequences from 821 Chinese HIV isolates and 46 human leukocyte antigen (HLA) DR alleles identified in Chinese population. We then predicted 20 potential HIV epitopes using bioinformatics approaches. The combination of these 20 epitopes has a theoretical coverage of 98.1% of the population for both the prevalent HIV genotypes and also Chinese HLA-DR types. We suggest that testing this vaccine experimentally will facilitate the development of a CD4+ T cell vaccine especially catered for Chinese. PMID:25136573

  17. HIV-specific antibodies but not t-cell responses are associated with protection in seronegative partners of HIV-1-infected individuals in Cambodia.

    Science.gov (United States)

    Nguyen, Marie; Pean, Polidy; Lopalco, Lucia; Nouhin, Janin; Phoung, Viseth; Ly, Nary; Vermisse, Pierre; Henin, Yvette; Barré-Sinoussi, Françoise; Burastero, Samuele E; Reynes, Jean-Marc; Carcelain, Guislaine; Pancino, Gianfranco

    2006-08-01

    To study biological factors related to protection against HIV-1 infection in Cambodia, we recruited 48 partners of HIV-1-infected patients who remained uninfected (exposed uninfected individuals, EUs) despite unprotected sexual intercourse for more than 1 year and 49 unexposed controls (UCs). HIV-1-specific antibodies (IgA anti-gp41 and IgG anti-CD4-gp120 complex), T-cell responses, and cellular factors that may be involved in protection (peripheral blood mononuclear cell [PBMC] resistance to HIV-1 infection and beta-chemokine production) were evaluated. Anti-HIV-1 antibodies were higher in EUs than those in UCs (P = 0.01 and P = 0.04 for anti-gp41 and anti-CD4-gp120, respectively). We observed a decreased susceptibility to a primary Cambodian isolate, HIV-1KH019, in EU PBMCs as compared with UC PBMCs (P = 0.03). A weak T-cell response to one pool of HIV-1 Gag peptides was found by ELISpot in 1 of 19 EUs. Whereas T-cell specific immunity was not associated to protection, our results suggest that HIV-specific humoral immunity and reduced cell susceptibility to infection may contribute to protection against HIV-1 infection in Cambodian EUs.

  18. Integrated response toward HIV: a health promotion case study from China.

    Science.gov (United States)

    Jiang, Zhen; Wang, Debin; Yang, Sen; Duan, Mingyue; Bu, Pengbin; Green, Andrew; Zhang, Xuejun

    2011-06-01

    Integrated HIV response refers to a formalized, collaborative process among organizations in communities with HIV at-risk populations. It is a both comprehensive and flexible scheme, which may include community-based environment promotion, skill coalition, fund linkage, human resource collaboration and service system jointly for both HIV prevention and control. It enables decisions and actions responds over time. In 1997, the Chinese government developed a 10-year HIV project supported by World Bank Loan (H9-HIV/AIDS/STIs). It was the first integrated STI/HIV intervention project in China and provides a unique opportunity to explore the long-term comprehensive STI/HIV intervention in a low-middle income country setting. Significant outcomes were identified as development and promotion of the national strategic plan and its ongoing implementation; positive knowledge, behavioral and STI/HIV prevalence rate change; and valuable experiences for managing integrated HIV/STI intervention projects. Essential factors for the success of the project and the key tasks for the next step were identified and included well-designed intervention in rural and low economic regions, unified program evaluation framework and real-time information collection and assessment.

  19. Modelling sexual transmission of HIV: testing the assumptions, validating the predictions

    Science.gov (United States)

    Baggaley, Rebecca F.; Fraser, Christophe

    2010-01-01

    Purpose of review To discuss the role of mathematical models of sexual transmission of HIV: the methods used and their impact. Recent findings We use mathematical modelling of “universal test and treat” as a case study to illustrate wider issues relevant to all modelling of sexual HIV transmission. Summary Mathematical models are used extensively in HIV epidemiology to deduce the logical conclusions arising from one or more sets of assumptions. Simple models lead to broad qualitative understanding, while complex models can encode more realistic assumptions and thus be used for predictive or operational purposes. An overreliance on model analysis where assumptions are untested and input parameters cannot be estimated should be avoided. Simple models providing bold assertions have provided compelling arguments in recent public health policy, but may not adequately reflect the uncertainty inherent in the analysis. PMID:20543600

  20. Immunoregulatory activities of human immunodeficiency virus (HIV) proteins: Effect of HIV recombinant and synthetic peptides on immunoglobulin synthesis and proliferative responses by normal lymphocytes

    International Nuclear Information System (INIS)

    Nair, M.P.N.; Pottathil, R.; Heimer, E.P.; Schwartz, S.A.

    1988-01-01

    Recombinant and synthetic peptides corresponding to envelope proteins of the human immunodeficiency virus (HIV) were examined for their effects on the activities of lymphocytes from normal donors in vitro. Although lymphocytes cultured with env-gag peptides produced significant amounts of IgG, addition of env-gag peptides to a pokeweed mitogen-induced B-cell activation system resulted in suppression of immunoglobulin synthesis by normal lymphocytes. Recombinant antigens, env-gag and env-80 dihydrofolate reductase (DHFR), produced a substantial proliferative response by peripheral blood mononuclear cells (PBMC) as determined by [ 3 H]thymidine incorporation. PBMC precultured with HIV synthetic peptide env 578-608 also manifested significant proliferative responses as compared to control cultures. CD3 + lymphocytes precultured with recombinant HIV antigens, env-gag and env-80 DHFR, and synthetic HIV peptide, env 487-511, showed moderate but significant proliferative responses. Both recombinant antigens and synthetic peptides also produced a dose-dependent stimulatory effect on proliferation by CD3 - lymphocytes. These studies demonstrate that recombinant and synthetic peptides of the HIV genome express immunoregulatory T- and B-cell epitopes. Identification of unique HIV epitopes with immunogenic and immunoregulatory activities is necessary for the development of an effective vaccine against HIV infection

  1. Bacterial vaginosis, human papilloma virus and herpes viridae do not predict vaginal HIV RNA shedding in women living with HIV in Denmark.

    Science.gov (United States)

    Wessman, Maria; Thorsteinsson, Kristina; Jensen, Jørgen S; Storgaard, Merete; Rönsholt, Frederikke F; Johansen, Isik S; Pedersen, Gitte; Nørregård Nielsen, Lars; Bonde, Jesper; Katzenstein, Terese L; Weis, Nina; Lebech, Anne-Mette

    2017-05-31

    Bacterial vaginosis (BV) has been found to be associated with HIV acquisition and transmission. This is suggested to be due to higher HIV RNA levels in cervicovaginal fluids in women living with HIV (WLWH) with BV, as bacteria associated with BV may induce viral replication and shedding in the genital tract despite undetectable HIV RNA plasma viral load. We examined the prevalence and diagnostic predictors of BV and HIV-1 RNA vaginal shedding in women living with HIV (WLWH) in Denmark, taking into account the presence of human papillomavirus (HPV) and herpes viridae. WLWH between 18-51 years were recruited from six Departments of Infectious Diseases in Denmark during enrolment in the SHADE cohort; a prospective cohort study of WLWH attending regular outpatient care. BV was diagnosed by microscopy of vaginal swabs and PCR was used for detection of BV-associated bacteria, HPV, herpes viridae, and vaginal HIV viral load. Median age of the 150 included women was 41 years; ethnicity was predominantly White (35%) or Black (47%). The majority (96%) was on ART and had undetectable (85%) plasma HIV RNA (<40 copies/mL). BV was diagnosed in 32%. Overall, 11% had detectable vaginal HIV RNA. Both before and after adjustment for BV, age, ethnicity, plasma HIV RNA, CD4 cell count, herpes viridae and HPV, we found no significant predictors of HIV RNA vaginal shedding. In well-treated WLWH, BV, herpes viridae or HPV do not predict vaginal HIV RNA shedding. This implies that HIV shedding does not seem to be increased by BV.

  2. Educational attainment and risk of HIV infection, response to antiretroviral treatment, and mortality in HIV-infected patients

    DEFF Research Database (Denmark)

    Legarth, Rebecca; Omland, Lars H; Kronborg, Gitte

    2014-01-01

    .0 (95% CI 1.2-3.4) for population controls with low educational attainment compared with medium and high educational attainment. CONCLUSION: With free and equal access to healthcare, low educational attainment might increase risk of HIV infection among heterosexual individuals, but was not associated......OBJECTIVE: To estimate association between educational attainment and risk of HIV diagnosis, response to HAART, all-cause, and cause-specific mortality in Denmark in 1998-2009. DESIGN: Prospective, population-based cohort study including 1277 incident HIV-infected patients without hepatitis C virus...... or intravenous drug abuse identified in the Danish HIV Cohort Study and 5108 individually matched population controls. METHODS: Data on educational attainment, categorized as low, medium, or high, were identified in The Danish Attainment Register. Logistic and Poisson regression were used to estimate odds ratios...

  3. Liver stiffness is not associated with short- and long-term plasma HIV RNA replication in immunocompetent patients with HIV infection and with HIV/HCV coinfection

    Science.gov (United States)

    Parisi, Saverio Giuseppe; Basso, Monica; Mengoli, Carlo; Scaggiante, Renzo; Andreis, Samantha; Franzetti, Marzia Maria; Cattelan, Anna Maria; Zago, Daniela; Cruciani, Mario; Andreoni, Massimo; Piovesan, Sara; Palù, Giorgio; Alberti, Alfredo

    2017-01-01

    Background Human immunodeficiency virus (HIV) may be directly responsible for liver damage but there are contrasting data regarding the influence of detectable plasma viremia. We analyzed the influence of plasma HIV RNA (pHIV) detectability and of other clinical and viro-immunological variables on liver stiffness (LS) measurement in adult immunocompetent HIV-monoinfected patients and in patients coinfected with hepatitis C virus (HCV). Methods Logistic regression analysis was performed using the value of LS>7.1 kPa as the dependent variable. A linear regression model was applied using LS measurement after log10 transformation (lkpa) as the dependent variable and we analyzed the predicted values versus the observed lkpa values; pHIV was classified as detectable or undetectable in the 12- and 36-month study periods before LS measurement. Results We studied 251 patients (178 with HIV monoinfection), most of whom were on antiviral treatment; 36-month study time was available for 154 subjects. The mean CD4+ cell count was 634 cells/mm3 in HIV-monoinfected patients and 606 cells/mm3 in coinfected patients. No difference in LS was found between patients with detectable or undetectable pHIV in either the 12- or the 36-month study period before transient elastography. The mean LS was higher in HIV/HCV coinfected patients (P<0.0001) than in the HIV-monoinfected subjects; lkpa was positively correlated with HCV coinfection (P<0.0001) and aspartate aminotransferase levels (P<0.0001). Detectable pHIV failed to reach significance. Eight HIV-monoinfected patients had a predicted LS measurement lower than the observed one, while eight patients had the opposite result. Conclusion LS was not correlated with ongoing HIV replication during the 12- and 36-month study periods in immunocompetent HIV-monoinfected and HIV/HCV-coinfected patients. PMID:28845109

  4. HIV and injecting drug use in Indonesia: epidemiology and national response.

    Science.gov (United States)

    Afriandi, Irvan; Aditama, Tjandra Yoga; Mustikawati, Dyah; Oktavia, Martiani; Alisjahbana, Bachti; Riono, Pandu

    2009-07-01

    Indonesia is facing one of the most rapidly growing HIV-epidemics in Asia. Risk behaviour associated with injecting drug use, such as sharing contaminated needles, is the main risk factor for HIV infection. Among the general population the prevalence of HIV-infection is still low (0.2%), but up to 50% or more of the estimated 145.000 - 170.000 injecting drug users are already HIV-positive. Overrepresentation of injecting drug users and continued risk behavior inside Indonesian prisons contribute to spread of HIV. Through sexual contacts, HIV is transmitted from current or previous injecting drug users to their non-injecting sexual partners; 10-20% of this group may already be infected. The national response targeted to limit spread of HIV through injecting drug use has included needle and syringe program (NSP), methadone maintenance treatment (MMT), voluntary counseling and testing (VCT), and outreach program as priority programs. However coverage and utilization of the harm reduction services is still limited, but effective integration with HIV testing and treatment is expanding. By 2008, there were 110 service points for NSP and 24 operational MMT clinics. Nevertheless, utilization of these services has been less satisfactory and their effectiveness has been questioned. Besides effective prevention, HIV- testing and earlier treatment of HIV-seropositve individuals, including those with a history of injecting drug use, will help control the growing HIV-epidemic in Indonesia.

  5. Accounting for False Positive HIV Tests: Is Visceral Leishmaniasis Responsible?

    Science.gov (United States)

    Shanks, Leslie; Ritmeijer, Koert; Piriou, Erwan; Siddiqui, M Ruby; Kliescikova, Jarmila; Pearce, Neil; Ariti, Cono; Muluneh, Libsework; Masiga, Johnson; Abebe, Almaz

    2015-01-01

    Co-infection with HIV and visceral leishmaniasis is an important consideration in treatment of either disease in endemic areas. Diagnosis of HIV in resource-limited settings relies on rapid diagnostic tests used together in an algorithm. A limitation of the HIV diagnostic algorithm is that it is vulnerable to falsely positive reactions due to cross reactivity. It has been postulated that visceral leishmaniasis (VL) infection can increase this risk of false positive HIV results. This cross sectional study compared the risk of false positive HIV results in VL patients with non-VL individuals. Participants were recruited from 2 sites in Ethiopia. The Ethiopian algorithm of a tiebreaker using 3 rapid diagnostic tests (RDTs) was used to test for HIV. The gold standard test was the Western Blot, with indeterminate results resolved by PCR testing. Every RDT screen positive individual was included for testing with the gold standard along with 10% of all negatives. The final analysis included 89 VL and 405 non-VL patients. HIV prevalence was found to be 12.8% (47/ 367) in the VL group compared to 7.9% (200/2526) in the non-VL group. The RDT algorithm in the VL group yielded 47 positives, 4 false positives, and 38 negatives. The same algorithm for those without VL had 200 positives, 14 false positives, and 191 negatives. Specificity and positive predictive value for the group with VL was less than the non-VL group; however, the difference was not found to be significant (p = 0.52 and p = 0.76, respectively). The test algorithm yielded a high number of HIV false positive results. However, we were unable to demonstrate a significant difference between groups with and without VL disease. This suggests that the presence of endemic visceral leishmaniasis alone cannot account for the high number of false positive HIV results in our study.

  6. Accounting for False Positive HIV Tests: Is Visceral Leishmaniasis Responsible?

    Directory of Open Access Journals (Sweden)

    Leslie Shanks

    Full Text Available Co-infection with HIV and visceral leishmaniasis is an important consideration in treatment of either disease in endemic areas. Diagnosis of HIV in resource-limited settings relies on rapid diagnostic tests used together in an algorithm. A limitation of the HIV diagnostic algorithm is that it is vulnerable to falsely positive reactions due to cross reactivity. It has been postulated that visceral leishmaniasis (VL infection can increase this risk of false positive HIV results. This cross sectional study compared the risk of false positive HIV results in VL patients with non-VL individuals.Participants were recruited from 2 sites in Ethiopia. The Ethiopian algorithm of a tiebreaker using 3 rapid diagnostic tests (RDTs was used to test for HIV. The gold standard test was the Western Blot, with indeterminate results resolved by PCR testing. Every RDT screen positive individual was included for testing with the gold standard along with 10% of all negatives. The final analysis included 89 VL and 405 non-VL patients. HIV prevalence was found to be 12.8% (47/ 367 in the VL group compared to 7.9% (200/2526 in the non-VL group. The RDT algorithm in the VL group yielded 47 positives, 4 false positives, and 38 negatives. The same algorithm for those without VL had 200 positives, 14 false positives, and 191 negatives. Specificity and positive predictive value for the group with VL was less than the non-VL group; however, the difference was not found to be significant (p = 0.52 and p = 0.76, respectively.The test algorithm yielded a high number of HIV false positive results. However, we were unable to demonstrate a significant difference between groups with and without VL disease. This suggests that the presence of endemic visceral leishmaniasis alone cannot account for the high number of false positive HIV results in our study.

  7. Contributions of international cooperation projects to the HIV/AIDS response in China.

    Science.gov (United States)

    Sun, Jiangping; Liu, Hui; Li, Hui; Wang, Liqiu; Guo, Haoyan; Shan, Duo; Bulterys, Marc; Korhonen, Christine; Hao, Yang; Ren, Minghui

    2010-12-01

    For 20 years, China has participated in 267 international cooperation projects against the HIV/AIDS epidemic and received ∼526 million USD from over 40 international organizations. These projects have played an important role by complementing national efforts in the fight against HIV/AIDS in China. The diverse characteristics of these projects followed three phases over 20 years. Initially, stand-alone projects provided technical support in surveillance, training or advocacy for public awareness. As the epidemic spread across China, projects became a part of the comprehensive and integrated national response. Currently, international best practices encourage the inclusion of civil society and non-governmental organizations in an expanded response to the epidemic. Funding from international projects has accounted for one-third of the resources provided for the HIV/AIDS response in China. Beyond this strong financial support, these programmes have introduced best practices, accelerated the introduction of AIDS policies, strengthened capacity, improved the development of grassroots social organizations and established a platform for communication and experience sharing with the international community. However, there are still challenges ahead, including integrating existing resources and exploring new programme models. The National Centre for AIDS/STD Control and Prevention (NCAIDS) in China is consolidating all international projects into national HIV prevention, treatment and care activities. International cooperation projects have been an invaluable component of China's response to HIV/AIDS, and China has now been able to take this information and share its experiences with other countries with the help of these same international programmes.

  8. Validity of impedance-based predictions of total body water as measured by 2H dilution in African HIV/AIDS outpatients

    International Nuclear Information System (INIS)

    Diouf, Adama; Idohou Dossou, Nicole; Wade, Salimata; Gartner, Agnes; Sanon, Dominique Alexis; Bluck, Les; Wright, Antony

    2009-01-01

    Measurements of body composition are crucial in identifying HIV-infected patients at risk of malnutrition. No information is available on the validity of indirect body composition methods in African HIV-infected outpatients. Our aim was to test the validity of fifteen published equations, developed in whites, African-Americans and/or Africans who were or not HIV-infected, for predicting total body water (TBW) from bioelectrical impedance analysis (BIA) in HIV-infected patients. The second aim was to develop specific predictive equations. Thirty-four HIV-infected patients without antiretroviral treatment and oedema at the beginning of the study (age 39 (SD 7) years, BMI 18.7 (SD 3.7) kg/m2, TBW 30.4 (SD 7.2 kg) were measured at inclusion then 3 and 6 months later. In the resulting eighty-eight measurements, we compared TBW values predicted from BIA to those measured by 2H dilution. Range of bias values was 0.1-4.3, and errors showed acceptable values (2.2-3.4 kg) for fourteen equations and a high value (10.4) for one equation. Two equations developed in non-HIV-infected subjects showed non-significant bias and could be used in African HIV-infected patients. In the other cases, poor agreement indicated a lack of validity. Specific equations developed from our sample showed a higher precision of TBW prediction when using resistance at 1000kHz (1.7kg) than at 50kHz (2.3kg), this latter precision being similar to that of the valid published equations (2.3 and 2.8kg). The valid published or developed predictive equations should be cross-validated in large independent samples of African HIV-infected patients. (Authors)

  9. Carnauba wax nanoparticles enhance strong systemic and mucosal cellular and humoral immune responses to HIV-gp140 antigen.

    Science.gov (United States)

    Arias, Mauricio A; Loxley, Andrew; Eatmon, Christy; Van Roey, Griet; Fairhurst, David; Mitchnick, Mark; Dash, Philip; Cole, Tom; Wegmann, Frank; Sattentau, Quentin; Shattock, Robin

    2011-02-01

    Induction of humoral responses to HIV at mucosal compartments without inflammation is important for vaccine design. We developed charged wax nanoparticles that efficiently adsorb protein antigens and are internalized by DC in the absence of inflammation. HIV-gp140-adsorbed nanoparticles induced stronger in vitro T-cell proliferation responses than antigen alone. Such responses were greatly enhanced when antigen was co-adsorbed with TLR ligands. Immunogenicity studies in mice showed that intradermal vaccination with HIV-gp140 antigen-adsorbed nanoparticles induced high levels of specific IgG. Importantly, intranasal immunization with HIV-gp140-adsorbed nanoparticles greatly enhanced serum and vaginal IgG and IgA responses. Our results show that HIV-gp140-carrying wax nanoparticles can induce strong cellular/humoral immune responses without inflammation and may be of potential use as effective mucosal adjuvants for HIV vaccine candidates. Copyright © 2010 Elsevier Ltd. All rights reserved.

  10. The effects of national and international HIV/AIDS funding and governance mechanisms on the development of civil-society responses to HIV/AIDS in East and Southern Africa.

    Science.gov (United States)

    Kelly, Kevin J; Birdsall, Karen

    2010-01-01

    The study takes stock of the exponential growth in the number of new civil-society organisations (CSOs) working in the HIV/AIDS field in East and Southern Africa during the period 1996-2004. We researched this development through a survey of 439 CSOs in six countries and case studies focused on the evolution of community responses to HIV/AIDS in specific communities in eight countries. We describe the types of CSOs that emerged, their relationships with governments and donors, and their activities, organisational characteristics and funding requirements. The data presented show that the vision of social mobilisation of HIV/AIDS responses through community-level organisations has faced strong external challenges. Evidence from survey data, national HIV/AIDS spending assessments and case studies shows that in some respects the changing international aid environment undermines the prospects for development of the civil-society sector's contributions in HIV/AIDS responses. Of particular interest is to understand how the "Three Ones" and the Paris Declaration on Aid Effectiveness have reshaped international funding for HIV/AIDS responses. There has been relatively little attention paid to the impact of the new management and funding modalities--including national performance frameworks, general budget support, joint funding arrangements and basket funds--on civil-society agencies at the forefront of community HIV/AIDS responses. Evidence is presented to show that in important respects the new modalities limit the unique contribution that CSOs can make to national HIV/AIDS responses. It is also shown that the drive to rapidly intensify the scale of HIV/AIDS responses has involved using community organisations as service providers for externally formulated programmes. We discuss this as a strong threat to the development of sustainable civil-society economies as well as to CSOs' diversity and responsiveness. The ways in which CSOs are responding to these challenges are

  11. Lipoprotein(a) and HIV: Allele-Specific Apolipoprotein(a) Levels Predict Carotid Intima-Media Thickness in HIV-Infected Young Women in the Women's Interagency HIV Study.

    Science.gov (United States)

    Enkhmaa, Byambaa; Anuurad, Erdembileg; Zhang, Wei; Li, Chin-Shang; Kaplan, Robert; Lazar, Jason; Merenstein, Dan; Karim, Roksana; Aouizerat, Brad; Cohen, Mardge; Butler, Kenneth; Pahwa, Savita; Ofotokun, Igho; Adimora, Adaora A; Golub, Elizabeth; Berglund, Lars

    2017-05-01

    In the general population, lipoprotein(a) [Lp(a)] has been established as an independent causal risk factor for cardiovascular disease. Lp(a) levels are to a major extent regulated by a size polymorphism in the apolipoprotein(a) [apo(a)] gene. The roles of Lp(a)/apo(a) in human immunodeficiency virus (HIV)-related elevated cardiovascular disease risk remain unclear. The associations between total plasma Lp(a) level, allele-specific apo(a) level, an Lp(a) level carried by individual apo(a) alleles, and common carotid artery intima-media thickness were assessed in 150 HIV-infected and 100 HIV-uninfected women in the WIHS (Women's Interagency HIV Study). Linear regression analyses with and without adjustments were used. The cohort was young (mean age, ≈31 years), with the majority being Blacks (≈70%). The prevalence of a small size apo(a) (≤22 Kringle repeats) or a high Lp(a) level (≥30 mg/dL) was similar by HIV status. Total plasma Lp(a) level ( P =0.029) and allele-specific apo(a) level carried by the smaller apo(a) sizes ( P =0.022) were significantly associated with carotid artery intima-media thickness in the HIV-infected women only. After accounting for confounders (age, race, smoking, body mass index, blood pressure, hepatitis C virus coinfection, menopause, plasma lipids, treatment status, CD4 + T cell count, and HIV/RNA viral load), the association remained significant for both Lp(a) ( P =0.035) and allele-specific apo(a) level carried by the smaller apo(a) sizes ( P =0.010) in the HIV-infected women. Notably, none of the other lipids/lipoproteins was associated with carotid artery intima-media thickness. Lp(a) and allele-specific apo(a) levels predict carotid artery intima-media thickness in HIV-infected young women. Further research is needed to identify underlying mechanisms of an increased Lp(a) atherogenicity in HIV infection. © 2017 American Heart Association, Inc.

  12. Immune activation and HIV-specific T cell responses are modulated by a cyclooxygenase-2 inhibitor in untreated HIV-infected individuals: An exploratory clinical trial.

    Directory of Open Access Journals (Sweden)

    Christian Prebensen

    Full Text Available Pathologically elevated immune activation and inflammation contribute to HIV disease progression and immunodeficiency, potentially mediated by elevated levels of prostaglandin E2, which suppress HIV-specific T cell responses. We have previously shown that a high dose of the cyclooxygenase-2 inhibitor celecoxib can reduce HIV-associated immune activation and improve IgG responses to T cell-dependent vaccines. In this follow-up study, we included 56 HIV-infected adults, 28 antiretroviral therapy (ART-naïve and 28 on ART with undetectable plasma viremia but CD4 counts below 500 cells/μL. Patients in each of the two study groups were randomized to receive 90 mg qd of the cyclooxygenase-2 inhibitor etoricoxib for six months, two weeks or to a control arm, respectively. T cell activation status, HIV Gag-specific T cell responses and plasma inflammatory markers, tryptophan metabolism and thrombin generation were analyzed at baseline and after four months. In addition, patients received tetanus toxoid, conjugated pneumococcal and seasonal influenza vaccines, to which IgG responses were determined after four weeks. In ART-naïve patients, etoricoxib reduced the density of the activation marker CD38 in multiple CD8+ T cell subsets, improved Gag-specific T cell responses, and reduced in vitro plasma thrombin generation, while no effects were seen on plasma markers of inflammation or tryptophan metabolism. No significant immunological effects of etoricoxib were observed in ART-treated patients. Patients receiving long-term etoricoxib treatment had poorer tetanus toxoid and conjugated pneumococcal vaccine responses than those receiving short-course etoricoxib. Cyclooxygenase-2 inhibitors may attenuate harmful immune activation in HIV-infected patients without access to ART.

  13. Ethnic Comparisons in HIV Testing Attitudes, HIV Testing, and Predictors of HIV Testing Among Black and White College Students.

    Science.gov (United States)

    Moore, Melanie P; Javier, Sarah J; Abrams, Jasmine A; McGann, Amanda Wattenmaker; Belgrave, Faye Z

    2017-08-01

    This study's primary aim was to examine ethnic differences in predictors of HIV testing among Black and White college students. We also examined ethnic differences in sexual risk behaviors and attitudes toward the importance of HIV testing. An analytic sample of 126 Black and 617 White undergraduatestudents aged 18-24 were analyzed for a subset of responses on the American College Health Association-National College Health Assessment II (ACHA-NCHA II) (2012) pertaining to HIV testing, attitudes about the importance of HIV testing, and sexual risk behaviors. Predictors of HIV testing behavior were analyzed using logistic regression. t tests and chi-square tests were performed to access differences in HIV test history, testing attitudes, and sexual risk behaviors. Black students had more positive attitudes toward testing and were more likely to have been tested for HIV compared to White students. A greater number of sexual partners and more positive HIV testing attitudes were significant predictors of HIV testing among White students, whereas relationship status predicted testing among Black students. Older age and history of ever having sex were significant predictors of HIV testing for both groups. There were no significant differences between groups in number of sexual partners or self-reports in history of sexual experience (oral, vaginal, or anal). Factors that influence HIV testing may differ across racial/ethnic groups. Findings support the need to consider racial/ethnic differences in predictors of HIV testing during the development and tailoring of HIV testing prevention initiatives targeting college students.

  14. IP-10 predicts the first phase decline of HCV RNA and overall viral response to therapy in patients co-infected with chronic hepatitis C virus infection and HIV

    DEFF Research Database (Denmark)

    Falconer, Karolin; Askarieh, Galia; Weis, Nina Margrethe

    2010-01-01

    The aim of this study was to investigate the utility of baseline plasma interferon-gamma inducible protein-10 (IP-10) levels in human immunodeficiency virus (HIV)-hepatitis C virus (HCV) co-infected patients. Baseline IP-10 was monitored during HCV combination therapy in 21 HIV-HCV co-infected pa......The aim of this study was to investigate the utility of baseline plasma interferon-gamma inducible protein-10 (IP-10) levels in human immunodeficiency virus (HIV)-hepatitis C virus (HCV) co-infected patients. Baseline IP-10 was monitored during HCV combination therapy in 21 HIV-HCV co......-10 viral response to HCV therapy in HIV-HCV co-infected patients, and may thus be useful in encouraging such difficult-to-treat patients to initiate therapy....

  15. Research Notes ~ Combating HIV/AIDS Epidemic in Nigeria: Responses from National Open University of Nigeria (NOUN

    Directory of Open Access Journals (Sweden)

    Terhemba Nom Ambe-Uva

    2007-11-01

    Full Text Available Universities have come under serious attack because of their lackluster response to HIV/AIDS. This article examines the response of National Open University of Nigeria (NOUN and its strategic responses in combating HIV/AIDS epidemic. This is achieved by examining NOUN’s basic structures that position the University to respond to the epidemic; and second, by assessing HIV/AIDS strategies and policy framework the University has put in place. An interpretative epistemological stance was used for this study, and a qualitative research involving focus group discussion (FGD and analysis of secondary data was carried out. Results showed that NOUN has identified the impact the epidemic has on the university, although it has yet to institutionalize an HIV/AIDS policy. NOUN’s Draft Service Charter, however, has identified the fight against HIV/AIDS as a core mandate of the University, and the introduction of HIV/AIDS certification programs can be viewed as proactive policies in response to the epidemic. Results of this study are discussed in terms of their relevance to future research and the impact such policy frameworks may have on combating the epidemic, both within the University and the wider community.

  16. Caregiver Responsiveness to the Family Bereavement Program: What predicts responsiveness? What does responsiveness predict?

    OpenAIRE

    Schoenfelder, Erin N.; Sandler, Irwin N.; Millsap, Roger E.; Wolchik, Sharlene A.; Berkel, Cady; Ayers, Timothy S.

    2013-01-01

    The study developed a multi-dimensional measure to assess participant responsiveness to a preventive intervention, and applied this measure to study how participant baseline characteristics predict responsiveness and how responsiveness predicts program outcomes. The study was conducted with caregivers who participated in the parenting-focused component of the Family Bereavement Program (FBP), a prevention program for families that have experienced parental death. The sample consisted of 89 ca...

  17. Ribavirin Concentrations Do Not Predict Sustained Virological Response in HIV/HCV-Coinfected Patients Treated with Ribavirin and Pegylated Interferon in the Swiss HIV Cohort Study.

    Directory of Open Access Journals (Sweden)

    Helen Kovari

    Full Text Available Ribavirin (RBV is an essential component of most current hepatitis C (HCV treatment regimens and still standard of care in the combination with pegylated interferon (pegIFN to treat chronic HCV in resource limited settings. Study results in HIV/HCV-coinfected patients are contradicting as to whether RBV concentration correlates with sustained virological response (SVR.We included 262 HCV treatment naïve HIV/HCV-coinfected Swiss HIV Cohort Study (SHCS participants treated with RBV and pegIFN between 01.01.2001-01.01.2010, 134 with HCV genotype (GT 1/4, and 128 with GT 2/3 infections. RBV levels were measured retrospectively in stored plasma samples obtained between HCV treatment week 4 and end of therapy. Uni- and multivariable logistic regression analyses were used to evaluate the association between RBV concentration and SVR in GT 1/4 and GT 2/3 infections. The analyses were repeated stratified by treatment phase (week 4-12, 13-24, >24 and IL28B genotype (CC versus CT/TT.SVR rates were 35.1% in GT 1/4 and 70.3% in GT 2/3 infections. Overall, median RBV concentration was 2.0 mg/L in GT 1/4, and 1.9 mg/L in GT 2/3, and did not change significantly across treatment phases. Patients with SVR had similar RBV concentrations compared to patients without SVR in both HCV genotype groups. SVR was not associated with RBV levels ≥2.0 mg/L (GT 1/4, OR 1.19 [0.5-2.86]; GT 2/3, 1.94 [0.78-4.80] and ≥2.5 mg/L (GT 1/4, 1.56 [0.64-3.84]; GT 2/3 2.72 [0.85-8.73], regardless of treatment phase, and IL28B genotype.In HIV/HCV-coinfected patients treated with pegIFN/RBV, therapeutic drug monitoring of RBV concentrations does not enhance the chance of HCV cure, regardless of HCV genotype, treatment phase and IL28B genotype.

  18. Virological and immunological response to antiretroviral regimens containing maraviroc in HIV type 1-infected patients in clinical practice: role of different tropism testing results and of concomitant treatments.

    Science.gov (United States)

    Rossetti, Barbara; Bianco, Claudia; Bellazzi, Lara Ines; Bruzzone, Bianca; Colao, Grazia; Corsi, Paola; Monno, Laura; Pagano, Gabriella; Paolucci, Stefania; Punzi, Grazia; Setti, Maurizio; Zazzi, Maurizio; De Luca, Andrea

    2014-01-01

    We assessed the immunovirological response to antiretroviral regimens containing maraviroc in HIV-infected viremic patients with viral tropism predicted by different assays. We selected antiretroviral treatment-experienced HIV-1-infected patients initiating regimens containing maraviroc after different phenotypic or genotypic viral tropism assays, with at least one HIV-1 RNA determination during follow-up. Survival analysis was employed to assess the virological response as time to HIV-1 RNA immunological response as time to a CD4 cell count increase of ≥ 100/μl from baseline. Predictors of these outcomes were analyzed by multivariate Cox regression models. In 191 treatments with maraviroc, virological response was achieved in 65.4% and the response was modestly influenced by the baseline viral load and concomitant drug activity but not influenced by the type of tropism assay employed. Immunological response was achieved in 58.1%; independent predictors were baseline HIV-1 RNA (per log10 higher: HR 1.29, 95% CI 1.05-1.60) and concomitant therapy with enfuvirtide (HR 2.05, 0.96-4.39) but not tropism assay results. Of 17 patients with baseline R5-tropic virus and available tropism results while viremic during follow-up on maraviroc, seven (41%) showed a tropism switch to non-R5 virus. A significant proportion of experienced patients treated with regimens containing maraviroc achieved virological response. The tropism test type used was not associated with immunovirological response and concomitant treatment with enfuvirtide increased the chance of immunological response. More than half of virological failures with maraviroc were not accompanied by tropism switch.

  19. Evolution of Neutralization Response in HIV-1 Subtype C-Infected Individuals Exhibiting Broad Cross-Clade Neutralization of HIV-1 Strains

    Directory of Open Access Journals (Sweden)

    Narayanaiah Cheedarla

    2018-03-01

    Full Text Available Strain-specific neutralizing antibodies develop in all human immunodeficiency virus type 1 (HIV-1-infected individuals. However, only 10–30% of infected individuals produce broadly neutralizing antibodies (bNAbs. Identification and characterization of these bNAbs and understanding their evolution dynamics are critical for obtaining useful clues for the development of an effective HIV vaccine. Very recently, we published a study in which we identified 12 HIV-1 subtype C-infected individuals from India whose plasma showed potent and broad cross-clade neutralization (BCN ability (1. In the present study, we report our findings on the evolution of host bNAb response over a period of 4 years in a subset of these individuals. Three of the five individuals (NAB033, NAB059, and NAB065 demonstrated a significant increase (p < 0.05 in potency. Interestingly, two of the three samples also showed a significant increase in CD4 binding site-specific antibody response, maintained stable CD4+ T cell counts (>350 cells/mm3 and continued to remain ART-naïve for more than 10 years after initial diagnosis, implying a strong clinical correlation with the development and evolution of broadly neutralizing antibody response against HIV-1.

  20. 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.

  1. Observed versus predicted cardiovascular events and all-cause death in HIV infection: a longitudinal cohort study.

    Science.gov (United States)

    De Socio, Giuseppe Vittorio; Pucci, Giacomo; Baldelli, Franco; Schillaci, Giuseppe

    2017-06-12

    The aim of the study was to assess the applicability of an algorithm predicting 10-year cardiovascular disease (CVD) generated in the setting of the Framingham Heart Study to a real-life, contemporary Italian cohort of HIV-positive subjects. The study was an observational longitudinal cohort study. The probability for 10-year CVD events according to the Framingham algorithm was assessed in 369 consecutive HIV-positive participants free from overt CVD enrolled in 2004, who were followed for a median of 10.0 years (interquartile range, 9.1-10.1). Cardiovascular events included myocardial infarction, hospitalized heart failure, revascularized angina, sudden cardiac death, stroke, peripheral arterial disease. Over 3097 person-years of observation, we observed a total of 34 CVD events, whereas Framingham algorithm predicted the occurrence of 34.3 CVD events. CVD event rate was 11.0/1000 person-years of follow-up. In a receiver operating characteristics curve analysis, Framingham risk equation showed an excellent predictive value for incident CVD events (c-statistics, 0.83; 95% confidence interval, 0.76-0.90). In a multivariable Cox analysis, age, smoking and diabetes were independent predictors of CVD events. All-cause death rate was 20.0/1000 person-years of follow-up (n = 62 deaths). Causes of death included liver diseases (18), malignancies (14), AIDS-related (11); cardiovascular (9) and others (10). In a Cox analysis, age, AIDS diagnosis and chronic hepatitis were independent predictors of death. Observed CVD events in HIV-infected patients were well predicted by Framingham algorithm. Established major CVD risk factors are the strongest determinants of CVD morbidity in an Italian contemporary cohort of HIV-positive subjects. Interventions to modify traditional risk factors are urgently needed in HIV people.

  2. From HIV infection to therapeutic response: a population-based longitudinal HIV cascade-of-care study in KwaZulu-Natal, South Africa.

    Science.gov (United States)

    Haber, Noah; Tanser, Frank; Bor, Jacob; Naidu, Kevindra; Mutevedzi, Tinofa; Herbst, Kobus; Porter, Kholoud; Pillay, Deenan; Bärnighausen, Till

    2017-05-01

    Standard approaches to estimation of losses in the HIV cascade of care are typically cross-sectional and do not include the population stages before linkage to clinical care. We used indiviual-level longitudinal cascade data, transition by transition, including population stages, both to identify the health-system losses in the cascade and to show the differences in inference between standard methods and the longitudinal approach. We used non-parametric survival analysis to estimate a longitudinal HIV care cascade for a large population of people with HIV residing in rural KwaZulu-Natal, South Africa. We linked data from a longitudinal population health surveillance (which is maintained by the Africa Health Research Institute) with patient records from the local public-sector HIV treatment programme (contained in an electronic clinical HIV treatment and care database, ARTemis). We followed up all people who had been newly detected as having HIV between Jan 1, 2006, and Dec 31, 2011, across six cascade stages: three population stages (first positive HIV test, HIV status knowledge, and linkage to care) and three clinical stages (eligibility for antiretroviral therapy [ART], initiation of ART, and therapeutic response). We compared our estimates to cross-sectional cascades in the same population. We estimated the cumulative incidence of reaching a particular cascade stage at a specific time with Kaplan-Meier survival analysis. Our population consisted of 5205 individuals with HIV who were followed up for 24 031 person-years. We recorded 598 deaths. 4539 individuals gained knowledge of their positive HIV status, 2818 were linked to care, 2151 became eligible for ART, 1839 began ART, and 1456 had successful responses to therapy. We used Kaplan-Meier survival analysis to adjust for censorship due to the end of data collection, and found that 8 years after testing positive in the population health surveillance, 16% had died. Among living patients, 82% knew their HIV

  3. ORIGINAL ARTICLES HIV prevention responsibilities in HIV vaccine ...

    African Journals Online (AJOL)

    HIV/AIDS Vaccines Ethics Group (HAVEG), School of Psychology, University of. KwaZulu-Natal ... receive access to risk reduction counselling on safer sex, education .... debate regarding how to proceed should acyclovir have shown to decrease HIV ... or a single pivotal trial (phase III trial) that provides as much evidence of ...

  4. HIV-1–Infected Individuals in Antiretroviral Therapy React Specifically With Polyfunctional T-Cell Responses to Gag p24

    DEFF Research Database (Denmark)

    Brandt, Lea; Benfield, Thomas; Kronborg, Gitte

    2013-01-01

    Still no effective HIV-1 prophylactic or therapeutic vaccines are available. However, as the proportion of HIV-1-infected individuals on antiretroviral treatment is increasing, knowledge about the residual immune response is important for the possible development of an HIV-1 vaccine.......Still no effective HIV-1 prophylactic or therapeutic vaccines are available. However, as the proportion of HIV-1-infected individuals on antiretroviral treatment is increasing, knowledge about the residual immune response is important for the possible development of an HIV-1 vaccine....

  5. Building political will for HIV response: an operational model and strategy options.

    Science.gov (United States)

    Brinkerhoff, Derick W

    2016-10-01

    As global programs for HIV response look to transfer responsibility and financing increasingly to country governments, the political will to take on these responsibilities becomes increasingly prominent. However, defining and assessing political will are problematic; it involves intent and motivation, and thus is inherently difficult to observe. It is intimately connected to capacity and is contextually embedded. This article describes an operational model of political will comprised of seven components that are observable and measurable. Two case studies illustrate the application of the model and shed light on the interconnections among commitment, capacity and context: South Africa and China. Strategy options to build political will for HIV response identify possible actions for both government and civil society. Political will as a concept is most usefully viewed as integrated within larger political and bureaucratic processes, as a product of the complex array of incentives and disincentives that those processes create. However, this conclusion is not a recipe for discouragement or inaction. Agent-based conceptualizations of policy change offer a solid grounding for building political will that supports HIV policy and programs. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

  6. HIV Stigma and Depressive Symptoms are Related to Adherence and Virological Response to Antiretroviral Treatment Among Immigrant and Indigenous HIV Infected Patients

    NARCIS (Netherlands)

    Sumari-de Boer, I. Marion; Sprangers, Mirjam A. G.; Prins, Jan M.; Nieuwkerk, Pythia T.

    2012-01-01

    We compared adherence to cART and viro-logical response between indigenous and immigrant HIV-infected patients in the Netherlands, and investigated if a possible difference was related to a difference in the psychosocial variables: HIV-stigma, quality-of-life, depression and beliefs about

  7. Immunological Response of Hiv-Infected Children to Highly Active Antiretoviral Therapy at Gondar University Hospital, North-Western Ethiopia.

    Science.gov (United States)

    Kokeb, Mehretie; Degu, Getu

    2016-01-01

    The effectiveness of highly active antiretroviral therapy (HAART) in children has not been well studied specially in developing countries where the burden of HIV is high. This study was aimed to assess the immunologic response of HIV-infected children to HAART at Pediatric ART Clinic Gondar University Hospital. Institution based cross-sectional study was conducted at the Pediatric ART Clinic Gondar University Hospital from March 01-April 30, 2014. The study included 283 HIV-infected children who were on HAART for 6 months and above. Medical records of HIV-infected children were reviewed using pre-tested questionnaire. CD4 count/percent was collected every 6 months retrospectively. For all statistical significance tests, the cut-off value was pimmunological response. The study revealed that there was good Immunological response to ART, and that the maximum response was in the 1(st) 6 months of ART. Low CD4 count at initiation, undisclosed HIV status and lack of good adherence were found to cause low immunological response to HAART.

  8. Response to 2009 pandemic and seasonal influenza vaccines co-administered to HIV-infected and HIV-uninfected former drug users living in a rehabilitation community in Italy.

    Science.gov (United States)

    Pariani, Elena; Boschini, Antonio; Amendola, Antonella; Poletti, Raffaella; Anselmi, Giovanni; Begnini, Marco; Ranghiero, Alberto; Cecconi, Gianluca; Zanetti, Alessandro R

    2011-11-15

    2009 A(H1N1) pandemic influenza vaccination was recommended as a priority to essential workers and high-risk individuals, including HIV-infected patients and people living in communities. HIV-infected and HIV-uninfected former drug-users (18-60 years old) living in a rehabilitation community (San Patrignano, Italy) received one dose of a MF59-adjuvanted 2009 pandemic influenza vaccine and one dose of a 2009-2010 seasonal trivalent inactivated influenza vaccine (containing A/Brisbane/59/2007(H1N1), A/Brisbane/10/2007(H3N2), B/Brisbane/60/2008) simultaneously. Antibodies against each vaccine antigen were determined at the time of vaccination and one and six months post-vaccination by hemagglutination-inhibition test. 49 HIV-infected and 60 HIV-uninfected subjects completed the study. Most (98%) HIV-infected participants were on antiretroviral treatment, the median CD4+ cell count was 350 (IQR 300)cells/μl and viremia was suppressed in 91.8% of cases. One month post-vaccination, no significant changes in immune-virological parameters were observed. One month post-vaccination, the immune responses to both pandemic and seasonal vaccine met the EMA-CPMP criteria for immunogenicity of influenza vaccines in both HIV-infected and HIV-uninfected subjects. No difference in vaccine responses was observed between the two groups. Six months after vaccination, the percentages of vaccinees with antibody titres ≥1:40 and antibody geometric mean titres significantly decreased in both groups. However, they were significantly lower in HIV-infected than in HIV-uninfected vaccinees. In subjects who had been primed to seasonal influenza the year before (through either vaccination or natural infection), levels of antibodies against 2009 A(H1N1) were higher than those measured in unprimed subjects, both one month and six months post-vaccination. The co-administration of a single dose of 2009 pandemic MF59-adjuvanted influenza vaccine with a seasonal vaccine provided a protective immune

  9. View of God as benevolent and forgiving or punishing and judgmental predicts HIV disease progression.

    Science.gov (United States)

    Ironson, Gail; Stuetzle, Rick; Ironson, Dale; Balbin, Elizabeth; Kremer, Heidemarie; George, Annie; Schneiderman, Neil; Fletcher, Mary Ann

    2011-12-01

    This study assessed the predictive relationship between View of God beliefs and change in CD4-cell and Viral Load (VL) in HIV positive people over an extended period. A diverse sample of HIVseropositive participants (N = 101) undergoing comprehensive psychological assessment and blood draws over the course of 4 years completed the View of God Inventory with subscales measuring Positive View (benevolent/forgiving) and Negative View of God (harsh/judgmental/punishing). Adjusting for initial disease status, age, gender, ethnicity, education, and antiretroviral medication (at every 6-month visit), a Positive View of God predicted significantly slower disease-progression (better preservation of CD4-cells, better control of VL), whereas a Negative View of God predicted faster disease-progression over 4 years. Effect sizes were greater than those previously demonstrated for psychosocial variables known to predict HIV-disease-progression, such as depression and coping. Results remained significant even after adjusting for church attendance and psychosocial variables (health behaviors, mood, and coping). These results provide good initial evidence that spiritual beliefs may predict health outcomes.

  10. MR brain volumetric measurements are predictive of neurobehavioral impairment in the HIV-1 transgenic rat.

    Science.gov (United States)

    Casas, Rafael; Muthusamy, Siva; Wakim, Paul G; Sinharay, Sanhita; Lentz, Margaret R; Reid, William C; Hammoud, Dima A

    2018-01-01

    HIV infection is known to be associated with brain volume loss, even in optimally treated patients. In this study, we assessed whether dynamic brain volume changes over time are predictive of neurobehavorial performance in the HIV-1 transgenic (Tg) rat, a model of treated HIV-positive patients. Cross-sectional brain MRI imaging was first performed comparing Tg and wild type (WT) rats at 3 and 19 months of age. Longitudinal MRI and neurobehavioral testing of another group of Tg and WT rats was then performed from 5 to 23 weeks of age. Whole brain and subregional image segmentation was used to assess the rate of brain growth over time. We used repeated-measures mixed models to assess differences in brain volumes and to establish how predictive the volume differences are of specific neurobehavioral deficits. Cross-sectional imaging showed smaller whole brain volumes in Tg compared to WT rats at 3 and at 19 months of age. Longitudinally, Tg brain volumes were smaller than age-matched WT rats at all time points, starting as early as 5 weeks of age. The Tg striatal growth rate delay between 5 and 9 weeks of age was greater than that of the whole brain. Striatal volume in combination with genotype was the most predictive of rota-rod scores and in combination with genotype and age was the most predictive of total exploratory activity scores in the Tg rats. The disproportionately delayed striatal growth compared to whole brain between 5 and 9 weeks of age and the role of striatal volume in predicting neurobehavioral deficits suggest an important role of the dopaminergic system in HIV associated neuropathology. This might explain problems with motor coordination and executive decisions in this animal model. Smaller brain and subregional volumes and neurobehavioral deficits were seen as early as 5 weeks of age, suggesting an early brain insult in the Tg rat. Neuroprotective therapy testing in this model should thus target this early stage of development, before brain

  11. Induction of IL21 in Peripheral T Follicular Helper Cells Is an Indicator of Influenza Vaccine Response in a Previously Vaccinated HIV-Infected Pediatric Cohort.

    Science.gov (United States)

    de Armas, Lesley R; Cotugno, Nicola; Pallikkuth, Suresh; Pan, Li; Rinaldi, Stefano; Sanchez, M Celeste; Gonzalez, Louis; Cagigi, Alberto; Rossi, Paolo; Palma, Paolo; Pahwa, Savita

    2017-03-01

    HIV-infected patients of all ages frequently underperform in response to seasonal influenza vaccination, despite virologic control of HIV. The molecular mechanisms governing this impairment, as well as predictive biomarkers for responsiveness, remain unknown. This study was performed in samples obtained prevaccination (T0) from HIV-infected children who received the 2012-2013 seasonal influenza vaccine. Response status was determined based on established criterion for hemagglutination inhibition titer; participants with a hemagglutination titer ≥1:40 plus a ≥4-fold increase over T0 at 3 wk postvaccination were designated as responders. All children had a history of prior influenza vaccinations. At T0, the frequencies of CD4 T cell subsets, including peripheral T follicular helper (pTfh) cells, which provide help to B cells for developing into Ab-secreting cells, were similar between responders and nonresponders. However, in response to in vitro stimulation with influenza A/California/7/2009 (H1N1) Ag, differential gene expression related to pTfh cell function was observed by Fluidigm high-density RT-PCR between responders and nonresponders. In responders, H1N1 stimulation at T0 also resulted in CXCR5 induction (mRNA and protein) in CD4 T cells and IL21 gene induction in pTfh cells that were strongly associated with H1N1-specific B cell responses postvaccination. In contrast, CD4 T cells of nonresponders exhibited increased expression of IL2 and STAT5 genes, which are known to antagonize peripheral Tfh cell function. These results suggest that the quality of pTfh cells at the time of immunization is important for influenza vaccine responses and provide a rationale for targeted, ex vivo Ag-driven molecular profiling of purified immune cells to detect predictive biomarkers of the vaccine response. Copyright © 2017 by The American Association of Immunologists, Inc.

  12. Oropharyngeal Candidiasis in HIV Infection: Analysis of Impaired Mucosal Immune Response to Candida albicans in Mice Expressing the HIV-1 Transgene

    Directory of Open Access Journals (Sweden)

    Louis de Repentigny

    2015-06-01

    Full Text Available IL-17-producing Th17 cells are of critical importance in host defense against oropharyngeal candidiasis (OPC. Speculation about defective Th17 responses to oral C. albicans infection in the context of HIV infection prompted an investigation of innate and adaptive immune responses to Candida albicans in transgenic mice expressing the genome of HIV-1 in immune cells and displaying an AIDS-like disease. Defective IL-17 and IL-22-dependent mucosal responses to C. albicans were found to determine susceptibility to OPC in these transgenic mice. Innate phagocytes were quantitatively and functionally intact, and individually dispensable for control of OPC and to prevent systemic dissemination of Candida to deep organs. CD8+ T-cells recruited to the oral mucosa of the transgenic mice limited the proliferation of C. albicans in these conditions of CD4+ T-cell deficiency. Therefore, the immunopathogenesis of OPC in the context of HIV infection involves defective T-cell-mediated immunity, failure of crosstalk with innate mucosal immune effector mechanisms, and compensatory cell responses, which limit Candida infection to the oral mucosa and prevent systemic dissemination.

  13. The initial antibody response to HIV-1: induction of ineffective early B cell responses against GP41 by the transmitted/founder virus

    Energy Technology Data Exchange (ETDEWEB)

    Chavez, Leslie L [Los Alamos National Laboratory; Perelson, Alan [Los Alamos National Laboratory

    2008-01-01

    A window of opportunity for immune responses to extinguish HIV -1 exists from the moment of transmission through establishment of the latent pool of HIV -I-infected cells. A critical time to study the initial immune responses to the transmitted/founder virus is the eclipse phase of HIV-1 infection (time from transmission to the first appearance of plasma virus) but, to date, this period has been logistically difficult to analyze. Studies in non-human primates challenged with chimeric simianhuman immunodeficiency virus have shown that neutralizing antibodies, when present at the time of infection, can prevent virus infection.

  14. Modeling the Mechanisms by Which HIV-Associated Immunosuppression Influences HPV Persistence at the Oral Mucosa.

    Science.gov (United States)

    Verma, Meghna; Erwin, Samantha; Abedi, Vida; Hontecillas, Raquel; Hoops, Stefan; Leber, Andrew; Bassaganya-Riera, Josep; Ciupe, Stanca M

    2017-01-01

    Human immunodeficiency virus (HIV)-infected patients are at an increased risk of co-infection with human papilloma virus (HPV), and subsequent malignancies such as oral cancer. To determine the role of HIV-associated immune suppression on HPV persistence and pathogenesis, and to investigate the mechanisms underlying the modulation of HPV infection and oral cancer by HIV, we developed a mathematical model of HIV/HPV co-infection. Our model captures known immunological and molecular features such as impaired HPV-specific effector T helper 1 (Th1) cell responses, and enhanced HPV infection due to HIV. We used the model to determine HPV prognosis in the presence of HIV infection, and identified conditions under which HIV infection alters HPV persistence in the oral mucosa system. The model predicts that conditions leading to HPV persistence during HIV/HPV co-infection are the permissive immune environment created by HIV and molecular interactions between the two viruses. The model also determines when HPV infection continues to persist in the short run in a co-infected patient undergoing antiretroviral therapy. Lastly, the model predicts that, under efficacious antiretroviral treatment, HPV infections will decrease in the long run due to the restoration of CD4+ T cell numbers and protective immune responses.

  15. Modeling the Mechanisms by Which HIV-Associated Immunosuppression Influences HPV Persistence at the Oral Mucosa.

    Directory of Open Access Journals (Sweden)

    Meghna Verma

    Full Text Available Human immunodeficiency virus (HIV-infected patients are at an increased risk of co-infection with human papilloma virus (HPV, and subsequent malignancies such as oral cancer. To determine the role of HIV-associated immune suppression on HPV persistence and pathogenesis, and to investigate the mechanisms underlying the modulation of HPV infection and oral cancer by HIV, we developed a mathematical model of HIV/HPV co-infection. Our model captures known immunological and molecular features such as impaired HPV-specific effector T helper 1 (Th1 cell responses, and enhanced HPV infection due to HIV. We used the model to determine HPV prognosis in the presence of HIV infection, and identified conditions under which HIV infection alters HPV persistence in the oral mucosa system. The model predicts that conditions leading to HPV persistence during HIV/HPV co-infection are the permissive immune environment created by HIV and molecular interactions between the two viruses. The model also determines when HPV infection continues to persist in the short run in a co-infected patient undergoing antiretroviral therapy. Lastly, the model predicts that, under efficacious antiretroviral treatment, HPV infections will decrease in the long run due to the restoration of CD4+ T cell numbers and protective immune responses.

  16. Cerebrospinal fluid cytokine profiles predict risk of early mortality and immune reconstitution inflammatory syndrome in HIV-associated cryptococcal meningitis.

    Directory of Open Access Journals (Sweden)

    Joseph N Jarvis

    2015-04-01

    Full Text Available Understanding the host immune response during cryptococcal meningitis (CM is of critical importance for the development of immunomodulatory therapies. We profiled the cerebrospinal fluid (CSF immune-response in ninety patients with HIV-associated CM, and examined associations between immune phenotype and clinical outcome. CSF cytokine, chemokine, and macrophage activation marker concentrations were assayed at disease presentation, and associations between these parameters and microbiological and clinical outcomes were examined using principal component analysis (PCA. PCA demonstrated a co-correlated CSF cytokine and chemokine response consisting primarily of Th1, Th2, and Th17-type cytokines. The presence of this CSF cytokine response was associated with evidence of increased macrophage activation, more rapid clearance of Cryptococci from CSF, and survival at 2 weeks. The key components of this protective immune-response were interleukin (IL-6 and interferon-γ, IL-4, IL-10 and IL-17 levels also made a modest positive contribution to the PC1 score. A second component of co-correlated chemokines was identified by PCA, consisting primarily of monocyte chemotactic protein-1 (MCP-1 and macrophage inflammatory protein-1α (MIP-1α. High CSF chemokine concentrations were associated with low peripheral CD4 cell counts and CSF lymphocyte counts and were predictive of immune reconstitution inflammatory syndrome (IRIS. In conclusion CSF cytokine and chemokine profiles predict risk of early mortality and IRIS in HIV-associated CM. We speculate that the presence of even minimal Cryptococcus-specific Th1-type CD4+ T-cell responses lead to increased recruitment of circulating lymphocytes and monocytes into the central nervous system (CNS, more effective activation of CNS macrophages and microglial cells, and faster organism clearance; while high CNS chemokine levels may predispose to over recruitment or inappropriate recruitment of immune cells to the CNS and

  17. Improved darunavir genotypic mutation score predicting treatment response for patients infected with HIRaben-1 subtype B and non-subtype B receiving a salvage regimen

    NARCIS (Netherlands)

    De Luca, Andrea; Flandre, Philippe; Dunn, David; Zazzi, Maurizio; Wensing, Annemarie; Santoro, Maria Mercedes; Günthard, Huldrych F.; Wittkop, Linda; Kordossis, Theodoros; Garcia, Federico; Castagna, Antonella; Cozzi-Lepri, Alessandro; Churchill, Duncan; De Wit, Stéphane; Brockmeyer, Norbert H.; Imaz, Arkaitz; Mussini, Cristina; Obel, Niels; Perno, Carlo Federico; Roca, Bernardino; Reiss, Peter; Schülter, Eugen; Torti, Carlo; van Sighem, Ard; Zangerle, Robert; Descamps, Diane; Mocroft, Amanda; Kirk, Ole; Sabin, Caroline; De Wit, Stéphane; Casabona, Jordi; Miró, Jose M.; Touloumi, Giota; Garrido, Myriam; Teira, Ramon; Wit, Ferdinand; Warszawski, Josiane; Meyer, Laurence; Dabis, François; Krause, Murielle Mary; Ghosn, Jade; Leport, Catherine; Prins, Maria; Bucher, Heiner; Gibb, Diana; Fätkenheuer, Gerd; del Amo, Julia; Thorne, Claire; Stephan, Christoph; Pérez-Hoyos, Santiago; Hamouda, Osamah; Bartmeyer, Barbara; Chkhartishvili, Nikoloz; Noguera-Julian, Antoni; Antinori, Andrea; d'Arminio Monforte, Antonella; Prieto, Luis; Conejo, Pablo Rojo; Soriano-Arandes, Antoni; Battegay, Manuel; Kouyos, Roger; Tookey, Pat; Konopnick, Deborah; Goetghebuer, Tessa; Sönnerborg, Anders; Haerry, David; de Wit, Stéphane; Costagliola, Dominique; Raben, Dorthe; Chêne, Geneviève; Ceccherini-Silberstein, Francesca; Günthard, Huldrych; Judd, Ali; Barger, Diana; Schwimmer, Christine; Termote, Monique; Campbell, Maria; Frederiksen, Casper M.; Friis-Møller, Nina; Kjaer, Jesper; Brandt, Rikke Salbøl; Berenguer, Juan; Bohlius, Julia; Bouteloup, Vincent; Davies, Mary Anne; Dorrucci, Maria; Egger, Matthias; Furrer, Hansjakob; Guiguet, Marguerite; Grabar, Sophie; Lambotte, Olivier; Leroy, Valériane; Lodi, Sara; Matheron, Sophie; Monge, Susana; Nakagawa, Fumiyo; Paredes, Roger; Phillips, Andrew; Puoti, Massimo; Schomaker, Michael; Smit, Colette; Sterne, Jonathan; Thiebaut, Rodolphe; van der Valk, Marc; Wyss, Natasha; Aubert, V.; Battegay, M.; Bernasconi, E.; Böni, J.; Burton-Jeangros, C.; Calmy, A.; Cavassini, M.; Dollenmaier, G.; Egger, M.; Elzi, L.; Fehr, J.; Fellay, J.; Furrer, H.; Fux, C. A.; Gorgievski, M.; Günthard, H.; Haerry, D.; Hasse, B.; Hirsch, H. H.; Hoffmann, M.; Hösli, I.; Kahlert, C.; Kaiser, L.; Keiser, O.; Klimkait, T.; Kouyos, R.; Kovari, H.; Ledergerber, B.; Martinetti, G.; Martinez de Tejada, B.; Metzner, K.; Müller, N.; Nadal, D.; Nicca, D.; Pantaleo, G.; Rauch, A.; Regenass, S.; Rickenbach, M.; Rudin, C.; Schöni-Affolter, F.; Schmid, P.; Schüpbach, J.; Speck, R.; Tarr, P.; Telenti, A.; Trkola, A.; Vernazza, P.; Weber, R.; Yerly, S.

    2016-01-01

    Objectives: The objective of this studywas to improve the prediction of the impact of HIV-1 protease mutations in different viral subtypes on virological response to darunavir. Methods: Darunavir-containing treatment change episodes (TCEs) in patients previously failing PIs were selected from large

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

    Directory of Open Access Journals (Sweden)

    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.

  19. Characterization of Gag and Nef-specific ELISpot-based CTL responses in HIV-1 infected Indian individuals.

    Science.gov (United States)

    Mendiratta, Sanjay; Vajpayee, Madhu; Malhotra, Uma; Kaushik, Shweta; Dar, Lalit; Mojumdar, Kamalika; Chauhan, Neeraj Kumar; Sreenivas, Vishnubhatla

    2009-02-01

    Cytotoxic T lymphocyte (CTL) responses to Gag have been most frequently linked to control of viremia whereas CTL responses to Nef have direct relationship with viral load. IFN-gamma ELISpot assay was used to screen CTL responses at single peptide level directed at HIV-1 subtype C Gag and Nef proteins in 30 antiretroviral therapy naive HIV-1 infected Indian individuals. PBMCs from 73.3% and 90% of the study population showed response to Gag and Nef antigens, respectively. The magnitude of Gag-specific CTL responses was inversely correlated with plasma viral load (r = -0.45, P = 0.001), whereas magnitude of Nef-specific responses was directly correlated (r = 0.115). Thirteen immunodominant regions (6 in Gag, 7 in Nef) were identified in the current study. The identification of Gag and Nef-specific responses across HIV-1 infected Indian population and targeting epitopes from multiple immunodominant regions may provide useful insight into the designing of new immunotherapy and vaccines.

  20. Determining a cost effective intervention response to HIV/AIDS in Peru

    Science.gov (United States)

    Aldridge, Robert W; Iglesias, David; Cáceres, Carlos F; Miranda, J Jaime

    2009-01-01

    Background The HIV epidemic in Peru is still regarded as concentrated - sentinel surveillance data shows greatest rates of infection in men who have sex with men, while much lower rates are found in female sex workers and still lower in the general population. Without an appropriate set of preventive interventions, continuing infections could present a challenge to the sustainability of the present programme of universal access to treatment. Determining how specific prevention and care strategies would impact on the health of Peruvians should be key in reshaping the national response. Methods HIV/AIDS prevalence levels for risk groups with sufficient sentinel survey data were estimated. Unit costs were calculated for a series of interventions against HIV/AIDS which were subsequently inputted into a model to assess their ability to reduce infection transmission rates. Interventions included: mass media, voluntary counselling and testing; peer counselling for female sex workers; peer counselling for men who have sex with men; peer education of youth in-school; condom provision; STI treatment; prevention of mother to child transmission; and highly active antiretroviral therapy. Impact was assessed by the ability to reduce rates of transmission and quantified in terms of cost per DALY averted. Results Results of the analysis show that in Peru, the highest levels of HIV prevalence are found in men who have sex with men. Cost effectiveness varied greatly between interventions ranging from peer education of female commercial sex workers at $US 55 up to $US 5,928 (per DALY averted) for prevention of mother to child transmission. Conclusion The results of this work add evidence-based clarity as to which interventions warrant greatest consideration when planning an intervention response to HIV in Peru. Cost effectiveness analysis provides a necessary element of transparency when facing choices about priority setting, particularly when the country plans to amplify its

  1. Determining a cost effective intervention response to HIV/AIDS in Peru

    Directory of Open Access Journals (Sweden)

    Cáceres Carlos F

    2009-09-01

    Full Text Available Abstract Background The HIV epidemic in Peru is still regarded as concentrated - sentinel surveillance data shows greatest rates of infection in men who have sex with men, while much lower rates are found in female sex workers and still lower in the general population. Without an appropriate set of preventive interventions, continuing infections could present a challenge to the sustainability of the present programme of universal access to treatment. Determining how specific prevention and care strategies would impact on the health of Peruvians should be key in reshaping the national response. Methods HIV/AIDS prevalence levels for risk groups with sufficient sentinel survey data were estimated. Unit costs were calculated for a series of interventions against HIV/AIDS which were subsequently inputted into a model to assess their ability to reduce infection transmission rates. Interventions included: mass media, voluntary counselling and testing; peer counselling for female sex workers; peer counselling for men who have sex with men; peer education of youth in-school; condom provision; STI treatment; prevention of mother to child transmission; and highly active antiretroviral therapy. Impact was assessed by the ability to reduce rates of transmission and quantified in terms of cost per DALY averted. Results Results of the analysis show that in Peru, the highest levels of HIV prevalence are found in men who have sex with men. Cost effectiveness varied greatly between interventions ranging from peer education of female commercial sex workers at $US 55 up to $US 5,928 (per DALY averted for prevention of mother to child transmission. Conclusion The results of this work add evidence-based clarity as to which interventions warrant greatest consideration when planning an intervention response to HIV in Peru. Cost effectiveness analysis provides a necessary element of transparency when facing choices about priority setting, particularly when the country

  2. Transient nature of long-term nonprogression and broad virus-specific proliferative T-cell responses with sustained thymic output in HIV-1 controllers.

    Directory of Open Access Journals (Sweden)

    Samantha J Westrop

    Full Text Available HIV-1(+ individuals who, without therapy, conserve cellular anti-HIV-1 responses, present with high, stable CD4(+ T-cell numbers, and control viral replication, facilitate analysis of atypical viro-immunopathology. In the absence of universal definition, immune function in such HIV controllers remains an indication of non-progression.CD4 T-cell responses to a number of HIV-1 proteins and peptide pools were assessed by IFN-gamma ELISpot and lymphoproliferative assays in HIV controllers and chronic progressors. Thymic output was assessed by sjTRECs levels. Follow-up of 41 HIV-1(+ individuals originally identified as "Long-term non-progressors" in 1996 according to clinical criteria, and longitudinal analysis of two HIV controllers over 22 years, was also performed. HIV controllers exhibited substantial IFN-gamma producing and proliferative HIV-1-specific CD4 T-cell responses to both recombinant proteins and peptide pools of Tat, Rev, Nef, Gag and Env, demonstrating functional processing and presentation. Conversely, HIV-specific T-cell responses were limited to IFN-gamma production in chronic progressors. Additionally, thymic output was approximately 19 fold higher in HIV controllers than in age-matched chronic progressors. Follow-up of 41 HIV-1(+ patients identified as LTNP in 1996 revealed the transitory characteristics of this status. IFN-gamma production and proliferative T-cell function also declines in 2 HIV controllers over 22 years.Although increased thymic output and anti-HIV-1 T-cell responses are observed in HIV controllers compared to chronic progressors, the nature of nonprogressor/controller status appears to be transitory.

  3. T-cell responses targeting HIV Nef uniquely correlate with infected cell frequencies after long-term antiretroviral therapy.

    Directory of Open Access Journals (Sweden)

    Allison S Thomas

    2017-09-01

    Full Text Available HIV-specific CD8+ T-cell responses limit viral replication in untreated infection. After the initiation of antiretroviral therapy (ART, these responses decay and the infected cell population that remains is commonly considered to be invisible to T-cells. We hypothesized that HIV antigen recognition may persist in ART-treated individuals due to low-level or episodic protein expression. We posited that if persistent recognition were occurring it would be preferentially directed against the early HIV gene products Nef, Tat, and Rev as compared to late gene products, such as Gag, Pol, and Env, which have higher barriers to expression. Using a primary cell model of latency, we observed that a Nef-specific CD8+ T-cell clone exhibited low-level recognition of infected cells prior to reactivation and robust recognition shortly thereafter. A Gag-specific CD8+ T-cell clone failed to recognized infected cells under these conditions, corresponding with a lack of detectable Gag expression. We measured HIV-specific T-cell responses in 96 individuals who had been suppressed on ART for a median of 7 years, and observed a significant, direct correlation between cell-associated HIV DNA levels and magnitudes of IFN-γ-producing Nef/Tat/Rev-specific T-cell responses. This correlation was confirmed in an independent cohort (n = 18. Correlations were not detected between measures of HIV persistence and T-cell responses to other HIV antigens. The correlation with Nef/Tat/Rev-specific T-cells was attributable to Nef-specific responses, the breadth of which also correlated with HIV DNA levels. These results suggest that ongoing Nef expression in ART-treated individuals drives preferential maintenance and/or expansion of T-cells reactive to this protein, implying sensing of infected cells by the immune system. The direct correlation, however, suggests that recognition does not result in efficient elimination of infected cells. These results raise the possibility that

  4. Reference curves for CD4 T-cell count response to combination antiretroviral therapy in HIV-1-infected treatment-naïve patients.

    Science.gov (United States)

    Bouteloup, V; Sabin, C; Mocroft, A; Gras, L; Pantazis, N; Le Moing, V; d'Arminio Monforte, A; Mary-Krause, M; Roca, B; Miro, J M; Battegay, M; Brockmeyer, N; Berenguer, J; Morlat, P; Obel, N; De Wit, S; Fätkenheuer, G; Zangerle, R; Ghosn, J; Pérez-Hoyos, S; Campbell, M; Prins, M; Chêne, G; Meyer, L; Dorrucci, M; Torti, C; Thiébaut, R

    2017-01-01

    The aim of this work was to provide a reference for the CD4 T-cell count response in the early months after the initiation of combination antiretroviral therapy (cART) in HIV-1-infected patients. All patients in the Collaboration of Observational HIV Epidemiological Research Europe (COHERE) cohort who were aged ≥ 18 years and started cART for the first time between 1 January 2005 and 1 January 2010 and who had at least one available measurement of CD4 count and a viral load ≤ 50 HIV-1 RNA copies/mL at 6 months (± 3 months) after cART initiation were included in the study. Unadjusted and adjusted references curves and predictions were obtained using quantile regressions. A total of 28 992 patients were included in the study. The median CD4 T-cell count at treatment initiation was 249 [interquartile range (IQR) 150, 336] cells/μL. The median observed CD4 counts at 6, 9 and 12 months were 382 (IQR 256, 515), 402 (IQR 274, 543) and 420 (IQR 293, 565) cells/μL. The two main factors explaining the variation of CD4 count at 6 months were AIDS stage and CD4 count at cART initiation. A CD4 count increase of ≥ 100 cells/mL is generally required in order that patients stay 'on track' (i.e. with a CD4 count at the same percentile as when they started), with slightly higher gains required for those starting with CD4 counts in the higher percentiles. Individual predictions adjusted for factors influencing CD4 count were more precise. Reference curves aid the evaluation of the immune response early after antiretroviral therapy initiation that leads to viral control. © 2016 British HIV Association.

  5. Decreased HIV-specific T-regulatory responses are associated with effective DC-vaccine induced immunity.

    Directory of Open Access Journals (Sweden)

    Vedran Brezar

    2015-03-01

    Full Text Available The role of regulatory T cells (Tregs in vaccination has been poorly investigated. We have reported that vaccination with ex vivo-generated dendritic-cells (DC loaded with HIV-lipopeptides (LIPO-5-DC vaccine in HIV-infected patients was well tolerated and highly immunogenic. These responses and their relation to viral replication following analytical treatment interruption (ATI were variable. Here, we investigated whether the presence of HIV-specific Tregs might explain these differences. Co-expression of CD25, CD134, CD39 and FoxP3 was used to delineate both antigen-specific Tregs and effectors T cells (Teffs. Median LIPO-5 specific-CD25+CD134+ polyfunctional T cells increased from 0.1% (IQR 0-0.3 before vaccination (week -4 to 2.1% (IQR 1.1-3.9 at week 16 following 4 immunizations (p=0.001 and were inversely correlated with maximum viral load following ATI (r=-0.77, p=0.001. Vaccinees who displayed lower levels of HIV-specific CD4+CD134+CD25+CD39+FoxP3+ Tregs responded better to the LIPO-5-DC vaccine. After vaccination, the frequency of HIV-specific Tregs decreased (from 69.3 at week -4 to 31.7% at week 16 and inversely correlated with HIV-specific IFN-γ-producing cells (r=-0.64, p=0.002. We show that therapeutic immunization skewed the HIV-specific response from regulatory to effector phenotype which impacts on the magnitude of viral replication following ATI.

  6. The development of artificial neural networks to predict virological response to combination HIV therapy

    NARCIS (Netherlands)

    Larder, Brendan; Wang, Dechao; Revell, Andrew; Montaner, Julio; Harrigan, Richard; de Wolf, Frank; Lange, Joep; Wegner, Scott; Ruiz, Lidia; Pérez-Elías, Maria Jésus; Emery, Sean; Gatell, Jose; D'Arminio Monforte, Antonella; Torti, Carlo; Zazzi, Maurizio; Lane, Clifford

    2007-01-01

    When used in combination, antiretroviral drugs are highly effective for suppressing HIV replication. Nevertheless, treatment failure commonly occurs and is generally associated with viral drug resistance. The choice of an alternative regimen may be guided by a drug-resistance test. However,

  7. Increased brain-predicted aging in treated HIV disease

    NARCIS (Netherlands)

    Cole, James H; Underwood, Jonathan; Caan, Matthan W A; De Francesco, Davide; van Zoest, Rosan A; Leech, Robert; Wit, Ferdinand W N M; Portegies, Peter; Geurtsen, Gert J; Schmand, Ben A; Schim van der Loeff, Maarten F; Franceschi, Claudio; Sabin, Caroline A; Majoie, Charles B L M; Winston, Alan; Reiss, Peter; Sharp, David J; Kalsbeek, A.

    OBJECTIVE: To establish whether HIV disease is associated with abnormal levels of age-related brain atrophy, by estimating apparent brain age using neuroimaging and exploring whether these estimates related to HIV status, age, cognitive performance, and HIV-related clinical parameters. METHODS: A

  8. Increased brain-predicted aging in treated HIV disease

    NARCIS (Netherlands)

    Cole, James H.; Underwood, Jonathan; Caan, Matthan W. A.; de Francesco, Davide; van Zoest, Rosan A.; Leech, Robert; Wit, Ferdinand W. N. M.; Portegies, Peter; Geurtsen, Gert J.; Schmand, Ben A.; Schim van der Loeff, Maarten F.; Franceschi, Claudio; Sabin, Caroline A.; Majoie, Charles B. L. M.; Winston, Alan; Reiss, Peter; Sharp, David J.; Schouten, J.; Kooij, K. W.; Elsenga, B. C.; Janssen, F. R.; Heidenrijk, M.; Schrijver, J. H. N.; Zikkenheiner, W.; van der Valk, M.; Henderiks, A.; Kootstra, N. A.; Harskamp-Holwerda, A. M.; Maurer, I.; Ruiz, M. M. Mangas; Booiman, T.; Girigorie, A. F.; Villaudy, J.; Frankin, E.; Pasternak, A.; Berkhout, B.; van der Kuyl, T.; Stege, J. A. ter; Twennaar, M. Klein; Su, T.; Siteur-van Rijnstra, E.; Weijer, K.; Bisschop, P. H. L. T.; Kalsbeek, A.; Wezel, M.; Visser, I.; Ruhé , H. G.; Tembo, L.; Stott, M.; Prins, M. [= Maria

    2017-01-01

    To establish whether HIV disease is associated with abnormal levels of age-related brain atrophy, by estimating apparent brain age using neuroimaging and exploring whether these estimates related to HIV status, age, cognitive performance, and HIV-related clinical parameters. A large sample of

  9. The fitness landscape of HIV-1 gag: advanced modeling approaches and validation of model predictions by in vitro testing.

    Directory of Open Access Journals (Sweden)

    Jaclyn K Mann

    2014-08-01

    Full Text Available Viral immune evasion by sequence variation is a major hindrance to HIV-1 vaccine design. To address this challenge, our group has developed a computational model, rooted in physics, that aims to predict the fitness landscape of HIV-1 proteins in order to design vaccine immunogens that lead to impaired viral fitness, thus blocking viable escape routes. Here, we advance the computational models to address previous limitations, and directly test model predictions against in vitro fitness measurements of HIV-1 strains containing multiple Gag mutations. We incorporated regularization into the model fitting procedure to address finite sampling. Further, we developed a model that accounts for the specific identity of mutant amino acids (Potts model, generalizing our previous approach (Ising model that is unable to distinguish between different mutant amino acids. Gag mutation combinations (17 pairs, 1 triple and 25 single mutations within these predicted to be either harmful to HIV-1 viability or fitness-neutral were introduced into HIV-1 NL4-3 by site-directed mutagenesis and replication capacities of these mutants were assayed in vitro. The predicted and measured fitness of the corresponding mutants for the original Ising model (r = -0.74, p = 3.6×10-6 are strongly correlated, and this was further strengthened in the regularized Ising model (r = -0.83, p = 3.7×10-12. Performance of the Potts model (r = -0.73, p = 9.7×10-9 was similar to that of the Ising model, indicating that the binary approximation is sufficient for capturing fitness effects of common mutants at sites of low amino acid diversity. However, we show that the Potts model is expected to improve predictive power for more variable proteins. Overall, our results support the ability of the computational models to robustly predict the relative fitness of mutant viral strains, and indicate the potential value of this approach for understanding viral immune evasion

  10. Boosting of HIV-1 neutralizing antibody responses by a distally related retroviral envelope protein

    DEFF Research Database (Denmark)

    Uchtenhagen, Hannes; Schiffner, Torben; Bowles, Emma

    2014-01-01

    Our knowledge of the binding sites for neutralizing Abs (NAb) that recognize a broad range of HIV-1 strains (bNAb) has substantially increased in recent years. However, gaps remain in our understanding of how to focus B cell responses to vulnerable conserved sites within the HIV-1 envelope glycop...

  11. Responsibility attribution of HIV infection and coping among injection drug users in Malaysia.

    Science.gov (United States)

    Chou, Chih-Chin; Chronister, Julie; Chou, Chih-Hung; Tan, Sooyin; Macewicz, Thomas

    2013-01-01

    This study explored responsibility attribution (RA) of HIV/AIDS infection (i.e., how an individual perceives the cause of their HIV/AIDS infection) and its relationship to coping styles among injection drug users (IDUs) with HIV/AIDS. In addition, this study investigated whether self-esteem, social support, and religiosity mediate the relationship between RA and coping styles of IDUs with HIV/AIDS. Participants were 201 adult IDUs with HIV/AIDS participating in the National Drug Rehabilitation Center in Malaysia. Five measures were used to assess the above constructs. Cluster analysis, analysis of variance, and mediation analyses were conducted. Results of this study indicated that IDUs with HIV/AIDS in Malaysia can be classified into four homogenous attribution groups: external, fatalistic, internal, and indeterminate. Mediator analyses revealed that combination of self-esteem, social support, and religiosity mediate the relationship between RA and coping behaviors. Clinicians working with IDUs with HIV/AIDS need to address the role of RA, self-esteem, religiosity, and social support as these psychosocial constructs are linked to coping with HIV/AIDS. Future researchers should investigate whether enhancing self-esteem, social support, and religiosity can promote active problem-solving coping and reduce the use of avoidance coping behaviors.

  12. Usefulness of the HIV dementia scale in nigerian patients with HIV ...

    African Journals Online (AJOL)

    Saharan Africa, where statistics on HIV are alarming, is sparse because of lack of validated cognitive tools. This study assessed the usefulness and predictive validity of the HIV Dementia Scale (HDS) as a screening tool in HIV-positive Nigerians.

  13. Ex vivo response to histone deacetylase (HDAC inhibitors of the HIV long terminal repeat (LTR derived from HIV-infected patients on antiretroviral therapy.

    Directory of Open Access Journals (Sweden)

    Hao K Lu

    Full Text Available Histone deacetylase inhibitors (HDACi can induce human immunodeficiency virus (HIV transcription from the HIV long terminal repeat (LTR. However, ex vivo and in vivo responses to HDACi are variable and the activity of HDACi in cells other than T-cells have not been well characterised. Here, we developed a novel assay to determine the activity of HDACi on patient-derived HIV LTRs in different cell types. HIV LTRs from integrated virus were amplified using triple-nested Alu-PCR from total memory CD4+ T-cells (CD45RO+ isolated from HIV-infected patients prior to and following suppressive antiretroviral therapy. NL4-3 or patient-derived HIV LTRs were cloned into the chromatin forming episomal vector pCEP4, and the effect of HDACi investigated in the astrocyte and epithelial cell lines SVG and HeLa, respectively. There were no significant differences in the sequence of the HIV LTRs isolated from CD4+ T-cells prior to and after 18 months of combination antiretroviral therapy (cART. We found that in both cell lines, the HDACi panobinostat, trichostatin A, vorinostat and entinostat activated patient-derived HIV LTRs to similar levels seen with NL4-3 and all patient derived isolates had similar sensitivity to maximum HDACi stimulation. We observed a marked difference in the maximum fold induction of luciferase by HDACi in HeLa and SVG, suggesting that the effect of HDACi may be influenced by the cellular environment. Finally, we observed significant synergy in activation of the LTR with vorinostat and the viral protein Tat. Together, our results suggest that the LTR sequence of integrated virus is not a major determinant of a functional response to an HDACi.

  14. Correlating HIV tropism with immunological response under combination antiretroviral therapy.

    Science.gov (United States)

    Bader, J; Schöni-Affolter, F; Böni, J; Gorgievski-Hrisoho, M; Martinetti, G; Battegay, M; Klimkait, T

    2016-09-01

    A significant percentage of patients infected with HIV-1 experience only suboptimal CD4 cell recovery while treated with combination therapy (cART). It is still unclear whether viral properties such as cell tropism play a major role in this incomplete immune response. This study therefore intended to follow the tropism evolution of the HIV-1 envelope during periods of suppressive cART. Viruses from two distinct patient groups, one with good and another one with poor CD4 recovery after 5 years of suppressive cART, were genotypically analysed for viral tropism at baseline and at the end of the study period. Patients with CCR5-tropic CC-motif chemokine receptor 5 viruses at baseline tended to maintain this tropism to the study end. Patients who had a CXCR4-tropic CXC-motif chemokine receptor 4 virus at baseline were overrepresented in the poor CD4 recovery group. Overall, however, the majority of patients presented with CCR5-tropic viruses at follow-up. Our data lend support to the hypothesis that tropism determination can be used as a parameter for disease progression even if analysed long before the establishment of a poorer immune response. Moreover, the lasting predominating CCR5-tropism during periods of full viral control suggests the involvement of cellular mechanisms that preferentially reduce CXCR4-tropic viruses during cART. © 2016 British HIV Association.

  15. Screening Yield of HIV Antigen/Antibody Combination and Pooled HIV RNA Testing for Acute HIV Infection in a High-Prevalence Population.

    Science.gov (United States)

    Peters, Philip J; Westheimer, Emily; Cohen, Stephanie; Hightow-Weidman, Lisa B; Moss, Nicholas; Tsoi, Benjamin; Hall, Laura; Fann, Charles; Daskalakis, Demetre C; Beagle, Steve; Patel, Pragna; Radix, Asa; Foust, Evelyn; Kohn, Robert P; Marmorino, Jenni; Pandori, Mark; Fu, Jie; Samandari, Taraz; Gay, Cynthia L

    2016-02-16

    Although acute HIV infection contributes disproportionately to onward HIV transmission, HIV testing has not routinely included screening for acute HIV infection. To evaluate the performance of an HIV antigen/antibody (Ag/Ab) combination assay to detect acute HIV infection compared with pooled HIV RNA testing. Multisite, prospective, within-individual comparison study conducted between September 2011 and October 2013 in 7 sexually transmitted infection clinics and 5 community-based programs in New York, California, and North Carolina. Participants were 12 years or older and seeking HIV testing, without known HIV infection. All participants with a negative rapid HIV test result were screened for acute HIV infection with an HIV Ag/Ab combination assay (index test) and pooled human immunodeficiency virus 1 (HIV-1) RNA testing. HIV RNA testing was the reference standard, with positive reference standard result defined as detectable HIV-1 RNA on an individual RNA test. Number and proportion with acute HIV infections detected. Among 86,836 participants with complete test results (median age, 29 years; 75.0% men; 51.8% men who have sex with men), established HIV infection was diagnosed in 1158 participants (1.33%) and acute HIV infection was diagnosed in 168 participants (0.19%). Acute HIV infection was detected in 134 participants with HIV Ag/Ab combination testing (0.15% [95% CI, 0.13%-0.18%]; sensitivity, 79.8% [95% CI, 72.9%-85.6%]; specificity, 99.9% [95% CI, 99.9%-99.9%]; positive predictive value, 59.0% [95% CI, 52.3%-65.5%]) and in 164 participants with pooled HIV RNA testing (0.19% [95% CI, 0.16%-0.22%]; sensitivity, 97.6% [95% CI, 94.0%-99.4%]; specificity, 100% [95% CI, 100%-100%]; positive predictive value, 96.5% [95% CI, 92.5%-98.7%]; sensitivity comparison, P testing detected 82% of acute HIV infections detectable by pooled HIV RNA testing. Compared with rapid HIV testing alone, HIV Ag/Ab combination testing increased the relative HIV diagnostic yield (both

  16. HIV/AIDS stigma and religiosity among African American women.

    Science.gov (United States)

    Muturi, Nancy; An, Soontae

    2010-06-01

    African American women are disproportionately affected by HIV/AIDS compared with other ethnicities, accounting for two-thirds (67%) of all women diagnosed with HIV. Despite their increased risk of HIV infection, few studies have been conducted to understand culture-specific factors leading to their vulnerability. Given the central role of religious organizations in African American communities, this study explored whether and to what extent religiosity plays a role in stigma toward HIV/AIDS. Results of hierarchical regression showed that after controlling for key factors, religiosity was a significant factor predicting the level of religious stigma. Those with high religiosity displayed significantly higher stigma, associating HIV/AIDS with a curse or punishment from God. Verbatim responses to an open-ended question also revealed seemingly ingrained prejudice against HIV/AIDS from a religious perspective. The findings point to the important role of faith-based organizations (FBOs) in addressing HIV/AIDS issues within African American communities.

  17. The next 5 years of global HIV/AIDS policy: critical gaps and strategies for effective responses.

    Science.gov (United States)

    Szekeres, Greg

    2008-08-01

    The University of California, Los Angeles Program in Global Health performed a landscape analysis based on interviews conducted between November 2006 and February 2007 with 35 key informants from major international organizations conducting HIV/AIDS work. Institutions represented included multilateral organizations, foundations, and governmental and non-governmental organizations. The purpose of this analysis is to assist major foundations and other institutions to understand better the international HIV/AIDS policy landscape and to formulate research and development programmes that can make a significant contribution to moving important issues forward in the HIV/AIDS policy arena. Topics identified during the interviews were organized around the four major themes of the Ford Foundation's Global HIV/AIDS Initiative: leadership and leadership development; equity; accountability; and global partnerships. Key informants focused on the need for a visionary response to the HIV pandemic, the need to maintain momentum, ways to improve the scope of leadership development programmes, ideas for improving gender equity and addressing regional disparities and the needs of vulnerable populations, recommendations for strengthening accountability mechanisms among governments, foundations, and civil society and on calling for increased collaboration and partnership among key players in the global HIV/AIDS response.

  18. HIV-1 accessory proteins VPR and Vif modulate antiviral response by targeting IRF-3 for degradation

    International Nuclear Information System (INIS)

    Okumura, Atsushi; Alce, Tim; Lubyova, Barbora; Ezelle, Heather; Strebel, Klaus; Pitha, Paula M.

    2008-01-01

    The activation of IRF-3 during the early stages of viral infection is critical for the initiation of the antiviral response; however the activation of IRF-3 in HIV-1 infected cells has not yet been characterized. We demonstrate that the early steps of HIV-1 infection do not lead to the activation and nuclear translocation of IRF-3; instead, the relative levels of IRF-3 protein are decreased due to the ubiquitin-associated proteosome degradation. Addressing the molecular mechanism of this effect we show that the degradation is independent of HIV-1 replication and that virion-associated accessory proteins Vif and Vpr can independently degrade IRF-3. The null mutation of these two genes reduced the capacity of the HIV-1 virus to down modulate IRF-3 levels. The degradation was associated with Vif- and Vpr-mediated ubiquitination of IRF-3 and was independent of the activation of IRF-3. N-terminal lysine residues were shown to play a critical role in the Vif- and Vpr-mediated degradation of IRF-3. These data implicate Vif and Vpr in the disruption of the initial antiviral response and point to the need of HIV-1 to circumvent the antiviral response during the very early phase of replication

  19. Antibody Responses with Fc-Mediated Functions after Vaccination of HIV-Infected Subjects with Trivalent Influenza Vaccine

    DEFF Research Database (Denmark)

    Kristensen, Anne B; Lay, William N; Ana-Sosa-Batiz, Fernanda

    2016-01-01

    to immunize this at-risk group. IMPORTANCE: Infection with HIV is associated with increasing disease severity following influenza infections, and annual influenza vaccinations are recommended for this target group. However, HIV-infected individuals respond relatively poorly to vaccination compared to healthy......This study seeks to assess the ability of seasonal trivalent inactivated influenza vaccine (TIV) to induce nonneutralizing antibodies (Abs) with Fc-mediated functions in HIV-uninfected and HIV-infected subjects. Functional influenza-specific Ab responses were studied in 30 HIV-negative and 27 HIV......-positive subjects immunized against seasonal influenza. All 57 subjects received the 2015 TIV. Fc-mediated antihemagglutinin (anti-HA) Ab activity was measured in plasma before and 4 weeks after vaccination using Fc-receptor-binding assays, NK cell activation assays, and phagocytosis assays. At baseline, the HIV...

  20. Cardiovascular risk prediction in HIV-infected patients: comparing the Framingham, atherosclerotic cardiovascular disease risk score (ASCVD), Systematic Coronary Risk Evaluation for the Netherlands (SCORE-NL) and Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) risk prediction models.

    Science.gov (United States)

    Krikke, M; Hoogeveen, R C; Hoepelman, A I M; Visseren, F L J; Arends, J E

    2016-04-01

    The aim of the study was to compare the predictions of five popular cardiovascular disease (CVD) risk prediction models, namely the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) model, the Framingham Heart Study (FHS) coronary heart disease (FHS-CHD) and general CVD (FHS-CVD) models, the American Heart Association (AHA) atherosclerotic cardiovascular disease risk score (ASCVD) model and the Systematic Coronary Risk Evaluation for the Netherlands (SCORE-NL) model. A cross-sectional design was used to compare the cumulative CVD risk predictions of the models. Furthermore, the predictions of the general CVD models were compared with those of the HIV-specific D:A:D model using three categories ( 20%) to categorize the risk and to determine the degree to which patients were categorized similarly or in a higher/lower category. A total of 997 HIV-infected patients were included in the study: 81% were male and they had a median age of 46 [interquartile range (IQR) 40-52] years, a known duration of HIV infection of 6.8 (IQR 3.7-10.9) years, and a median time on ART of 6.4 (IQR 3.0-11.5) years. The D:A:D, ASCVD and SCORE-NL models gave a lower cumulative CVD risk, compared with that of the FHS-CVD and FHS-CHD models. Comparing the general CVD models with the D:A:D model, the FHS-CVD and FHS-CHD models only classified 65% and 79% of patients, respectively, in the same category as did the D:A:D model. However, for the ASCVD and SCORE-NL models, this percentage was 89% and 87%, respectively. Furthermore, FHS-CVD and FHS-CHD attributed a higher CVD risk to 33% and 16% of patients, respectively, while this percentage was D:A:D, ASCVD and SCORE-NL models. This could have consequences regarding overtreatment, drug-related adverse events and drug-drug interactions. © 2015 British HIV Association.

  1. A critical historical analysis of the South African Catholic Church's HIV/AIDS response between 2000 and 2005.

    Science.gov (United States)

    Joshua, Stephen Muoki

    2010-12-01

    The South African HIV and AIDS experience is unique in many ways considering the country's delayed and robust epidemic, the apartheid context, and successive HIV-denialist government regimes. While the struggle for democracy may have overshadowed the enormity of the unfolding HIV epidemic, there was also a delay in constructive religious responses to it early on. In 1990, HIV/AIDS was declared a Catholic institutional focus, and by 2000 the Church had established the largest system of care and treatment in the country besides that of the government. However, the Catholic Church suffered severe criticism on account of its anti-condom policy to HIV prevention. As a result, the institutional Church underwent both organisational and ideological changes in an attempt to adapt to the contextual challenges brought about by HIV and AIDS. Informed by archival collections and oral sources, this article endeavours to critically analyse the HIV/AIDS-related care and treatment activities of the Catholic Church in South Africa between 2000 and 2005. It argues that the complex interplay between HIV and AIDS, the controversy about condom use, and the availability of antiretroviral therapy, accompanied by church activists' multiple engagements with these issues, changed the Church's institutional HIV/AIDS response at that time, in effect transforming the Catholic Church in South Africa into a substantial health asset and agent. However, its stance against the use of condoms for HIV prevention, informed by a larger religious tradition on sexuality, proved to be a health liability.

  2. Europe's Shifting Response to HIV/AIDS: From Human Rights to Risk Management.

    Science.gov (United States)

    Smith, Julia

    2016-12-01

    Despite a history of championing HIV/AIDS as a human rights issue, and a rhetorical commitment to health as a human right, European states and institutions have shifted from a rights-based response to a risk management approach to HIV/AIDS since the economic recession of 2008. An interdisciplinary perspective is applied to analyze health policy changes at the national, regional, and global levels by drawing on data from key informant interviews, and institutional and civil society documents. It is demonstrated that, in the context of austerity measures, member states such as the UK and Greece reduced commitments to rights associated with HIV/AIDS; at the regional level, the EU failed to develop rights-based approaches to address the vulnerabilities and health care needs of key populations affected by HIV/AIDS, particularly migrants and sex workers; and at the global level, the EU backtracked on commitments to global health and is prioritizing the intellectual property rights of pharmaceutical companies over the human rights of people living with HIV/AIDS. The focus within and from the EU is on containment, efficiency, and cost reduction. The rights of those most affected are no longer prioritized.

  3. Rapid selection of escape mutants by the first CD8 T cell responses in acute HIV-1 infection

    Energy Technology Data Exchange (ETDEWEB)

    Korber, Bette Tina Marie [Los Alamos National Laboratory

    2008-01-01

    The recent failure of a vaccine that primes T cell responses to control primary HIV-1 infection has raised doubts about the role of CD8+ T cells in early HIV-1 infection. We studied four patients who were identified shortly after HIV-1 infection and before seroconversion. In each patient there was very rapid selection of multiple HIV-1 escape mutants in the transmitted virus by CD8 T cells, including examples of complete fixation of non-synonymous substitutions within 2 weeks. Sequencing by single genome amplification suggested that the high rate of virus replication in acute infection gave a selective advantage to virus molecules that contained simultaneous and gained sequential T cell escape mutations. These observations show that whilst early HIV-1 specific CD8 T cells can act against virus, rapid escape means that these T cell responses are unlikely to benefit the patient and may in part explain why current HIV-1 T cell vaccines may not be protective.

  4. Human Resources Practitioners’ Perceptions Of Their Role And Responsibility In Managing HIV/Aids In Industry

    Directory of Open Access Journals (Sweden)

    C. DE W. van Wyk

    2006-11-01

    Full Text Available The central question to be examined revolved around an analysis of the perceptions of Human Resources Practitioners regarding their role and responsibility in the management of HIV/AIDS in industry. A convenience sample of HR Practitioners was used in a cross-sectional design. A questionnaire measuring the constructs of managing HIV/AIDS in industry, as well as a biographical questionnaire was administered. The questionnaire proved to be reliable. A Cronbach alpha coefficient of 0,82 and 0,71 was obtained. Descriptive statistics were used to analyse the data. Results indicated that HR Practitioners experienced and perceived significant differences with regard to the implementation of their companies’ policy formation and -implementation, training needs of managers and employees, mentoring/ coaching -approaches and other AIDS-related issues in terms of their perceptions regarding the management of HIV/AIDS. The findings revealed a gap of knowledge on managing HIV/AIDS existing among HR Practitioners at all levels. While some HR Practitioners had a detailed knowledge of the disease and its prevention, others were ignorant about it, but agreed that the management of HIV/AIDS can be seen as an integral part of their daily role and responsibility in industry. Recommendations were proposed for future research, policy making and practice in the area of HIV/AIDS and the management thereof.

  5. Interplay of HIV-1 phenotype and neutralizing antibody response in pathogenesis of AIDS.

    Science.gov (United States)

    Scarlatti, G; Leitner, T; Hodara, V; Jansson, M; Karlsson, A; Wahlberg, J; Rossi, P; Uhlén, M; Fenyö, E M; Albert, J

    1996-06-01

    A majority of human immunodeficiency virus type 1 (HIV-1) infected individuals display a rapid loss of CD4+ lymphocytes with fast progression towards overt acquired immunodeficiency syndrome (AIDS). However, a small proportion of individuals infected by HIV-1 remain immunologically intact for many years. In order to identify factors that might influence the pathogenesis of HIV-1 infection, 21 Italian mothers and 11 Swedish homosexual men were studied for the presence of autologous neutralizing antibodies in serum, biological phenotype of virus isolates and envelope variable region 3 (V3) sequences. The results were compared to the risk of mother-to-child transmission and progression of the disease. The presence of a neutralizing antibody response to the autologous virus as well as a virus with slow replicative capacity were linked both to low risk of mother-to-child transmission and non-progression of the disease. Patients whose peripheral blood mononuclear cells contained a mutation in the tip of the V3 loop (Arg318 to serine, lysine or leucine) significantly more often had neutralizing antibodies to autologous virus isolates containing arginine at this position. Thus, it appears that the interplay and balance between neutralizing antibody response of the host and the biological phenotype of HIV-1 strongly influence pathogenesis.

  6. Cellular Architecture of Spinal Granulomas and the Immunological Response in Tuberculosis Patients Coinfected with HIV.

    Science.gov (United States)

    Bhattacharya, Debapriya; Danaviah, Siva; Muema, Daniel M; Akilimali, Ngomu Akeem; Moodley, Prashini; Ndung'u, Thumbi; Das, Gobardhan

    2017-01-01

    Mycobacterium tuberculosis ( M.tb ) and HIV are individually responsible for the most deaths worldwide among all infectious agents, and coinfection with M.tb and HIV is a significant public health challenge in the developing world. Although the lung is the primary target organ for tuberculosis (TB), M.tb can also cause extrapulmonary tuberculosis (EPTB) such as in the bones and joints. Treatment of EPTB is much more challenging than treatment of pulmonary TB. The hallmark of the host immune response against TB is the formation of organized structures called granulomas that are infiltrated with immune cells and are rich in cytokines and chemokines. Inside granulomas, the host confines the M.tb bacteria to a particular region of the organ and avoids dispersion. In this study, we analyzed immune cells in bone granulomas of patients with EPTB that are also coinfected with HIV. We found that HIV-infected TB patients have dispersed bone granulomas, with reduced T cell numbers and a concomitant increase in plasma cells. Additionally, HIV-infected patients exhibited dramatically increased serum levels of IgM and IgG1 antibodies, which is indicative of T-cell-independent B-cell activation and mucosal T-cell activation, respectively. Interestingly, we also observed that CD29 + stem cells are increased in HIV-TB coinfection, suggesting a link with HIV infection. Therefore, our work provides new insights into the architecture of spinal TB granulomas and the role of B-cells and humoral immunity against a highly infectious intracellular pathogen. We propose that our findings will inform biomarker identification for EPTB and possibly the development of related therapeutics and/or vaccines to protect HIV-infected patients against disseminated TB.

  7. Evaluation of the genotypic prediction of HIV-1 coreceptor use versus a phenotypic assay and correlation with the virological response to maraviroc: the ANRS GenoTropism study.

    Science.gov (United States)

    Recordon-Pinson, Patricia; Soulié, Cathia; Flandre, Philippe; Descamps, Diane; Lazrek, Mouna; Charpentier, Charlotte; Montes, Brigitte; Trabaud, Mary-Anne; Cottalorda, Jacqueline; Schneider, Véronique; Morand-Joubert, Laurence; Tamalet, Catherine; Desbois, Delphine; Macé, Muriel; Ferré, Virginie; Vabret, Astrid; Ruffault, Annick; Pallier, Coralie; Raymond, Stéphanie; Izopet, Jacques; Reynes, Jacques; Marcelin, Anne-Geneviève; Masquelier, Bernard

    2010-08-01

    Genotypic algorithms for prediction of HIV-1 coreceptor usage need to be evaluated in a clinical setting. We aimed at studying (i) the correlation of genotypic prediction of coreceptor use in comparison with a phenotypic assay and (ii) the relationship between genotypic prediction of coreceptor use at baseline and the virological response (VR) to a therapy including maraviroc (MVC). Antiretroviral-experienced patients were included in the MVC Expanded Access Program if they had an R5 screening result with Trofile (Monogram Biosciences). V3 loop sequences were determined at screening, and coreceptor use was predicted using 13 genotypic algorithms or combinations of algorithms. Genotypic predictions were compared to Trofile; dual or mixed (D/M) variants were considered as X4 variants. Both genotypic and phenotypic results were obtained for 189 patients at screening, with 54 isolates scored as X4 or D/M and 135 scored as R5 with Trofile. The highest sensitivity (59.3%) for detection of X4 was obtained with the Geno2pheno algorithm, with a false-positive rate set up at 10% (Geno2pheno10). In the 112 patients receiving MVC, a plasma viral RNA load of <50 copies/ml was obtained in 68% of cases at month 6. In multivariate analysis, the prediction of the X4 genotype at baseline with the Geno2pheno10 algorithm including baseline viral load and CD4 nadir was independently associated with a worse VR at months 1 and 3. The baseline weighted genotypic sensitivity score was associated with VR at month 6. There were strong arguments in favor of using genotypic coreceptor use assays for determining which patients would respond to CCR5 antagonist.

  8. The influence of different helminth infection phenotypes on immune responses against HIV in co-infected adults in South Africa

    Directory of Open Access Journals (Sweden)

    Mabaso Musawenkosi LH

    2011-10-01

    Full Text Available Abstract Background The convergent distribution of the Human Immunodeficiency Virus (HIV and helminth infections has led to the suggestion that infection with helminths exacerbates the HIV epidemic in developing countries. In South Africa, it is estimated that 57% of the population lives in poverty and carries the highest burden of both HIV and helmith infections, however, the disease interactions are under-researched. Methods We employed both coproscopy and Ascaris lumbricoides-specific serum IgE to increase diagnostic sensitivity and to distinguish between different helminth infection phenotypes and their effects on immune responses in HIV co-infected individuals. Coproscopy was done by formol ether and Kato Katz methods. HIV positive and negative adults were stratified according to the presence or absence of A. lumbricoides and/or Trichuris trichuria eggs with or without elevated Ascaris IgE. Lymphocyte subsets were phenotyped by flow cytometry. Viral loads, serum total IgE and eosinophils were also analysed. Lymphocyte activation markers (CCR5, HLA-DR, CD25, CD38 and CD71 were determined. Non parametric statistics were used to describe differences in the variables between the subgroups. Results Helminth prevalence ranged between 40%-60%. Four distinct subgroups of were identified, and this included egg positive/high Ascaris-specific IgE (egg+IgEhi, egg positive/low IgE (egg+IgElo, egg negative/high IgE (egg-IgEhi and egg negative/low IgE (egg-IgElo individuals. The egg+IgEhi subgroup displayed lymphocytopenia, eosinophilia, (low CD4+ counts in HIV- group, high viral load (in HIV+ group, and an activated lymphocyte profile. High Ascaris IgE subgroups (egg+IgEhi and egg-IgEhi had eosinophilia, highest viral loads, and lower CD4+ counts in the HIV- group. Egg excretion and low IgE (egg+IgElo status demonstrated a modified Th2 immune profile with a relatively competent response to HIV. Conclusions People with both helminth egg excretion and high

  9. Predicted levels of HIV drug resistance

    DEFF Research Database (Denmark)

    Cambiano, Valentina; Bertagnolio, Silvia; Jordan, Michael R

    2014-01-01

    -term effects. METHODS: The previously validated HIV Synthesis model was calibrated to South Africa. Resistance was modeled at the level of single mutations, transmission potential, persistence, and effect on drug activity. RESULTS: We estimate 652 000 people (90% uncertainty range: 543 000-744 000) are living...... are maintained, in 20 years' time HIV incidence is projected to have declined by 22% (95% confidence interval, CI -23 to -21%), and the number of people carrying NNRTI resistance to be 2.9-fold higher. If enhancements in diagnosis and retention in care occur, and ART is initiated at CD4 cell count less than 500......  cells/μl, HIV incidence is projected to decline by 36% (95% CI: -37 to -36%) and the number of people with NNRTI resistance to be 4.1-fold higher than currently. Prevalence of people with viral load more than 500  copies/ml carrying NRMV is not projected to differ markedly according to future ART...

  10. Isotype Diversification of IgG Antibodies to HIV Gag Proteins as a Therapeutic Vaccination Strategy for HIV Infection.

    Science.gov (United States)

    French, Martyn A; Abudulai, Laila N; Fernandez, Sonia

    2013-08-09

    The development of vaccines to treat and prevent human immunodeficiency virus (HIV) infection has been hampered by an incomplete understanding of "protective" immune responses against HIV. Natural control of HIV-1 infection is associated with T-cell responses against HIV-1 Gag proteins, particularly CD8⁺ T-cell responses restricted by "protective" HLA-B alleles, but other immune responses also contribute to immune control. These immune responses appear to include IgG antibodies to HIV-1 Gag proteins, interferon-a-dependant natural killer (NK) cell responses and plasmacytoid dendritic cell (pDC) responses. Here, it is proposed that isotype diversification of IgG antibodies against HIV-1 Gag proteins, to include IgG2, as well as IgG3 and IgG1 antibodies, will broaden the function of the antibody response and facilitate accessory cell responses against HIV-1 by NK cells and pDCs. We suggest that this should be investigated as a vaccination strategy for HIV-1 infection.

  11. Isotype Diversification of IgG Antibodies to HIV Gag Proteins as a Therapeutic Vaccination Strategy for HIV Infection

    Directory of Open Access Journals (Sweden)

    Sonia Fernandez

    2013-08-01

    Full Text Available The development of vaccines to treat and prevent human immunodeficiency virus (HIV infection has been hampered by an incomplete understanding of “protective” immune responses against HIV. Natural control of HIV-1 infection is associated with T-cell responses against HIV-1 Gag proteins, particularly CD8+ T-cell responses restricted by “protective” HLA-B alleles, but other immune responses also contribute to immune control. These immune responses appear to include IgG antibodies to HIV-1 Gag proteins, interferon-a-dependant natural killer (NK cell responses and plasmacytoid dendritic cell (pDC responses. Here, it is proposed that isotype diversification of IgG antibodies against HIV-1 Gag proteins, to include IgG2, as well as IgG3 and IgG1 antibodies, will broaden the function of the antibody response and facilitate accessory cell responses against HIV-1 by NK cells and pDCs. We suggest that this should be investigated as a vaccination strategy for HIV-1 infection.

  12. Transient elastography for predicting liver-related events in cirrhotic HIV-infected patients

    OpenAIRE

    Montes-Ramírez, M. L.; Berenguer, Juan; Miró, J. M.; Quereda, Carmen; Hernando Jeréz, María Asunción; Sanz, J.; Ortega, E.; Tural, Cristina; Wichmann, M. A.; Zamora, F. X.; González García, J. J.

    2017-01-01

    We assessed liver stiffness measurement (LSM) for the prediction of mortality and decompensation in HIVinfected patients with compensated liver cirrhosis. A prospective cohort study of HIV-infected patients with confirmed liver cirrhosis from 9 hospitals in Spain. LSM was undertaken for each patient; clinical events were collected prospectively after the baseline visit, and patients were followed until death or the censoring date. We used univariate/multivariate Cox proportional haz...

  13. HIV Molecular Immunology 2015

    Energy Technology Data Exchange (ETDEWEB)

    Yusim, Karina [Los Alamos National Lab. (LANL), Los Alamos, NM (United States). Theoretical Division; Korber, Bette Tina [Los Alamos National Lab. (LANL), Los Alamos, NM (United States). Theoretical Division; Brander, Christian [Institucio Catalana de Recerca i Estudis Avancats (ICREA), Barcelona (Spain); Barouch, Dan [Beth Israel Deaconess Medical Center, Boston, MA (United States). Division of Vaccine Research; de Boer, Rob [Utrecht University, Utrecht (Netherlands). Faculty of Biology; Haynes, Barton F. [Duke Univ., Durham, NC (United States). Duke Human Vaccine Institute and Departments of Medicine, Surgery and Immunology; Koup, Richard [National Inst. of Health (NIH), Bethesda, MD (United States). Vaccine Research Center; Moore, John P. [Cornell Univ., Ithaca, NY (United States). Weill Medical College; Walker, Bruce D. [Ragon Institute, Cambridge, MA (United States); Watkins, David [Wisconsin Regional Primate Research Center, Madison, WI (United States)

    2016-04-05

    The scope and purpose of the HIV molecular immunology database: HIV Molecular Immunology is a companion volume to HIV Sequence Compendium. This publication, the 2015 edition, is the PDF version of the web-based HIV Immunology Database (http://www.hiv.lanl.gov/ content/immunology/). The web interface for this relational database has many search options, as well as interactive tools to help immunologists design reagents and interpret their results. In the HIV Immunology Database, HIV-specific B-cell and T-cell responses are summarized and annotated. Immunological responses are divided into three parts, CTL, T helper, and antibody. Within these parts, defined epitopes are organized by protein and binding sites within each protein, moving from left to right through the coding regions spanning the HIV genome. We include human responses to natural HIV infections, as well as vaccine studies in a range of animal models and human trials. Responses that are not specifically defined, such as responses to whole proteins or monoclonal antibody responses to discontinuous epitopes, are summarized at the end of each protein section. Studies describing general HIV responses to the virus, but not to any specific protein, are included at the end of each part. The annotation includes information such as cross-reactivity, escape mutations, antibody sequence, TCR usage, functional domains that overlap with an epitope, immune response associations with rates of progression and therapy, and how specific epitopes were experimentally defined. Basic information such as HLA specificities for T-cell epitopes, isotypes of monoclonal antibodies, and epitope sequences are included whenever possible. All studies that we can find that incorporate the use of a specific monoclonal antibody are included in the entry for that antibody. A single T-cell epitope can have multiple entries, generally one entry per study. Finally, maps of all defined linear epitopes relative to the HXB2 reference proteins

  14. Predicting risk of cancer during HIV infection

    DEFF Research Database (Denmark)

    Borges, Álvaro H; Silverberg, Michael J; Wentworth, Deborah

    2013-01-01

    To investigate the relationship between inflammatory [interleukin-6 (IL-6) and C-reactive protein (CRP)] and coagulation (D-dimer) biomarkers and cancer risk during HIV infection.......To investigate the relationship between inflammatory [interleukin-6 (IL-6) and C-reactive protein (CRP)] and coagulation (D-dimer) biomarkers and cancer risk during HIV infection....

  15. Comparison of HIV-1 genotypic resistance test interpretation systems in predicting virological outcomes over time

    NARCIS (Netherlands)

    D. Frentz (Dineke); C.A.B. Boucher (Charles); M. Assel (Matthias); A. de Luca (Andrea); M. Fabbiani (Massimiliano); F. Incardona (Francesca); P. Libin (Pieter); N. Manca (Nino); V. Müller (Viktor); B.O. Nualláin (Breanndán); R. Paredes (Roger); M. Prosperi (Mattia); E. Quiros-Roldan (Eugenia); L. Ruiz (Lidia); P.M.A. Sloot (Peter); C. Torti (Carlo); A.M. Vandamme (Anne Mieke); K. Laethem (Kristel); M. Zazzi (Maurizio); D.A.M.C. van de Vijver (David)

    2010-01-01

    textabstractBackground: Several decision support systems have been developed to interpret HIV-1 drug resistance genotyping results. This study compares the ability of the most commonly used systems (ANRS, Rega, and Stanford's HIVdb) to predict virological outcome at 12, 24, and 48 weeks.

  16. Financing the HIV response in sub-Saharan Africa from domestic sources: Moving beyond a normative approach.

    Science.gov (United States)

    Remme, Michelle; Siapka, Mariana; Sterck, Olivier; Ncube, Mthuli; Watts, Charlotte; Vassall, Anna

    2016-11-01

    Despite optimism about the end of AIDS, the HIV response requires sustained financing into the future. Given flat-lining international aid, countries' willingness and ability to shoulder this responsibility will be central to access to HIV care. This paper examines the potential to expand public HIV financing, and the extent to which governments have been utilising these options. We develop and compare a normative and empirical approach. First, with data from the 14 most HIV-affected countries in sub-Saharan Africa, we estimate the potential increase in public HIV financing from economic growth, increased general revenue generation, greater health and HIV prioritisation, as well as from more unconventional and innovative sources, including borrowing, health-earmarked resources, efficiency gains, and complementary non-HIV investments. We then adopt a novel empirical approach to explore which options are most likely to translate into tangible public financing, based on cross-sectional econometric analyses of 92 low and middle-income country governments' most recent HIV expenditure between 2008 and 2012. If all fiscal sources were simultaneously leveraged in the next five years, public HIV spending in these 14 countries could increase from US$3.04 to US$10.84 billion per year. This could cover resource requirements in South Africa, Botswana, Namibia, Kenya, Nigeria, Ethiopia, and Swaziland, but not even half the requirements in the remaining countries. Our empirical results suggest that, in reality, even less fiscal space could be created (a reduction by over half) and only from more conventional sources. International financing may also crowd in public financing. Most HIV-affected lower-income countries in sub-Saharan Africa will not be able to generate sufficient public resources for HIV in the medium-term, even if they take very bold measures. Considerable international financing will be required for years to come. HIV funders will need to engage with broader

  17. Iowa Gambling Task performance and emotional distress interact to predict risky sexual behavior in individuals with dual substance and HIV diagnoses

    Science.gov (United States)

    Wardle, Margaret C.; Gonzalez, Raul; Bechara, Antoine; Martin-Thormeyer, Eileen M.

    2013-01-01

    HIV+ substance-dependent individuals (SDIs) show emotional distress and executive impairment, but in isolation these poorly predict sexual risk. We hypothesized that an executive measure sensitive to emotional aspects of judgment (Iowa Gambling Task; IGT) would identify HIV+ SDIs whose sexual risks were influenced by emotional distress. We assessed emotional distress and performance on several executive tasks in 190 HIV+ SDIs. IGT performance interacted significantly with emotional distress, such that only in better performers were distress and risk related. Our results are interpreted using the somatic marker hypothesis and indicate that the IGT identifies HIV+ SDIs for whom psychological distress influences HIV risk. PMID:20480423

  18. Clinical prediction and diagnosis of neurosyphilis in HIV-infected patients with early Syphilis.

    Science.gov (United States)

    Dumaresq, Jeannot; Langevin, Stéphanie; Gagnon, Simon; Serhir, Bouchra; Deligne, Benoît; Tremblay, Cécile; Tsang, Raymond S W; Fortin, Claude; Coutlée, François; Roger, Michel

    2013-12-01

    The diagnosis of neurosyphilis (NS) is a challenge, especially in HIV-infected patients, and the criteria for deciding when to perform a lumbar puncture (LP) in HIV-infected patients with syphilis are controversial. We retrospectively reviewed demographic, clinical, and laboratory data from 122 cases of HIV-infected patients with documented early syphilis who underwent an LP to rule out NS, and we evaluated 3 laboratory-developed validated real-time PCR assays, the Treponema pallidum particle agglutination (TPPA) assay, the fluorescent treponemal antibody absorption (FTA-ABS) assay, and the line immunoassay INNO-LIA Syphilis, for the diagnosis of NS from cerebrospinal fluid (CSF) samples of these patients. NS was defined by a reactive CSF-VDRL test result and/or a CSF white blood cell (WBC) count of >20 cells/μl. Thirty of the 122 patients (24.6%) had early NS. Headache, visual symptoms, a CD4 cell count of FTA-ABS, TPPA, and INNO-LIA assays had sensitivities of 58%, 100%, 68%, and 100%, specificities of 67%, 12%, 49%, and 13%, and negative predictive values of 85%, 100%, 84%, and 100%, respectively. Visual disturbances, headache, uncontrolled HIV-1 viremia, and a CD4 cell count of <500 cells/μl were predictors of NS in HIV-infected patients with early syphilis, while blood serum RPR titers were not; therefore, RPR titers should not be used as the sole criterion for deciding whether to perform an LP in early syphilis. When applied to CSF samples, the INNO-LIA Syphilis assay easily helped rule out NS.

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

    Science.gov (United States)

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

    2012-01-01

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

  20. Black churches and HIV/AIDS: factors influencing congregations’ responsiveness to social issues.

    Science.gov (United States)

    Fulton, Brad R

    2011-01-01

    The ambivalent response of many black churches to current social issues has caused some scholars to question the centrality of black churches within African-American communities. Using a nationally representative sample of black congregations, this study engages the debate about the institutional centrality of black churches by focusing on their response to HIV/AIDS. Although many congregational studies treat black churches as a monolithic whole, this analysis identifies heterogeneity among black churches that shapes their responsiveness to social issues. Contrary to prior claims, a congregation's liberal-conservative ideological orientation does not significantly affect its likelihood of having an HIV/AIDS program. Beyond assessing churches’ internal characteristics, this study uses institutional theory to analyze churches as open systems that can be influenced by their surrounding environment. It demonstrates that externally engaged congregations are significantly more likely to have a program. These results indicate that black churches maintain institutional centrality by engaging their external environment.

  1. Evolution of the health sector response to HIV in Myanmar: progress, challenges and the way forward.

    Science.gov (United States)

    Oo, Htun Nyunt; Hone, San; Fujita, Masami; Maw-Naing, Amaya; Boonto, Krittayawan; Jacobs, Marjolein; Phyu, Sabe; Bollen, Phavady; Cheung, Jacquie; Aung, Htin; Aung Sang, May Thu; Myat Soe, Aye; Pendse, Razia; Murphy, Eamonn

    2016-11-28

    Critical building blocks for the response to HIV were made until 2012 despite a series of political, social and financial challenges. A rapid increase of HIV service coverage was observed from 2012 to 2015 through collaborative efforts of government and non-governmental organisations (NGOs). Government facilities, in particular, demonstrated their capacity to expand services for antiretroviral therapy (ART), prevention of mother-to-child transmission (PMTCT) of HIV, tuberculosis and HIV co-infection and methadone-maintenance therapy (MMT). After nearly three decades into the response to HIV, Myanmar has adopted strategies to provide the right interventions to the right people in the right places to maximise impact and cost efficiency. In particular, the country is now using strategic information to classify areas into high-, medium- and low-HIV burden and risk of new infections for geographical prioritisation - as HIV remains concentrated among key population (KP) groups in specific geographical areas. Ways forward include: •Addressing structural barriers for KP to access services, and identifying and targeting KPs at higher risk;•Strengthening the network of public facilities, NGOs and general practitioners and introducing a case management approach to assist KPs and other clients with unknown HIV status, HIV-negative clients and newly diagnosed clients to access the health services across the continuum to increase the number of people testing for HIV and to reduce loss to follow-up in both prevention and treatment;•Increasing the availability of HIV testing and counselling services for KPs, clients of female sex workers (FSW), and other populations at risk, and raising the demand for timely testing including expansion of outreach and client-initiated voluntary counselling and testing (VCT) services;•Monitoring and maximising retention from HIV diagnosis to ART initiation and expanding quality HIV laboratory services, especially viral load

  2. Sequential Dysfunction and Progressive Depletion of Candida albicans-Specific CD4 T Cell Response in HIV-1 Infection

    Science.gov (United States)

    Liu, Fengliang; Fan, Xiuzhen; Auclair, Sarah; Ferguson, Monique; Sun, Jiaren; Soong, Lynn; Hou, Wei; Redfield, Robert R.; Birx, Deborah L.; Ratto-Kim, Silvia; Robb, Merlin L.; Kim, Jerome H.; Michael, Nelson L.; Hu, Haitao

    2016-01-01

    Loss of immune control over opportunistic infections can occur at different stages of HIV-1 (HIV) disease, among which mucosal candidiasis caused by the fungal pathogen Candida albicans (C. albicans) is one of the early and common manifestations in HIV-infected human subjects. The underlying immunological basis is not well defined. We have previously shown that compared to cytomegalovirus (CMV)-specific CD4 cells, C. albicans-specific CD4 T cells are highly permissive to HIV in vitro. Here, based on an antiretroviral treatment (ART) naïve HIV infection cohort (RV21), we investigated longitudinally the impact of HIV on C. albicans- and CMV-specific CD4 T-cell immunity in vivo. We found a sequential dysfunction and preferential depletion for C. albicans-specific CD4 T cell response during progressive HIV infection. Compared to Th1 (IFN-γ, MIP-1β) functional subsets, the Th17 functional subsets (IL-17, IL-22) of C. albicans-specific CD4 T cells were more permissive to HIV in vitro and impaired earlier in HIV-infected subjects. Infection history analysis showed that C. albicans-specific CD4 T cells were more susceptible to HIV in vivo, harboring modestly but significantly higher levels of HIV DNA, than CMV-specific CD4 T cells. Longitudinal analysis of HIV-infected individuals with ongoing CD4 depletion demonstrated that C. albicans-specific CD4 T-cell response was preferentially and progressively depleted. Taken together, these data suggest a potential mechanism for earlier loss of immune control over mucosal candidiasis in HIV-infected patients and provide new insights into pathogen-specific immune failure in AIDS pathogenesis. PMID:27280548

  3. Durability of response to vaccination against viral hepatitis A in HIV-infected patients: a 5-year observation.

    Science.gov (United States)

    Jabłonowska, E; Kuydowicz, J

    2014-09-01

    The aim of this study was to estimate the prevalence of total antibodies to hepatitis A virus (anti-HAV-T) in the group of HIV-positive adults in Lodz region of Poland, and to evaluate the response and long-term immunity after vaccination against hepatitis A virus. In the group of 234 HIV-infected patients, 72 persons (30.8%) were anti-HAV-T positive (>20 IU/L). In multivariate analysis, two independent factors associated with the presence of anti-HAV-T were identified: the age of patients (OR = 1.07) and the presence of antibodies to hepatitis C virus (OR = 2.87). Vaccination was completed in 83 patients. Good response (anti-HAV-T >20 IU/L one month after the booster dose) was obtained in 79.5% of patients. In patients with CD4 >200 cells/µL in multivariate analysis only presence of antibodies to hepatitis C virus was a prognostic factor for the response to vaccination (OR = 0.13). Among responders available for the follow-up, 82% (50 out of 61) had detectable anti-HAV-T at 1 year and 75.5% (37 out of 49) at 5 years. Our results demonstrate that most of the studied HIV-positive patients were susceptible to hepatitis A virus infection. Most HIV-infected adults with high CD4 counts had a durable response even up to 5 years after vaccination. Patients with a HIV/hepatitis C virus coinfection displayed a worse response to vaccination. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

  4. A consistency-based feature selection method allied with linear SVMs for HIV-1 protease cleavage site prediction.

    Directory of Open Access Journals (Sweden)

    Orkun Oztürk

    Full Text Available BACKGROUND: Predicting type-1 Human Immunodeficiency Virus (HIV-1 protease cleavage site in protein molecules and determining its specificity is an important task which has attracted considerable attention in the research community. Achievements in this area are expected to result in effective drug design (especially for HIV-1 protease inhibitors against this life-threatening virus. However, some drawbacks (like the shortage of the available training data and the high dimensionality of the feature space turn this task into a difficult classification problem. Thus, various machine learning techniques, and specifically several classification methods have been proposed in order to increase the accuracy of the classification model. In addition, for several classification problems, which are characterized by having few samples and many features, selecting the most relevant features is a major factor for increasing classification accuracy. RESULTS: We propose for HIV-1 data a consistency-based feature selection approach in conjunction with recursive feature elimination of support vector machines (SVMs. We used various classifiers for evaluating the results obtained from the feature selection process. We further demonstrated the effectiveness of our proposed method by comparing it with a state-of-the-art feature selection method applied on HIV-1 data, and we evaluated the reported results based on attributes which have been selected from different combinations. CONCLUSION: Applying feature selection on training data before realizing the classification task seems to be a reasonable data-mining process when working with types of data similar to HIV-1. On HIV-1 data, some feature selection or extraction operations in conjunction with different classifiers have been tested and noteworthy outcomes have been reported. These facts motivate for the work presented in this paper. SOFTWARE AVAILABILITY: The software is available at http

  5. HIV Risk Behavior and Access to Services: What Predicts HIV Testing among Heterosexually Active Homeless Men?

    Science.gov (United States)

    Wenzel, Suzanne L.; Rhoades, Harmony; Tucker, Joan S.; Golinelli, Daniela; Kennedy, David P.; Zhou, Annie; Ewing, Brett

    2012-01-01

    HIV is a serious epidemic among homeless persons, where rates of infection are estimated to be three times higher than in the general population. HIV testing is an effective tool for reducing HIV transmission and for combating poor HIV/AIDS health outcomes that disproportionately affect homeless persons, however, little is known about the HIV…

  6. HIV Molecular Immunology 2014

    Energy Technology Data Exchange (ETDEWEB)

    Yusim, Karina [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Korber, Bette Tina Marie [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Barouch, Dan [Beth Israel Deaconess Medical Center, Boston, MA (United States); Koup, Richard [Vaccine Research Center National Institutes of Health (United States); de Boer, Rob [Utrecht Univ. (Netherlands). Dept. of Biology; Moore, John P. [Cornell Univ., Ithaca, NY (United States). Weill Medical College; Brander, Christian [Institucioi Catalana de Recerca i Estudis Avancats (ICREA), Barcelona (Spain); Haynes, Barton F. [Duke Univ., Durham, NC (United States). Duke Human Vaccine Institute and Departments of Medicine, Surgery and Immunology; Walker, Bruce D. [Ragon Institute of Massachusetts General Hospital, Cambridge, MA (United States); Harvard Univ., Cambridge, MA (United States); Massachusetts Inst. of Technology (MIT), Cambridge, MA (United States)

    2015-02-03

    HIV Molecular Immunology is a companion volume to HIV Sequence Compendium. This publication, the 2014 edition, is the PDF version of the web-based HIV Immunology Database (http://www.hiv.lanl.gov/content/immunology/). The web interface for this relational database has many search options, as well as interactive tools to help immunologists design reagents and interpret their results. In the HIV Immunology Database, HIV-specific B-cell and T-cell responses are summarized and annotated. Immunological responses are divided into three parts, CTL, T helper, and antibody. Within these parts, defined epitopes are organized by protein and binding sites within each protein, moving from left to right through the coding regions spanning the HIV genome. We include human responses to natural HIV infections, as well as vaccine studies in a range of animal models and human trials. Responses that are not specifically defined, such as responses to whole proteins or monoclonal antibody responses to discontinuous epitopes, are summarized at the end of each protein section. Studies describing general HIV responses to the virus, but not to any specific protein, are included at the end of each part. The annotation includes information such as crossreactivity, escape mutations, antibody sequence, TCR usage, functional domains that overlap with an epitope, immune response associations with rates of progression and therapy, and how specific epitopes were experimentally defined. Basic information such as HLA specificities for T-cell epitopes, isotypes of monoclonal antibodies, and epitope sequences are included whenever possible. All studies that we can find that incorporate the use of a specific monoclonal antibody are included in the entry for that antibody. A single T-cell epitope can have multiple entries, generally one entry per study. Finally, maps of all defined linear epitopes relative to the HXB2 reference proteins are provided.

  7. Mapping MOS-HIV to HUI3 and EQ-5D-3L in Patients With HIV

    Directory of Open Access Journals (Sweden)

    Vilija R. Joyce MS

    2017-07-01

    Full Text Available Objectives: The Medical Outcomes Study HIV Health Survey (MOS-HIV is frequently used in HIV clinical trials; however, scores generated from the MOS-HIV are not suited for cost-effectiveness analyses as they do not assign utility values to health states. Our objective was to estimate and externally validate several mapping algorithms to predict Health Utilities Index Mark 3 (HUI3 and EQ-5D-3L utility values from the MOS-HIV. Methods: We developed and validated mapping algorithms using data from two HIV clinical trials. Data from the first trial (n = 367 formed the estimation data set for the HUI3 (4,610 observations and EQ-5D-3L (4,662 observations mapping algorithms; data from the second trial (n = 168 formed the HUI3 (1,135 observations and EQ-5D-3L (1,152 observations external validation data set. We compared ordinary least squares (OLS models of increasing complexity with the more flexible two-part, beta regression, and finite mixture models. We assessed model performance using mean absolute error (MAE and mean squared error (MSE. Results: The OLS model that used MOS-HIV dimension scores along with squared terms gave the best HUI3 predictions (mean observed 0.84; mean predicted 0.80; MAE 0.0961; the finite mixture model gave the best EQ-5D-3L predictions (mean observed 0.90; mean predicted 0.88; MAE 0.0567. All models produced higher prediction errors at the lower end of the HUI3 and EQ-5D-3L score ranges (<0.40. Conclusions: The proposed mapping algorithms can be used to predict HUI3 and EQ-5D-3L utility values from the MOS-HIV, although greater error may pose a problem in samples where a substantial proportion of patients are in poor health. These algorithms may be useful for estimating utility values from the MOS-HIV for cost-effectiveness studies when HUI3 or EQ-5D-3L data are not available.

  8. HIV-specific Fc effector function early in infection predicts the development of broadly neutralizing antibodies.

    Science.gov (United States)

    Richardson, Simone I; Chung, Amy W; Natarajan, Harini; Mabvakure, Batsirai; Mkhize, Nonhlanhla N; Garrett, Nigel; Abdool Karim, Salim; Moore, Penny L; Ackerman, Margaret E; Alter, Galit; Morris, Lynn

    2018-04-01

    While the induction of broadly neutralizing antibodies (bNAbs) is a major goal of HIV vaccination strategies, there is mounting evidence to suggest that antibodies with Fc effector function also contribute to protection against HIV infection. Here we investigated Fc effector functionality of HIV-specific IgG plasma antibodies over 3 years of infection in 23 individuals, 13 of whom developed bNAbs. Antibody-dependent cellular phagocytosis (ADCP), complement deposition (ADCD), cellular cytotoxicity (ADCC) and cellular trogocytosis (ADCT) were detected in almost all individuals with levels of activity increasing over time. At 6 months post-infection, individuals with bNAbs had significantly higher levels of ADCD and ADCT that correlated with antibody binding to C1q and FcγRIIa respectively. In addition, antibodies from individuals with bNAbs showed more IgG subclass diversity to multiple HIV antigens which also correlated with Fc polyfunctionality. Germinal center activity represented by CXCL13 levels and expression of activation-induced cytidine deaminase (AID) was found to be associated with neutralization breadth, Fc polyfunctionality and IgG subclass diversity. Overall, multivariate analysis by random forest classification was able to group bNAb individuals with 85% sensitivity and 80% specificity based on the properties of their antibody Fc early in HIV infection. Thus, the Fc effector function profile predicted the development of neutralization breadth in this cohort, suggesting that intrinsic immune factors within the germinal center provide a mechanistic link between the Fc and Fab of HIV-specific antibodies.

  9. Use of competitive polymerase chain reaction to determine HIV-1 levels in response to antiviral treatments

    NARCIS (Netherlands)

    Bruisten, S. M.; Koppelman, M. H.; Roos, M. T.; Loeliger, A. E.; Reiss, P.; Boucher, C. A.; Huisman, H. G.

    1993-01-01

    OBJECTIVE: To develop a competitive polymerase chain reaction technique with which to evaluate the usefulness of HIV-1 level as a marker of response to antiviral treatment. DESIGN: HIV-1 sequences were assessed by competitive polymerase chain reaction in four subjects participating in a double-blind

  10. Hyaluronic acid levels predict risk of hepatic encephalopathy and liver-related death in HIV/viral hepatitis coinfected patients

    DEFF Research Database (Denmark)

    Peters, Lars; Mocroft, Amanda; Soriano, Vincent

    2013-01-01

    Whereas it is well established that various soluble biomarkers can predict level of liver fibrosis, their ability to predict liver-related clinical outcomes is less clearly established, in particular among HIV/viral hepatitis co-infected persons. We investigated plasma hyaluronic acid's (HA......) ability to predict risk of liver-related events (LRE; hepatic coma or liver-related death) in the EuroSIDA study....

  11. The immunological response to syphilis differs by HIV status; a prospective observational cohort study.

    Science.gov (United States)

    Kenyon, Chris; Osbak, Kara Krista; Crucitti, Tania; Kestens, Luc

    2017-01-31

    It is not known if there is a difference in the immune response to syphilis between HIV-infected and uninfected individuals. We prospectively recruited all patients with a new diagnosis of syphilis and tested their plasma for IFNα, IFNγ, IL-1β, IL-12p40, IL-12p70, IP-10, MCP-1, MIP-1α, MIP-1β, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10 and IL-17A at baseline pre-treatment and 6 months following therapy. A total of 79 HIV-infected [44 primary/secondary syphilis (PSS) and 35 latent syphilis (LS)] and 12 HIV-uninfected (10 PSS and 2 LS) cases of syphilis and 30 HIV-infected controls were included in the study. At the baseline visit, compared to the control group, concentrations of IL-10 were significantly elevated in the HIV-infected and uninfected groups. The level of IL-10 was significantly higher in the HIV-infected compared to the HIV-uninfected PSS group (25.3 pg/mL (IQR, 4.56-41.76) vs 2.73 pg/mL (IQR, 1.55-9.02), P = 0.0192). In the HIV-infected PSS group (but not the HIV-infected LS or HIV-uninfected PSS groups) the IP-10, MIP-1b, IL-6 and IL-8 were raised compared to the controls. IL-10 levels decreased but did not return to control baseline values by 6 months in HIV infected PSS and LS and HIV uninfected PSS. PSS and LS in HIV-infected individuals is characterized by an increase in inflammatory and anti-inflammatory cytokines such as IL-10. The increase of IL-10 is greater in HIV-infected than uninfected individuals. Further work is required to ascertain if this is part of an immunological profile that correlates with adverse outcomes such as serofast syphilis and neurosyphilis, in HIV-infected individuals.

  12. HIV-1 with multiple CCR5/CXCR4 chimeric receptor use is predictive of immunological failure in infected children.

    Science.gov (United States)

    Cavarelli, Mariangela; Karlsson, Ingrid; Zanchetta, Marisa; Antonsson, Liselotte; Plebani, Anna; Giaquinto, Carlo; Fenyö, Eva Maria; De Rossi, Anita; Scarlatti, Gabriella

    2008-09-29

    HIV-1 R5 viruses are characterized by a large phenotypic variation, that is reflected by the mode of coreceptor use. The ability of R5 HIV-1 to infect target cells expressing chimeric receptors between CCR5 and CXCR4 (R5(broad) viruses), was shown to correlate with disease stage in HIV-1 infected adults. Here, we ask the question whether phenotypic variation of R5 viruses could play a role also in mother-to-child transmission (MTCT) of HIV-1 and pediatric disease progression. Viral isolates obtained from a total of 59 HIV-1 seropositive women (24 transmitting and 35 non transmitting) and 28 infected newborn children, were used to infect U87.CD4 cells expressing wild type or six different CCR5/CXCR4 chimeric receptors. HIV-1 isolates obtained from newborn infants had predominantly R5(narrow) phenotype (n = 20), but R5(broad) and R5X4 viruses were also found in seven and one case, respectively. The presence of R5(broad) and R5X4 phenotypes correlated significantly with a severe decline of the CD4+ T cells (CDC stage 3) or death within 2 years of age. Forty-three percent of the maternal R5 isolates displayed an R5(broad) phenotype, however, the presence of the R5(broad) virus was not predictive for MTCT of HIV-1. Of interest, while only 1 of 5 mothers with an R5X4 virus transmitted the dualtropic virus, 5 of 6 mothers carrying R5(broad) viruses transmitted viruses with a similar broad chimeric coreceptor usage. Thus, the maternal R5(broad) phenotype was largely preserved during transmission and could be predictive of the phenotype of the newborn's viral variant. Our results show that R5(broad) viruses are not hampered in transmission. When transmitted, immunological failure occurs earlier than in children infected with HIV-1 of R5(narrow) phenotype. We believe that this finding is of utmost relevance for therapeutic interventions in pediatric HIV-1 infection.

  13. Delbruck Prize Award: Insights into HIV Dynamics and Cure

    Science.gov (United States)

    Perelson, Alan S.

    A large effort is being made to find a means to cure HIV infection. I will present a dynamical model of a phenomenon called post-treatment control (PTC) or functional cure of HIV-infection in which some patients treated with suppressive antiviral therapy have been taken off of therapy and then spontaneously control HIV infection. The model relies on an immune response and bistability to explain PTC. I will then generalize the model to explicitly include immunotherapy with monoclonal antibodies approved for use in cancer to show that one can induce PTC with a limited number of antibody infusions and compare model predictions with experiments in SIV infected macaques given immunotherapy. Lastly, I will argue that quantitative insights derived from models of HIV infection have and will continue to play an important role in medicine.

  14. An assessment of government policy response to HIV/AIDS in Ghana

    African Journals Online (AJOL)

    emphasis on the linkages between economic development, urban ... of policy response by counter-balancing the level of .... show high prevalence in the eastern and Volta regions ..... subjects such as English language, agriculture, life skills, ..... Work! USAID/Mobile Task Team on HIV/AIDS in Education,Accra. Claypoole, C.

  15. Antibody Response is More Likely to Pneumococcal Proteins Than to Polysaccharide After HIV-associated Invasive Pneumococcal Disease

    DEFF Research Database (Denmark)

    Kantsø, Bjørn; Green, Nicola; Goldblatt, David

    2015-01-01

    to at least 1 protein compared to 51% of non-IPD controls. HIV IPD cases responded to more proteins than non-IPD controls (8.6 ± 8.4 vs 4.2 ± 7.6 proteins; P = .01), and had a significantly higher probability of yielding an antibody response to the proteins PiaA, PsaA, and PcpA. Twenty-two percent of HIV......-infected individuals with IPD had a serotype-specific antibody response. Younger age at the time of IPD was the only predictor of a serotype-specific pneumococcal antibody response, whereas we did not identify predictors of a protein-specific antibody response. CONCLUSIONS: Antibody responses occurred more frequently...

  16. Cardiovascular disease (CVD) and chronic kidney disease (CKD) event rates in HIV-positive persons at high predicted CVD and CKD risk

    DEFF Research Database (Denmark)

    Boyd, Mark A; Mocroft, Amanda; Ryom, Lene

    2017-01-01

    BACKGROUND: The Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) study has developed predictive risk scores for cardiovascular disease (CVD) and chronic kidney disease (CKD, defined as confirmed estimated glomerular filtration rate [eGFR] ≤ 60 ml/min/1.73 m2) events in HIV...

  17. "They make money off of us": a phenomenological analysis of consumer perceptions of corruption in Kenya's HIV response system.

    Science.gov (United States)

    Kagotho, Njeri; Bunger, Alicia; Wagner, Kristen

    2016-09-05

    Problems with misallocation and redirection of critical resources and benefits intended for PLHIV are not uncommon in Kenya. This study explores corruption in Kenya's HIV response system and the implications for health outcomes from the perspective of people living with HIV (PLHIV). Although they might not be directly responsible for health care fund management, PLHIV and their advocacy efforts have been central to the development of HIV system response and they have a vested interest in ensuring proper governance. This phenomenological study was conducted in 2012 in Kiambu County in Kenya. The study was designed to capture the experiences of a select group of individuals living with HIV and AIDS and subsequent effects on intergenerational wealth transmission. Four focus groups were conducted with self-convened HIV/AIDS peer support groups. Findings related to corruption emerged unexpectedly, albeit consistently, across all four focus groups. To validate core themes within the data, including corruption, two coders independently reviewed and coded the data. Participants described incidences of resource misallocation, theft, and denial of services across three thematic levels namely at the interpersonal, provider, and institutional levels. Participants described the negative influence of corruption on their health and financial well-being, and propose: (1) strengthening legal protections for assets belonging to PLHIV, (2) direct representation of PLHIV within service agencies, (3) and addressing information asymmetries to inject transparency into the response system. Our findings add to the growing literature that identifies advocacy among individuals and families impacted by HIV and AIDS to be a useful tool in drawing attention to harmful practices in the HIV response infrastructure; consistent with this movement, communities in Kenya demand greater control over programmatic interventions both at the national and local levels.

  18. Prediction of exposed domains of envelope glycoprotein in Indian HIV-1 isolates and experimental confirmation of their immunogenicity in humans

    Directory of Open Access Journals (Sweden)

    Mohabatkar H.

    2004-01-01

    Full Text Available We describe the impact of subtype differences on the seroreactivity of linear antigenic epitopes in envelope glycoprotein of HIV-1 isolates from different geographical locations. By computer analysis, we predicted potential antigenic sites of envelope glycoprotein (gp120 and gp4l of this virus. For this purpose, after fetching sequences of proteins of interest from data banks, values of hydrophilicity, flexibility, accessibility, inverted hydrophobicity, and secondary structure were considered. We identified several potential antigenic epitopes in a B subtype strain of envelope glycoprotein of HIV-1 (IIIB. Solid- phase peptide synthesis methods of Merrifield and Fmoc chemistry were used for synthesizing peptides. These synthetic peptides corresponded mainly to the C2, V3 and CD4 binding sites of gp120 and some parts of the ectodomain of gp41. The reactivity of these peptides was tested by ELISA against different HIV-1-positive sera from different locations in India. For two of these predicted epitopes, the corresponding Indian consensus sequences (LAIERYLKQQLLGWG and DIIGDIRQAHCNISEDKWNET (subtype C were also synthesized and their reactivity was tested by ELISA. These peptides also distinguished HIV-1-positive sera of Indians with C subtype infections from sera from HIV-negative subjects.

  19. Prediction of mutational tolerance in HIV-1 protease and reverse transcriptase using flexible backbone protein design.

    Directory of Open Access Journals (Sweden)

    Elisabeth Humphris-Narayanan

    Full Text Available Predicting which mutations proteins tolerate while maintaining their structure and function has important applications for modeling fundamental properties of proteins and their evolution; it also drives progress in protein design. Here we develop a computational model to predict the tolerated sequence space of HIV-1 protease reachable by single mutations. We assess the model by comparison to the observed variability in more than 50,000 HIV-1 protease sequences, one of the most comprehensive datasets on tolerated sequence space. We then extend the model to a second protein, reverse transcriptase. The model integrates multiple structural and functional constraints acting on a protein and uses ensembles of protein conformations. We find the model correctly captures a considerable fraction of protease and reverse-transcriptase mutational tolerance and shows comparable accuracy using either experimentally determined or computationally generated structural ensembles. Predictions of tolerated sequence space afforded by the model provide insights into stability-function tradeoffs in the emergence of resistance mutations and into strengths and limitations of the computational model.

  20. Development and Validation of an HIV Risk Exposure and Indicator Conditions Questionnaire to Support Targeted HIV Screening.

    Science.gov (United States)

    Elías, María Jesús Pérez; Gómez-Ayerbe, Cristina; Elías, Pilar Pérez; Muriel, Alfonso; de Santiago, Alberto Diaz; Martinez-Colubi, María; Moreno, Ana; Santos, Cristina; Polo, Lidia; Barea, Rafa; Robledillo, Gema; Uranga, Almudena; Espín, Agustina Cano; Quereda, Carmen; Dronda, Fernando; Casado, Jose Luis; Moreno, Santiago

    2016-02-01

    The aim of our study was to develop a Spanish-structured HIV risk of exposure and indicator conditions (RE&IC) questionnaire. People attending to an emergency room or to a primary clinical care center were offered to participate in a prospective, 1 arm, open label study, in which all enrolled patients filled out our developed questionnaire and were HIV tested. Questionnaire accuracy, feasibility, and reliability were evaluated.Valid paired 5329 HIV RE&IC questionnaire and rapid HIV tests were performed, 69.3% in the primary clinical care center, 49.6% women, median age 37 years old, 74.9% Spaniards, 20.1% Latin-Americans. Confirmed hidden HIV infection was detected in 4.1%, while HIV RE&IC questionnaire was positive in 51.2%. HIV RE&IC questionnaire sensitivity was 100% to predict HIV infection, with a 100% negative predictive value. When considered separately, RE or IC items sensitivity decreases to 86.4% or 91%, and similarly their negative predictive value to 99.9% for both of them. The majority of people studied, 90.8% self-completed HIV RE&IC questionnaire. Median time to complete was 3 minutes. Overall HIV RE&IC questionnaire test-retest Kappa agreement was 0.82 (almost perfect), likewise for IC items 0.89, while for RE items was lower 0.78 (substantial).A feasible and reliable Spanish HIV RE&IC self questionnaire accurately discriminated all non-HIV-infected people without missing any HIV diagnoses, in a low prevalence HIV infection area. The best accuracy and reliability were obtained when combining HIV RE&IC items.

  1. Immunization of neonatal mice with LAMP/p55 HIV gag DNA elicits robust immune responses that last to adulthood

    International Nuclear Information System (INIS)

    Ordonhez Rigato, Paula; Maciel, Milton; Goldoni, Adriana Leticia; Piubelli, Orlando; Alves de Brito, Cyro; Fusaro, Ana Elisa; Eurico de Alencar, Liciana Xavier; August, Thomas; Torres Azevedo Marques, Ernesto; Silva Duarte, Alberto Jose da; Sato, Maria Notomi

    2010-01-01

    Successful T cell priming in early postnatal life that can generate effective long-lasting responses until adulthood is critical in HIV vaccination strategies because it prevents early sexual initiation and breastfeeding transmission of HIV. A chimeric DNA vaccine encoding p55 HIV gag associated with lysosome-associated membrane protein 1 (LAMP-1; which drives the antigen to the MIIC compartment), has been used to enhance cellular and humoral antigen-specific responses in adult mice and macaques. Herein, we investigated LAMP-1/gag vaccine immunogenicity in the neonatal period in mice and its ability to generate long-lasting effects. Neonatal vaccination with chimeric LAMP/gag generated stronger Gag-specific immune responses, as measured by the breadth of the Gag peptide-specific IFN-γ, proliferative responsiveness, cytokine production and antibody production, all of which revealed activation of CD4+ T cells as well as the generation of a more robust CTL response compared to gag vaccine alone. To induce long-lived T and B cell memory responses, it was necessary to immunize neonates with the chimeric LAMP/gag DNA vaccine. The LAMP/gag DNA vaccine strategy could be particularly useful for generating an anti-HIV immune response in the early postnatal period capable of inducing long-term immunological memory.

  2. Response of religious groups to HIV/AIDS as a sexually transmitted infection in Trinidad

    Directory of Open Access Journals (Sweden)

    Genrich Gillian L

    2005-11-01

    challenged to promote a clear and consistent response to the HIV/AIDS epidemic; a response that may reflect personal experiences and respect religious doctrine in the context of sex and sexuality. The study suggests that (1 religious leaders could improve their role in the fight against HIV/AIDS with education and sensitization-specifically aimed at dismantling the myths about HIV transmission, and the stereotyping of susceptible sub-populations, and (2 a consultative dialogue between PWHAs and religious leaders is pivotal to a successful faith-based HIV intervention in Trinidad.

  3. Focusing the HIV response through estimating the major modes of HIV transmission: a multi-country analysis

    Science.gov (United States)

    Gouws, Eleanor; Cuchi, Paloma

    2012-01-01

    Objective An increasing number of countries have been estimating the distribution of new adult HIV infections by modes of transmission (MOT) to help prioritise prevention efforts. We compare results from studies conducted between 2008 and 2012 and discuss their use for planning and responding to the HIV epidemic. Methods The UNAIDS recommended MOT model helps countries to estimate the proportion of new HIV infections that occur through key transmission modes including sex work, injecting drug use (IDU), men having sex with men (MSM), multiple sexual partnerships, stable relationships and medical interventions. The model typically forms part of a country-led process that includes a comprehensive review of epidemiological data. Recent revisions to the model are described. Results Modelling results from 25 countries show large variation between and within regions. In sub-Saharan Africa, new infections occur largely in the general heterosexual population because of multiple partnerships or in stable discordant relationships, while sex work contributes significantly to new infections in West Africa. IDU and sex work are the main contributors to new infections in the Middle East and North Africa, with MSM the main contributor in Latin America. Patterns vary substantially between countries in Eastern Europe and Asia in terms of the relative contribution of sex work, MSM, IDU and spousal transmission. Conclusions The MOT modelling results, comprehensive review and critical assessment of data in a country can contribute to a more strategically focused HIV response. To strengthen this type of research, improved epidemiological and behavioural data by risk population are needed. PMID:23172348

  4. Prevalence and Correlates of Non-Disclosure of HIV Serostatus to Sex partners among HIV-Infected Female Sex Workers and HIV-infected Male Clients of Female Sex Workers in India

    Science.gov (United States)

    Raj, Anita; Mahapatra, Bidhubhusan; Cheng, Debbie M.; Coleman, Sharon; Bridden, Carly; Battala, Madhusudana; Silverman, Jay G.; Pardeshi, Manoj H.; Samet, Jeffrey H.

    2013-01-01

    This study examines non-disclosure of HIV serostatus to sex partners among HIV-infected adults involved with transactional sex in Mumbai, India. Surveys were conducted with HIV-infected female sex workers (n = 211) and infected male clients (n = 205) regarding HIV knowledge, awareness of sex partners’ HIV serostatus, alcohol use, transactional sex involvement post-HIV diagnosis and non-disclosure of HIV serostatus. Gender-stratified multiple logistic regression models were used for analysis. Non-disclosure of one’s serostatus to all sex partners was reported by almost three-fifths of females and two-fifths of males. Predictors of non-disclosure included lack of correct knowledge about HIV and no knowledge of sex partners’ HIV serostatus. Among females, recent alcohol consumption also predicted non-disclosure. Among males, 10 + paid sexual partners in the year following HIV diagnosis predicted non-disclosure. Secondary HIV prevention efforts in India require greater focus on HIV disclosure communication and integrated alcohol and sexual risk reduction. PMID:22810892

  5. Inclusion of disability within national strategic responses to HIV and AIDS in Eastern and Southern Africa.

    Science.gov (United States)

    Hanass-Hancock, Jill; Strode, Ann; Grant, Catherine

    2011-01-01

    National strategic plans (NSPs) provide a framework for a comprehensive response to human immunodeficiency virus (HIV) including strategies such as prevention, treatment, care and support for all affected. Research indicates limited recognition of the interrelationship between disability and HIV in the Eastern and Southern Africa (ESA). This paper analyses the extent to which NSPs in ESA address disability, and identify good practice. Using a tool based on relevant rights in the UN Convention on the Rights of Persons with Disabilities and the UNAIDS International Guidelines on HIV and Human Rights, a review of 18 NSPs in ESA was conducted to determine the extent to which they included disability. Although many NSPs fail to integrate disability issues, there are examples of good practice from which much can be learned, particularly with respect to disability and HIV-prevention efforts. There is limited provision for treatment, care and support for disability in the context of HIV and AIDS. Many NSPs in ESA are due for review, providing ample opportunities for the development of disability-inclusive responses. Future NSPs need to integrate the needs of people with disabilities within structures, programmes and monitoring and evaluation, and make provision for increased rehabilitation needs caused by HIV. A rights-based approach and specific financial allocation of resources are crucial for this process.

  6. HIV-1 Adaptation to Antigen Processing Results in Population-Level Immune Evasion and Affects Subtype Diversification

    DEFF Research Database (Denmark)

    Tenzer, Stefan; Crawford, Hayley; Pymm, Phillip

    2014-01-01

    these regions encode epitopes presented by ~30 more common HLA variants. By combining epitope processing and computational analyses of the two HIV subtypes responsible for ~60% of worldwide infections, we identified a hitherto unrecognized adaptation to the antigen-processing machinery through substitutions...... of intrapatient adaptations, is predictable, facilitates viral subtype diversification, and increases global HIV diversity. Because low epitope abundance is associated with infrequent and weak T cell responses, this most likely results in both population-level immune evasion and inadequate responses in most...

  7. Addressing gender inequality and intimate partner violence as critical barriers to an effective HIV response in sub-Saharan Africa.

    Science.gov (United States)

    Watts, Charlotte; Seeley, Janet

    2014-01-01

    In Africa, women and girls represent 57% of people living with HIV, with gender inequality and violence being an important structural determinant of their vulnerability. This commentary draws out lessons for a more effective combination response to the HIV epidemic from three papers recently published in JIAS. Hatcher and colleagues present qualitative data from women attending ante-natal clinics in Johannesburg, describing how HIV diagnosis during pregnancy and subsequent partner disclosure are common triggers for violence within relationships. The authors describe the challenges women face in adhering to medication or using services. Kyegombe and colleagues present a secondary analysis of a randomized controlled trial in Uganda of SASA! - a community violence prevention programme. Along with promising community impacts on physical partner violence, significantly lower levels of sexual concurrency, condom use and HIV testing were reported by men in intervention communities. Remme and her colleagues present a systematic review of evidence on the costs and cost-effectiveness of gender-responsive HIV interventions. The review identified an ever-growing evidence base, but a paucity of accompanying economic analyses, making it difficult to assess the costs or value for money of gender-focused programmes. There is a need to continue to accumulate evidence on the effectiveness and costs of different approaches to addressing gender inequality and violence as part of a combination HIV response. A clearer HIV-specific and broader synergistic vision of financing and programming needs to be developed, to ensure that the potential synergies between HIV-specific and broader gender-focused development investments can be used to best effect to address vulnerability of women and girls to both violence and HIV.

  8. Computational models as predictors of HIV treatment outcomes for ...

    African Journals Online (AJOL)

    Background: Selecting the optimal combination of HIV drugs for an individual in resourcelimited settings is challenging because of the limited availability of drugs and genotyping. Objective: The evaluation as a potential treatment support tool of computational models that predict response to therapy without a genotype, ...

  9. Humans with chimpanzee-like major histocompatibility complex-specificities control HIV-1 infection

    DEFF Research Database (Denmark)

    Hoof, Ilka; Kesmir, Can; Lund, Ole

    2008-01-01

    and the progression rate to AIDS. Chimpanzees control HIV-1 viral replication and develop a chronic infection without progressing to AIDS. A similar course of disease is observed in human long-term non-progressors. Objective: To investigate if long-term non-progressors and chimpanzees have functional similarities...... in their MHC class I repertoire. Methods: We compared the specificity of groups of human MHC molecules associated with different levels of viremia in HIV-1 infected individuals with those of chimpanzee. Results and conclusion: We demonstrate that human MHC with control of HIV-1 viral load share binding motifs...... with chimpanzee MHC. Moreover, we find that chimpanzee and human MHC associated with low viral load are predicted to elicit broader Gag-specific immune responses than human MHC associated with high viral load, thus supporting earlier findings that Gag-specific immune responses are essential for HIV-1 control....

  10. Clinical, immunological and virological response to different antiretroviral regimens in a cohort of HIV-2-infected patients

    NARCIS (Netherlands)

    van der Ende, Marchina E.; Prins, Jan M.; Brinkman, Kees; Keuter, Monique; Veenstra, Jan; Danner, Sven A.; Niesters, Hubert G. M.; Osterhaus, Albert D. M. E.; Schutten, Martin

    2003-01-01

    Objective: To assess the clinical, immunological and virological response and the emergence of resistance towards antiretroviral therapy (ART) in a cohort of HIV-2-infected patients. Design: Observational study. Patients: HIV-2-infected patients residing in the Netherlands. Results: From 1995 to

  11. HIVsirDB: a database of HIV inhibiting siRNAs.

    Directory of Open Access Journals (Sweden)

    Atul Tyagi

    Full Text Available Human immunodeficiency virus (HIV is responsible for millions of deaths every year. The current treatment involves the use of multiple antiretroviral agents that may harm patients due to their toxic nature. RNA interference (RNAi is a potent candidate for the future treatment of HIV, uses short interfering RNA (siRNA/shRNA for silencing HIV genes. In this study, attempts have been made to create a database HIVsirDB of siRNAs responsible for silencing HIV genes.HIVsirDB is a manually curated database of HIV inhibiting siRNAs that provides comprehensive information about each siRNA or shRNA. Information was collected and compiled from literature and public resources. This database contains around 750 siRNAs that includes 75 partially complementary siRNAs differing by one or more bases with the target sites and over 100 escape mutant sequences. HIVsirDB structure contains sixteen fields including siRNA sequence, HIV strain, targeted genome region, efficacy and conservation of target sequences. In order to facilitate user, many tools have been integrated in this database that includes; i siRNAmap for mapping siRNAs on target sequence, ii HIVsirblast for BLAST search against database, iii siRNAalign for aligning siRNAs.HIVsirDB is a freely accessible database of siRNAs which can silence or degrade HIV genes. It covers 26 types of HIV strains and 28 cell types. This database will be very useful for developing models for predicting efficacy of HIV inhibiting siRNAs. In summary this is a useful resource for researchers working in the field of siRNA based HIV therapy. HIVsirDB database is accessible at http://crdd.osdd.net/raghava/hivsir/.

  12. HIV-Specific B Cell Frequency Correlates with Neutralization Breadth in Patients Naturally Controlling HIV-Infection

    Directory of Open Access Journals (Sweden)

    Angeline Rouers

    2017-07-01

    Full Text Available HIV-specific broadly neutralizing antibodies (bnAbs have been isolated from patients with high viremia but also from HIV controllers that repress HIV-1 replication. In these elite controllers (ECs, multiple parameters contribute to viral suppression, including genetic factors and immune responses. Defining the immune correlates associated with the generation of bnAbs may help in designing efficient immunotherapies. In this study, in ECs either positive or negative for the HLA-B*57 protective allele, in treated HIV-infected and HIV-negative individuals, we characterized memory B cell compartments and HIV-specific memory B cells responses using flow cytometry and ELISPOT. ECs preserved their memory B cell compartments and in contrast to treated patients, maintained detectable HIV-specific memory B cell responses. All ECs presented IgG1+ HIV-specific memory B cells but some individuals also preserved IgG2+ or IgG3+ responses. Importantly, we also analyzed the capacity of sera from ECs to neutralize a panel of HIV strains including transmitted/founder virus. 29% and 21% of HLA-B*57+ and HLA-B*57− ECs, respectively, neutralized at least 40% of the viral strains tested. Remarkably, in HLA-B*57+ ECs the frequency of HIV-Env-specific memory B cells correlated positively with the neutralization breadth suggesting that preservation of HIV-specific memory B cells might contribute to the neutralizing responses in these patients.

  13. Global HIV/AIDS Epidemic

    Science.gov (United States)

    ... Policy The Global HIV/AIDS Epidemic The Global HIV/AIDS Epidemic Published: Nov 29, 2017 Facebook Twitter ... 2001-FY 2018 Request The Global Response to HIV/AIDS International efforts to combat HIV began in ...

  14. Monitoring linked epidemics: the case of tuberculosis and HIV.

    Directory of Open Access Journals (Sweden)

    María S Sánchez

    Full Text Available BACKGROUND: The tight epidemiological coupling between HIV and its associated opportunistic infections leads to challenges and opportunities for disease surveillance. METHODOLOGY/PRINCIPAL FINDINGS: We review efforts of WHO and collaborating agencies to track and fight the TB/HIV co-epidemic, and discuss modeling--via mathematical, statistical, and computational approaches--as a means to identify disease indicators designed to integrate data from linked diseases in order to characterize how co-epidemics change in time and space. We present R(TB/HIV, an index comparing changes in TB incidence relative to HIV prevalence, and use it to identify those sub-Saharan African countries with outlier TB/HIV dynamics. R(TB/HIV can also be used to predict epidemiological trends, investigate the coherency of reported trends, and cross-check the anticipated impact of public health interventions. Identifying the cause(s responsible for anomalous R(TB/HIV values can reveal information crucial to the management of public health. CONCLUSIONS/SIGNIFICANCE: We frame our suggestions for integrating and analyzing co-epidemic data within the context of global disease monitoring. Used routinely, joint disease indicators such as R(TB/HIV could greatly enhance the monitoring and evaluation of public health programs.

  15. HIV-specific Fc effector function early in infection predicts the development of broadly neutralizing antibodies.

    Directory of Open Access Journals (Sweden)

    Simone I Richardson

    2018-04-01

    Full Text Available While the induction of broadly neutralizing antibodies (bNAbs is a major goal of HIV vaccination strategies, there is mounting evidence to suggest that antibodies with Fc effector function also contribute to protection against HIV infection. Here we investigated Fc effector functionality of HIV-specific IgG plasma antibodies over 3 years of infection in 23 individuals, 13 of whom developed bNAbs. Antibody-dependent cellular phagocytosis (ADCP, complement deposition (ADCD, cellular cytotoxicity (ADCC and cellular trogocytosis (ADCT were detected in almost all individuals with levels of activity increasing over time. At 6 months post-infection, individuals with bNAbs had significantly higher levels of ADCD and ADCT that correlated with antibody binding to C1q and FcγRIIa respectively. In addition, antibodies from individuals with bNAbs showed more IgG subclass diversity to multiple HIV antigens which also correlated with Fc polyfunctionality. Germinal center activity represented by CXCL13 levels and expression of activation-induced cytidine deaminase (AID was found to be associated with neutralization breadth, Fc polyfunctionality and IgG subclass diversity. Overall, multivariate analysis by random forest classification was able to group bNAb individuals with 85% sensitivity and 80% specificity based on the properties of their antibody Fc early in HIV infection. Thus, the Fc effector function profile predicted the development of neutralization breadth in this cohort, suggesting that intrinsic immune factors within the germinal center provide a mechanistic link between the Fc and Fab of HIV-specific antibodies.

  16. Use of four next-generation sequencing platforms to determine HIV-1 coreceptor tropism.

    Science.gov (United States)

    Archer, John; Weber, Jan; Henry, Kenneth; Winner, Dane; Gibson, Richard; Lee, Lawrence; Paxinos, Ellen; Arts, Eric J; Robertson, David L; Mimms, Larry; Quiñones-Mateu, Miguel E

    2012-01-01

    HIV-1 coreceptor tropism assays are required to rule out the presence of CXCR4-tropic (non-R5) viruses prior treatment with CCR5 antagonists. Phenotypic (e.g., Trofile™, Monogram Biosciences) and genotypic (e.g., population sequencing linked to bioinformatic algorithms) assays are the most widely used. Although several next-generation sequencing (NGS) platforms are available, to date all published deep sequencing HIV-1 tropism studies have used the 454™ Life Sciences/Roche platform. In this study, HIV-1 co-receptor usage was predicted for twelve patients scheduled to start a maraviroc-based antiretroviral regimen. The V3 region of the HIV-1 env gene was sequenced using four NGS platforms: 454™, PacBio® RS (Pacific Biosciences), Illumina®, and Ion Torrent™ (Life Technologies). Cross-platform variation was evaluated, including number of reads, read length and error rates. HIV-1 tropism was inferred using Geno2Pheno, Web PSSM, and the 11/24/25 rule and compared with Trofile™ and virologic response to antiretroviral therapy. Error rates related to insertions/deletions (indels) and nucleotide substitutions introduced by the four NGS platforms were low compared to the actual HIV-1 sequence variation. Each platform detected all major virus variants within the HIV-1 population with similar frequencies. Identification of non-R5 viruses was comparable among the four platforms, with minor differences attributable to the algorithms used to infer HIV-1 tropism. All NGS platforms showed similar concordance with virologic response to the maraviroc-based regimen (75% to 80% range depending on the algorithm used), compared to Trofile (80%) and population sequencing (70%). In conclusion, all four NGS platforms were able to detect minority non-R5 variants at comparable levels suggesting that any NGS-based method can be used to predict HIV-1 coreceptor usage.

  17. Use of four next-generation sequencing platforms to determine HIV-1 coreceptor tropism.

    Directory of Open Access Journals (Sweden)

    John Archer

    Full Text Available HIV-1 coreceptor tropism assays are required to rule out the presence of CXCR4-tropic (non-R5 viruses prior treatment with CCR5 antagonists. Phenotypic (e.g., Trofile™, Monogram Biosciences and genotypic (e.g., population sequencing linked to bioinformatic algorithms assays are the most widely used. Although several next-generation sequencing (NGS platforms are available, to date all published deep sequencing HIV-1 tropism studies have used the 454™ Life Sciences/Roche platform. In this study, HIV-1 co-receptor usage was predicted for twelve patients scheduled to start a maraviroc-based antiretroviral regimen. The V3 region of the HIV-1 env gene was sequenced using four NGS platforms: 454™, PacBio® RS (Pacific Biosciences, Illumina®, and Ion Torrent™ (Life Technologies. Cross-platform variation was evaluated, including number of reads, read length and error rates. HIV-1 tropism was inferred using Geno2Pheno, Web PSSM, and the 11/24/25 rule and compared with Trofile™ and virologic response to antiretroviral therapy. Error rates related to insertions/deletions (indels and nucleotide substitutions introduced by the four NGS platforms were low compared to the actual HIV-1 sequence variation. Each platform detected all major virus variants within the HIV-1 population with similar frequencies. Identification of non-R5 viruses was comparable among the four platforms, with minor differences attributable to the algorithms used to infer HIV-1 tropism. All NGS platforms showed similar concordance with virologic response to the maraviroc-based regimen (75% to 80% range depending on the algorithm used, compared to Trofile (80% and population sequencing (70%. In conclusion, all four NGS platforms were able to detect minority non-R5 variants at comparable levels suggesting that any NGS-based method can be used to predict HIV-1 coreceptor usage.

  18. HIV prevention fatigue and HIV treatment optimism among young men who have sex with men

    Science.gov (United States)

    Macapagal, Kathryn; Birkett, Michelle; Janulis, Patrick; Garofalo, Robert; Mustanski, Brian

    2017-01-01

    HIV prevention fatigue (the sense that prevention messages are tiresome) and being overly optimistic about HIV treatments are hypothesized to increase HIV risk behavior. Little research has examined these constructs and their correlates among young men who have sex with men (YMSM), who are at high risk for HIV. YMSM (N = 352; M age = 20; 50% Black) completed measures of prevention fatigue, treatment optimism, HIV risk behaviors, and HIV-related knowledge and attitudes during a longitudinal study. Overall, YMSM reported low levels of HIV prevention fatigue and treatment optimism. Path analysis (n = 307) indicated that greater prevention fatigue and treatment optimism predicted higher rates of condomless sex, but condomless sex did not predict later increases in prevention fatigue or treatment optimism. Results are inconsistent with the hypothesis of high prevention fatigue and treatment optimism among YMSM and point to potential causal relationships among these variables and condomless sex. PMID:28825861

  19. Lymphocyte transformation response to pokeweed mitogen as a predictive marker for development of AIDS and AIDS related symptoms in homosexual men with HIV antibodies

    DEFF Research Database (Denmark)

    Hofmann, B; Lindhardt, B O; Gerstoft, J

    1987-01-01

    To identify factors that may predict the development of the acquired immune deficiency syndrome (AIDS) or AIDS related symptoms various immunological measurements were studied in a group of homosexual men attending screening clinics for AIDS in Copenhagen. Fifty seven men whose ratio of T helper...... lymphocytes to T suppressor lymphocytes (CD4:CD8 ratio) was less than 1.0 before the study began were included. Forty two were positive for antibody to the human immunodeficiency virus (HIV), of whom 38 were reinvestigated after a median observation period of 10 months. Among the seropositive men...

  20. Celastrol ameliorates HIV-1 Tat-induced inflammatory responses via NF-kappaB and AP-1 inhibition and heme oxygenase-1 induction in astrocytes

    International Nuclear Information System (INIS)

    Youn, Gi Soo; Kwon, Dong-Joo; Ju, Sung Mi; Rhim, Hyangshuk; Bae, Yong Soo; Choi, Soo Young; Park, Jinseu

    2014-01-01

    HIV-1 Tat causes extensive neuroinflammation that may progress to AIDS-related encephalitis and dementia. Celastrol possesses various biological activities such as anti-oxidant, anti-tumor, and anti-inflammatory activities. In this study, we investigated the modulatory effects of celastrol on HIV-1 Tat-induced inflammatory responses and the molecular mechanisms underlying its action in astrocytes. Pre-treatment of CRT-MG human astroglioma cells with celastrol significantly inhibited HIV-1 Tat-induced expression of ICAM-1/VCAM-1 and subsequent monocyte adhesiveness in CRT-MG cells. In addition, celastrol suppressed HIV-1 Tat-induced expression of pro-inflammatory chemokines, such as CXCL10, IL-8, and MCP-1. Celastrol decreased HIV-1 Tat-induced activation of JNK MAPK, AP-1, and NF-κB. Furthermore, celastrol induced mRNA and protein expression of HO-1 as well as Nrf2 activation. Blockage of HO-1 expression using siRNA reversed the inhibitory effect of celastrol on HIV-1 Tat-induced inflammatory responses. These results suggest that celastrol has regulatory effects on HIV-1 Tat-induced inflammatory responses by blocking the JNK MAPK-AP-1/NF-κB signaling pathways and inducing HO-1 expression in astrocytes. - Highlights: • Celastrol suppressed HIV-1 Tat-induced expression of pro-inflammatory genes. • Celastrol inhibited HIV-1 Tat -induced activation of JNK MAPK. • Celastrol inhibited HIV-1 Tat-induced activation of both NF-κB and AP-1. • Celastrol inhibited HIV-1 Tat-induced inflammatory responses via HO-1 induction

  1. Celastrol ameliorates HIV-1 Tat-induced inflammatory responses via NF-kappaB and AP-1 inhibition and heme oxygenase-1 induction in astrocytes

    Energy Technology Data Exchange (ETDEWEB)

    Youn, Gi Soo; Kwon, Dong-Joo; Ju, Sung Mi [Department of Biomedical Science and Research Institute for Bioscience and Biotechnology, Hallym University, Chunchon 200-702 (Korea, Republic of); Rhim, Hyangshuk [Department of Biomedical Sciences, Department of Medical Life Sciences, College of Medicine, the Catholic University of Korea, Seoul 137-701 (Korea, Republic of); Bae, Yong Soo [Department of Biological Science, College of Natural Sciences, Sungkyunkwan University, Suwon 440-746 (Korea, Republic of); Choi, Soo Young [Department of Biomedical Science and Research Institute for Bioscience and Biotechnology, Hallym University, Chunchon 200-702 (Korea, Republic of); Park, Jinseu, E-mail: jinpark@hallym.ac.kr [Department of Biomedical Science and Research Institute for Bioscience and Biotechnology, Hallym University, Chunchon 200-702 (Korea, Republic of)

    2014-10-01

    HIV-1 Tat causes extensive neuroinflammation that may progress to AIDS-related encephalitis and dementia. Celastrol possesses various biological activities such as anti-oxidant, anti-tumor, and anti-inflammatory activities. In this study, we investigated the modulatory effects of celastrol on HIV-1 Tat-induced inflammatory responses and the molecular mechanisms underlying its action in astrocytes. Pre-treatment of CRT-MG human astroglioma cells with celastrol significantly inhibited HIV-1 Tat-induced expression of ICAM-1/VCAM-1 and subsequent monocyte adhesiveness in CRT-MG cells. In addition, celastrol suppressed HIV-1 Tat-induced expression of pro-inflammatory chemokines, such as CXCL10, IL-8, and MCP-1. Celastrol decreased HIV-1 Tat-induced activation of JNK MAPK, AP-1, and NF-κB. Furthermore, celastrol induced mRNA and protein expression of HO-1 as well as Nrf2 activation. Blockage of HO-1 expression using siRNA reversed the inhibitory effect of celastrol on HIV-1 Tat-induced inflammatory responses. These results suggest that celastrol has regulatory effects on HIV-1 Tat-induced inflammatory responses by blocking the JNK MAPK-AP-1/NF-κB signaling pathways and inducing HO-1 expression in astrocytes. - Highlights: • Celastrol suppressed HIV-1 Tat-induced expression of pro-inflammatory genes. • Celastrol inhibited HIV-1 Tat -induced activation of JNK MAPK. • Celastrol inhibited HIV-1 Tat-induced activation of both NF-κB and AP-1. • Celastrol inhibited HIV-1 Tat-induced inflammatory responses via HO-1 induction.

  2. Weak anti-HIV CD8+ T-cell effector activity in HIV primary infection

    Science.gov (United States)

    Dalod, Marc; Dupuis, Marion; Deschemin, Jean-Christophe; Goujard, Cécile; Deveau, Christiane; Meyer, Laurence; Ngo, Nicole; Rouzioux, Christine; Guillet, Jean-Gérard; Delfraissy, Jean-François; Sinet, Martine; Venet, Alain

    1999-01-01

    HIV-specific CD8+ T cells play a major role in the control of virus during HIV primary infection (PI) but do not completely prevent viral replication. We used IFN-γ enzyme-linked immunospot assay and intracellular staining to characterize the ex vivo CD8+ T-cell responses to a large variety of HIV epitopic peptides in 24 subjects with early HIV PI. We observed HIV-specific responses in 71% of subjects. Gag and Nef peptides were more frequently recognized than Env and Pol peptides. The number of peptides recognized was low (median 2, range 0–6). In contrast, a much broader response was observed in 30 asymptomatic subjects with chronic infection: all were responders with a median of 5 peptides recognized (range 1–13). The frequency of HIV-specific CD8+ T cells among PBMC for a given peptide was of the same order of magnitude in both groups. The proportion of HIV-specific CD8+CD28– terminally differentiated T cells was much lower in PI than at the chronic stage of infection. The weakness of the immune response during HIV PI could partially account for the failure to control HIV. These findings have potential importance for defining immunotherapeutic strategies and establishing the goals for effective vaccination. J. Clin. Invest. 104:1431–1439 (1999). PMID:10562305

  3. Public-private partnerships in the response to HIV: experience from the resource industry in Papua New Guinea.

    Science.gov (United States)

    Miles, K; Conlon, M; Stinshoff, J; Hutton, R

    2014-01-01

    Although Papua New Guinea (PNG) has made some progress in social development over the past 30 years, the country's Human Development Index has slowed in recent years, placing it below the regional average. In 2012, the estimated HIV prevalence for adults aged 15-49 years was 0.5% and an estimated 25,000 people were living with HIV. Although reduced from previous estimates, the country's HIV prevalence remains the highest in the South Pacific region. While the faith-based and non-governmental sectors have engaged in HIV interventions since the epidemic began, until recently the corporate sector has remained on the margins of the national response. In 2008, the country's largest oil and gas producer began partnering with national and provincial health authorities, development partners and global financing institutions to contribute to the national HIV strategy and implementation plan. This article provides an overview of public-private partnerships (PPPs) and their application to public health program management, and then describes the PPP that was developed in PNG. Innovative national and local PPPs have become a core component of healthcare strategy in many countries. PPPs have many forms and their use in low- and middle-income countries has progressively demonstrated increased service outputs and health outcomes beyond what the public sector alone could achieve. A PPP in PNG has resulted in an oil and gas producer engaging in the response to HIV, including managing the country's US$46 million HIV grant from the Global Fund to Fight AIDS, Tuberculosis and Malaria. Given the increasing expectations of the international community in relation to corporate responsibility and sustainability, the role of the corporate sector in countries like PNG is critical. Combining philanthropic investment with business strategy, expertise and organisational resource can contribute to enhancing health system structures and capacity.

  4. Correlates of HIV stigma in HIV-positive women.

    Science.gov (United States)

    Wagner, Anne C; Hart, Trevor A; Mohammed, Saira; Ivanova, Elena; Wong, Joanna; Loutfy, Mona R

    2010-06-01

    We examined the variables associated with HIV stigma in HIV-positive women currently living in Ontario, Canada. Based on previous literature, we predicted that variables of social marginalization (e.g., ethnicity, income, education), medical variables (e.g., higher CD4 count, lower viral load), and increased psychological distress would be associated with higher perceived HIV stigma among HIV-positive women. One hundred fifty-nine HIV-positive women between the ages of 18 and 52 in Ontario completed self-report measures of the aforementioned variables. Women were recruited through 28 AIDS service organizations, eight HIV clinics, and two community health centers. In multiple regression analyses, for women born in Canada, lower educational level and higher anxiety were associated with higher HIV stigma. For women born outside of Canada, having been judged by a physician in Canada for trying to become pregnant was associated with higher HIV stigma. For HIV-positive women born outside of Canada, negative judgment by a physician regarding intentions to become pregnant should be addressed to reduce perceived HIV stigma and vice versa. Health care providers should be trained in the provision of sensitive and effective health care for women living with HIV, especially when providing reproductive health care.

  5. Persistence of memory B-cell and T-cell responses to the quadrivalent HPV vaccine in HIV-infected children.

    Science.gov (United States)

    Weinberg, Adriana; Huang, Sharon; Moscicki, Anna-Barbara; Saah, Afred; Levin, Myron J

    2018-04-24

    To determine the magnitude and persistence of quadrivalent human papillomavirus (HPV)16 and HPV18 B-cell and T-cell memory after three or four doses of quadrivalent HPV vaccine (QHPV) in HIV-infected children. Seventy-four HIV-infected children immunized with four doses and 23 with three doses of QHPV had HPV16 and HPV18 IgG B-cell and IFNγ and IL2 T-cell ELISPOT performed at 2, 3.5 and 4-5 years after the last dose. HPV16 and HPV18 T-cell responses were similar in both treatment groups, with higher responses to HPV16 vs. HPV18. These HPV T-cell responses correlated with HIV disease characteristics at the study visits. Global T-cell function declined over time as measured by nonspecific mitogenic stimulation. B-cell memory was similar across treatment groups and HPV genotypes. There was a decline in HPV-specific B-cell memory over time that reached statistical significance for HPV16 in the four-dose group. B-cell and T-cell memory did not significantly differ after either three or four doses of QHPV in HIV-infected children. The clinical consequences of decreasing global T-cell function and HPV B-cell memory over time in HIV-infected children requires further investigation.

  6. Computational Study to Determine When to Initiate and Alternate Therapy in HIV Infection

    Directory of Open Access Journals (Sweden)

    Matthias Haering

    2014-01-01

    Full Text Available HIV is a widespread viral infection without cure. Drug treatment has transformed HIV disease into a treatable long-term infection. However, the appearance of mutations within the viral genome reduces the susceptibility of HIV to drugs. Therefore, a key goal is to extend the time until patients exhibit resistance to all existing drugs. Current HIV treatment guidelines seem poorly supported as practitioners have not achieved a consensus on the optimal time to initiate and to switch antiretroviral treatments. We contribute to this discussion with predictions derived from a mathematical model of HIV dynamics. Our results indicate that early therapy initiation (within 2 years postinfection is critical to delay AIDS progression. For patients who have not received any therapy during the first 3 years postinfection, switch in response to virological failure may outperform proactive switching strategies. In case that proactive switching is opted, the switching time between therapies should not be larger than 100 days. Further clinical trials are needed to either confirm or falsify these predictions.

  7. HIV epidemiology and responses among men who have sex with men and transgender individuals in China: a scoping review

    Directory of Open Access Journals (Sweden)

    Songyuan Tang

    2016-10-01

    Full Text Available Abstract Background Despite global efforts to control HIV among key populations, new infections among men who have sex with men (MSM and transgender (TG individuals are still increasing. The increasing HIV epidemic among MSM/TG in China indicates that more effective services are urgently needed. However, policymakers and program managers must have a clear understanding of MSM/TG sexual health in China to improve service delivery. To meet this need, we undertook a scoping review to summarize HIV epidemiology and responses among MSM and TG individuals in China. Methods We searched MEDLINE, EMBASE and the Cochrane Library for recent studies on MSM/TG HIV epidemiology and responses. We also included supplemental articles, grey literature, government reports, policy documents, and best practice guidelines. Results Overall, HIV prevalence among Chinese MSM was approximately 8 % in 2015 with a higher prevalence observed in Southwest China. TG are not captured in national HIV, STD, or other sexual health surveillance systems. There is limited data sharing between the public health authorities and community-based organizations (CBOs. Like other low and middle income countries, China is challenged by low rates of HIV testing, linkage, and retention. Several pilot interventions have been shown to be effective to increase HIV testing among MSM and TG individuals, but have not been widely scaled up. Data from two randomized controlled trials suggests that crowdsourcing contests can increase HIV testing, creating demand for services while engaging communities. Conclusion Improving HIV surveillance and expanding HIV interventions for Chinese MSM and TG individuals are essential. Further implementation research is needed to ensure high-quality HIV services for MSM and TG individuals in China.

  8. Predictive Utility of Brief AUDIT for HIV Antiretroviral Medication Nonadherence

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    Broyles, Lauren Matukaitis; Gordon, Adam J.; Sereika, Susan M.; Ryan, Christopher M.; Erlen, Judith A.

    2012-01-01

    Alcohol use negatively affects adherence to antiretroviral therapy (ART), thus HIV/AIDS providers need accurate, efficient assessments of alcohol use. Using existing data from an efficacy trial of two cognitive-behavioral ART adherence interventions, we sought to determine if results on two common alcohol screening tests (Alcohol Use Disorders Identification Test—Consumption (AUDIT-C) and its binge-related question (AUDIT-3)) predict ART nonadherence. Twenty seven percent of the sample (n=308) were positive on the AUDIT-C and 34% were positive on the AUDIT-3. In multivariate analyses, AUDIT-C positive status predicted ART nonadherence after controlling for race, age, conscientiousness, and self-efficacy (p=.036). While AUDIT-3 positive status was associated with ART nonadherence in unadjusted analyses, this relationship was not maintained in the final multivariate model. The AUDIT-C shows potential as an indirect screening tool for both at-risk drinking and ART nonadherence, underscoring the relationship between alcohol and chronic disease management. PMID:22014256

  9. Altered Memory T-Cell Responses to Bacillus Calmette-Guerin and Tetanus Toxoid Vaccination and Altered Cytokine Responses to Polyclonal Stimulation in HIV-Exposed Uninfected Kenyan Infants.

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    Garcia-Knight, Miguel A; Nduati, Eunice; Hassan, Amin S; Gambo, Faith; Odera, Dennis; Etyang, Timothy J; Hajj, Nassim J; Berkley, James Alexander; Urban, Britta C; Rowland-Jones, Sarah L

    2015-01-01

    Implementation of successful prevention of mother-to-child transmission of HIV strategies has resulted in an increased population of HIV-exposed uninfected (HEU) infants. HEU infants have higher rates of morbidity and mortality than HIV-unexposed (HU) infants. Numerous factors may contribute to poor health in HEU infants including immunological alterations. The present study assessed T-cell phenotype and function in HEU infants with a focus on memory Th1 responses to vaccination. We compared cross-sectionally selected parameters at 3 and 12 months of age in HIV-exposed (n = 42) and HU (n = 28) Kenyan infants. We measured ex vivo activated and bulk memory CD4 and CD8 T-cells and regulatory T-cells by flow cytometry. In addition, we measured the magnitude, quality and memory phenotype of antigen-specific T-cell responses to Bacillus Calmette-Guerin and Tetanus Toxoid vaccine antigens, and the magnitude and quality of the T cell response following polyclonal stimulation with staphylococcal enterotoxin B. Finally, the influence of maternal disease markers on the immunological parameters measured was assessed in HEU infants. Few perturbations were detected in ex vivo T-cell subsets, though amongst HEU infants maternal HIV viral load positively correlated with CD8 T cell immune activation at 12 months. Conversely, we observed age-dependent differences in the magnitude and polyfunctionality of IL-2 and TNF-α responses to vaccine antigens particularly in Th1 cells. These changes mirrored those seen following polyclonal stimulation, where at 3 months, cytokine responses were higher in HEU infants compared to HU infants, and at 12 months, HEU infant cytokine responses were consistently lower than those seen in HU infants. Finally, reduced effector memory Th1 responses to vaccine antigens were observed in HEU infants at 3 and 12 months and higher central memory Th1 responses to M. tuberculosis antigens were observed at 3 months only. Long-term monitoring of vaccine efficacy

  10. Altered Memory T-Cell Responses to Bacillus Calmette-Guerin and Tetanus Toxoid Vaccination and Altered Cytokine Responses to Polyclonal Stimulation in HIV-Exposed Uninfected Kenyan Infants.

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    Miguel A Garcia-Knight

    Full Text Available Implementation of successful prevention of mother-to-child transmission of HIV strategies has resulted in an increased population of HIV-exposed uninfected (HEU infants. HEU infants have higher rates of morbidity and mortality than HIV-unexposed (HU infants. Numerous factors may contribute to poor health in HEU infants including immunological alterations. The present study assessed T-cell phenotype and function in HEU infants with a focus on memory Th1 responses to vaccination. We compared cross-sectionally selected parameters at 3 and 12 months of age in HIV-exposed (n = 42 and HU (n = 28 Kenyan infants. We measured ex vivo activated and bulk memory CD4 and CD8 T-cells and regulatory T-cells by flow cytometry. In addition, we measured the magnitude, quality and memory phenotype of antigen-specific T-cell responses to Bacillus Calmette-Guerin and Tetanus Toxoid vaccine antigens, and the magnitude and quality of the T cell response following polyclonal stimulation with staphylococcal enterotoxin B. Finally, the influence of maternal disease markers on the immunological parameters measured was assessed in HEU infants. Few perturbations were detected in ex vivo T-cell subsets, though amongst HEU infants maternal HIV viral load positively correlated with CD8 T cell immune activation at 12 months. Conversely, we observed age-dependent differences in the magnitude and polyfunctionality of IL-2 and TNF-α responses to vaccine antigens particularly in Th1 cells. These changes mirrored those seen following polyclonal stimulation, where at 3 months, cytokine responses were higher in HEU infants compared to HU infants, and at 12 months, HEU infant cytokine responses were consistently lower than those seen in HU infants. Finally, reduced effector memory Th1 responses to vaccine antigens were observed in HEU infants at 3 and 12 months and higher central memory Th1 responses to M. tuberculosis antigens were observed at 3 months only. Long-term monitoring of

  11. HIV-1 with multiple CCR5/CXCR4 chimeric receptor use is predictive of immunological failure in infected children.

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    Mariangela Cavarelli

    Full Text Available BACKGROUND: HIV-1 R5 viruses are characterized by a large phenotypic variation, that is reflected by the mode of coreceptor use. The ability of R5 HIV-1 to infect target cells expressing chimeric receptors between CCR5 and CXCR4 (R5(broad viruses, was shown to correlate with disease stage in HIV-1 infected adults. Here, we ask the question whether phenotypic variation of R5 viruses could play a role also in mother-to-child transmission (MTCT of HIV-1 and pediatric disease progression. METHODOLOGY/PRINCIPAL FINDINGS: Viral isolates obtained from a total of 59 HIV-1 seropositive women (24 transmitting and 35 non transmitting and 28 infected newborn children, were used to infect U87.CD4 cells expressing wild type or six different CCR5/CXCR4 chimeric receptors. HIV-1 isolates obtained from newborn infants had predominantly R5(narrow phenotype (n = 20, but R5(broad and R5X4 viruses were also found in seven and one case, respectively. The presence of R5(broad and R5X4 phenotypes correlated significantly with a severe decline of the CD4+ T cells (CDC stage 3 or death within 2 years of age. Forty-three percent of the maternal R5 isolates displayed an R5(broad phenotype, however, the presence of the R5(broad virus was not predictive for MTCT of HIV-1. Of interest, while only 1 of 5 mothers with an R5X4 virus transmitted the dualtropic virus, 5 of 6 mothers carrying R5(broad viruses transmitted viruses with a similar broad chimeric coreceptor usage. Thus, the maternal R5(broad phenotype was largely preserved during transmission and could be predictive of the phenotype of the newborn's viral variant. CONCLUSIONS/SIGNIFICANCE: Our results show that R5(broad viruses are not hampered in transmission. When transmitted, immunological failure occurs earlier than in children infected with HIV-1 of R5(narrow phenotype. We believe that this finding is of utmost relevance for therapeutic interventions in pediatric HIV-1 infection.

  12. A recoding method to improve the humoral immune response to an HIV DNA vaccine.

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    Yaoxing Huang

    Full Text Available This manuscript describes a novel strategy to improve HIV DNA vaccine design. Employing a new information theory based bioinformatic algorithm, we identify a set of nucleotide motifs which are common in the coding region of HIV, but are under-represented in genes that are highly expressed in the human genome. We hypothesize that these motifs contribute to the poor protein expression of gag, pol, and env genes from the c-DNAs of HIV clinical isolates. Using this approach and beginning with a codon optimized consensus gag gene, we recode the nucleotide sequence so as to remove these motifs without modifying the amino acid sequence. Transfecting the recoded DNA sequence into a human kidney cell line results in doubling the gag protein expression level compared to the codon optimized version. We then turn both sequences into DNA vaccines and compare induced antibody response in a murine model. Our sequence, which has the motifs removed, induces a five-fold increase in gag antibody response compared to the codon optimized vaccine.

  13. Nonlinear observer output-feedback MPC treatment scheduling for HIV

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    Zurakowski Ryan

    2011-05-01

    Full Text Available Abstract Background Mathematical models of the immune response to the Human Immunodeficiency Virus demonstrate the potential for dynamic schedules of Highly Active Anti-Retroviral Therapy to enhance Cytotoxic Lymphocyte-mediated control of HIV infection. Methods In previous work we have developed a model predictive control (MPC based method for determining optimal treatment interruption schedules for this purpose. In this paper, we introduce a nonlinear observer for the HIV-immune response system and an integrated output-feedback MPC approach for implementing the treatment interruption scheduling algorithm using the easily available viral load measurements. We use Monte-Carlo approaches to test robustness of the algorithm. Results The nonlinear observer shows robust state tracking while preserving state positivity both for continuous and discrete measurements. The integrated output-feedback MPC algorithm stabilizes the desired steady-state. Monte-Carlo testing shows significant robustness to modeling error, with 90% success rates in stabilizing the desired steady-state with 15% variance from nominal on all model parameters. Conclusions The possibility of enhancing immune responsiveness to HIV through dynamic scheduling of treatment is exciting. Output-feedback Model Predictive Control is uniquely well-suited to solutions of these types of problems. The unique constraints of state positivity and very slow sampling are addressable by using a special-purpose nonlinear state estimator, as described in this paper. This shows the possibility of using output-feedback MPC-based algorithms for this purpose.

  14. Use of human papillomavirus DNA, E6/E7 mRNA, and p16 immunocytochemistry to detect and predict anal high-grade squamous intraepithelial lesions in HIV-positive and HIV-negative men who have sex with men.

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    Nittaya Phanuphak

    Full Text Available Men who have sex with men (MSM are at high risk of having anal cancer. Anal high-grade squamous intraepithelial lesion (HSIL is the precursor of anal cancer. We explored the use of different biomarkers associated with human papillomavirus (HPV infection and HPV-mediated cell transformation to detect and predict HSIL among HIV-positive and HIV-negative MSM.A total of 123 HIV-positive and 123 HIV-negative MSM were enrolled and followed for 12 months. High-resolution anoscopy (HRA with biopsies were performed at every visit along with anal sample collection for cytology, high-risk HPV DNA genotyping, HPV E6/E7 mRNA, and p16 immunocytochemistry. Performance characteristics and area under the receiver operator characteristics curve were calculated for these biomarkers at baseline, and Cox regression compared the usefulness of these biomarkers in predicting incident HSIL. High-risk HPV DNA, E6/E7 mRNA, and p16 immunocytochemistry each identified 43-46% of MSM whose baseline test positivity would trigger HRA referral. E6/E7 mRNA had the highest sensitivity (64.7% and correctly classified the highest number of prevalent HSIL cases. With the exception of p16 immunochemistry, most tests showed significant increases in sensitivity but decreases specificity versus anal cytology, while the overall number of correctly classified cases was not significantly different. Baseline or persistent type 16 and/or 18 HPV DNA was the only test significantly predicting incident histologic HSIL within 12 months in models adjusted for HIV status and low-grade squamous intraepithelial lesions at baseline.Countries with a high HIV prevalence among MSM and limited HRA resources may consider using biomarkers to identify individuals at high risk of HSIL. E6/E7 mRNA had the highest sensitivity for prevalent HSIL detection regardless of HIV status, whereas type 16 and/or 18 HPV DNA performed best in predicting development of incident HSIL within 12 months.

  15. Unchanged Levels of Soluble CD14 and IL-6 Over Time Predict Serious Non-AIDS Events in HIV-1-Infected People

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    Sunil, Meena; Nigalye, Maitreyee; Somasunderam, Anoma; Martinez, Maria Laura; Yu, Xiaoying; Arduino, Roberto C.; Bell, Tanvir K.

    2016-01-01

    Abstract HIV-1-infected persons have increased risk of serious non-AIDS events (SNAEs) despite suppressive antiretroviral therapy. Increased circulating levels of soluble CD14 (sCD14), soluble CD163 (sCD163), and interleukin-6 (IL-6) at a single time point have been associated with SNAEs. However, whether changes in these biomarker levels predict SNAEs in HIV-1-infected persons is unknown. We hypothesized that greater decreases in inflammatory biomarkers would be associated with fewer SNAEs. We identified 39 patients with SNAEs, including major cardiovascular events, end stage renal disease, decompensated cirrhosis, non-AIDS-defining malignancies, and death of unknown cause, and age- and sex-matched HIV-1-infected controls. sCD14, sCD163, and IL-6 were measured at study enrollment (T1) and proximal to the event (T2) or equivalent duration in matched controls. Over ∼34 months, unchanged rather than decreasing levels of sCD14 and IL-6 predicted SNAEs. Older age and current illicit substance abuse, but not HCV coinfection, were associated with SNAEs. In a multivariate analysis, older age, illicit substance use, and unchanged IL-6 levels remained significantly associated with SNAEs. Thus, the trajectories of sCD14 and IL-6 levels predict SNAEs. Interventions to decrease illicit substance use may decrease the risk of SNAEs in HIV-1-infected persons. PMID:27344921

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

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    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.

  17. Analysis of V2 antibody responses induced in vaccinees in the ALVAC/AIDSVAX HIV-1 vaccine efficacy trial.

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    Susan Zolla-Pazner

    Full Text Available The RV144 clinical trial of a prime/boost immunizing regimen using recombinant canary pox (ALVAC-HIV and two gp120 proteins (AIDSVAX B and E was previously shown to have a 31.2% efficacy rate. Plasma specimens from vaccine and placebo recipients were used in an extensive set of assays to identify correlates of HIV-1 infection risk. Of six primary variables that were studied, only one displayed a significant inverse correlation with risk of infection: the antibody (Ab response to a fusion protein containing the V1 and V2 regions of gp120 (gp70-V1V2. This finding prompted a thorough examination of the results generated with the complete panel of 13 assays measuring various V2 Abs in the stored plasma used in the initial pilot studies and those used in the subsequent case-control study. The studies revealed that the ALVAC-HIV/AIDSVAX vaccine induced V2-specific Abs that cross-react with multiple HIV-1 subgroups and recognize both conformational and linear epitopes. The conformational epitope was present on gp70-V1V2, while the predominant linear V2 epitope mapped to residues 165-178, immediately N-terminal to the putative α4β7 binding motif in the mid-loop region of V2. Odds ratios (ORs were calculated to compare the risk of infection with data from 12 V2 assays, and in 11 of these, the ORs were ≤1, reaching statistical significance for two of the variables: Ab responses to gp70-V1V2 and to overlapping V2 linear peptides. It remains to be determined whether anti-V2 Ab responses were directly responsible for the reduced infection rate in RV144 and whether anti-V2 Abs will prove to be important with other candidate HIV vaccines that show efficacy, however, the results support continued dissection of Ab responses to the V2 region which may illuminate mechanisms of protection from HIV-1 infection and may facilitate the development of an effective HIV-1 vaccine.

  18. Polyfunctional analysis of Gag and Nef specific CD8+ T-cell responses in HIV-1 infected Indian individuals.

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    Mendiratta, Sanjay; Vajpayee, Madhu; Mojumdar, Kamalika; Chauhan, Neeraj K; Sreenivas, Vishnubhatla

    2011-02-01

    Polyfunctional CD8+ T-cells have been described as most competent in controlling viral replication. We studied the impact of antigen persistence on the polyfunctional immune responses of CD8+ T-lymphocytes to HIV Gag and Nef peptides and polyclonal stimuli in 40 ART naïve HIV infected individuals and analyzed the alterations in T-cell functionality in early and late stages of infection. Significantly elevated level of global response and polyfunctional profile of CD8+ T-cells were observed to polyclonal stimulation, than HIV specific antigens in chronically infected individuals. However no key differences were observed in CD8+ T-cell functional profile in any of the 15 unique subsets for Gag and Nef specific antigens. The subjects in early stage of infection (defined as a gap of 6 months or less between seroconversion and enrolment and with no apparent clinical symptoms) had a higher degree of response functionality (4+ or 3+ different functions simultaneously) than in the late stage infection (defined as time duration since seroconversion greater than 6 months). The data suggest that persistence of antigen during chronic infection leads to functional impairment of HIV specific responses. Copyright © 2010 Elsevier Ltd. All rights reserved.

  19. Prediction of response to antiretroviral therapy by human experts and by the EuResist data-driven expert system (the EVE study).

    Science.gov (United States)

    Zazzi, M; Kaiser, R; Sönnerborg, A; Struck, D; Altmann, A; Prosperi, M; Rosen-Zvi, M; Petroczi, A; Peres, Y; Schülter, E; Boucher, C A; Brun-Vezinet, F; Harrigan, P R; Morris, L; Obermeier, M; Perno, C-F; Phanuphak, P; Pillay, D; Shafer, R W; Vandamme, A-M; van Laethem, K; Wensing, A M J; Lengauer, T; Incardona, F

    2011-04-01

    The EuResist expert system is a novel data-driven online system for computing the probability of 8-week success for any given pair of HIV-1 genotype and combination antiretroviral therapy regimen plus optional patient information. The objective of this study was to compare the EuResist system vs. human experts (EVE) for the ability to predict response to treatment. The EuResist system was compared with 10 HIV-1 drug resistance experts for the ability to predict 8-week response to 25 treatment cases derived from the EuResist database validation data set. All current and past patient data were made available to simulate clinical practice. The experts were asked to provide a qualitative and quantitative estimate of the probability of treatment success. There were 15 treatment successes and 10 treatment failures. In the classification task, the number of mislabelled cases was six for EuResist and 6-13 for the human experts [mean±standard deviation (SD) 9.1±1.9]. The accuracy of EuResist was higher than the average for the experts (0.76 vs. 0.64, respectively). The quantitative estimates computed by EuResist were significantly correlated (Pearson r=0.695, Pexperts. However, the agreement among experts was only moderate (for the classification task, inter-rater κ=0.355; for the quantitative estimation, mean±SD coefficient of variation=55.9±22.4%). With this limited data set, the EuResist engine performed comparably to or better than human experts. The system warrants further investigation as a treatment-decision support tool in clinical practice. © 2010 British HIV Association.

  20. Newborn Mice Vaccination with BCG.HIVA222 + MVA.HIVA Enhances HIV-1-Specific Immune Responses: Influence of Age and Immunization Routes

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    Narcís Saubi

    2011-01-01

    Full Text Available We have evaluated the influence of age and immunization routes for induction of HIV-1- and M. tuberculosis-specific immune responses after neonatal (7 days old and adult (7 weeks old BALB/c mice immunization with BCG.HIVA222 prime and MVA.HIVA boost. The specific HIV-1 cellular immune responses were analyzed in spleen cells. The body weight of the newborn mice was weekly recorded. The frequencies of HIV-specific CD8+ T cells producing IFN-γ were higher in adult mice vaccinated intradermally and lower in adult and newborn mice vaccinated subcutaneously. In all cases the IFN-γ production was significantly higher when mice were primed with BCG.HIVA222 compared with BCGwt. When the HIV-specific CTL activity was assessed, the frequencies of specific killing were higher in newborn mice than in adults. The prime-boost vaccination regimen which includes BCG.HIVA222 and MVA.HIVA was safe when inoculated to newborn mice. The administration of BCG.HIVA222 to newborn mice is safe and immunogenic and increased the HIV-specific responses induced by MVA.HIVA vaccine. It might be a good model for infant HIV and Tuberculosis bivalent vaccine.

  1. Newborn Mice Vaccination with BCG.HIVA222 + MVA.HIVA Enhances HIV-1-Specific Immune Responses: Influence of Age and Immunization Routes

    Science.gov (United States)

    Saubi, Narcís; Im, Eung-Jun; Fernández-Lloris, Raquel; Gil, Olga; Cardona, Pere-Joan; Gatell, Josep Maria; Hanke, Tomáš; Joseph, Joan

    2011-01-01

    We have evaluated the influence of age and immunization routes for induction of HIV-1- and M. tuberculosis-specific immune responses after neonatal (7 days old) and adult (7 weeks old) BALB/c mice immunization with BCG.HIVA222 prime and MVA.HIVA boost. The specific HIV-1 cellular immune responses were analyzed in spleen cells. The body weight of the newborn mice was weekly recorded. The frequencies of HIV-specific CD8+ T cells producing IFN-γ were higher in adult mice vaccinated intradermally and lower in adult and newborn mice vaccinated subcutaneously. In all cases the IFN-γ production was significantly higher when mice were primed with BCG.HIVA222 compared with BCGwt. When the HIV-specific CTL activity was assessed, the frequencies of specific killing were higher in newborn mice than in adults. The prime-boost vaccination regimen which includes BCG.HIVA222 and MVA.HIVA was safe when inoculated to newborn mice. The administration of BCG.HIVA222 to newborn mice is safe and immunogenic and increased the HIV-specific responses induced by MVA.HIVA vaccine. It might be a good model for infant HIV and Tuberculosis bivalent vaccine. PMID:21603216

  2. A vaccine encoding conserved promiscuous HIV CD4 epitopes induces broad T cell responses in mice transgenic to multiple common HLA class II molecules.

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    Susan Pereira Ribeiro

    Full Text Available Current HIV vaccine approaches are focused on immunogens encoding whole HIV antigenic proteins that mainly elicit cytotoxic CD8+ responses. Mounting evidence points toward a critical role for CD4+ T cells in the control of immunodeficiency virus replication, probably due to cognate help. Vaccine-induced CD4+ T cell responses might, therefore, have a protective effect in HIV replication. In addition, successful vaccines may have to elicit responses to multiple epitopes in a high proportion of vaccinees, to match the highly variable circulating strains of HIV. Using rational vaccine design, we developed a DNA vaccine encoding 18 algorithm-selected conserved, "promiscuous" (multiple HLA-DR-binding B-subtype HIV CD4 epitopes - previously found to be frequently recognized by HIV-infected patients. We assessed the ability of the vaccine to induce broad T cell responses in the context of multiple HLA class II molecules using different strains of HLA class II- transgenic mice (-DR2, -DR4, -DQ6 and -DQ8. Mice displayed CD4+ and CD8+ T cell responses of significant breadth and magnitude, and 16 out of the 18 encoded epitopes were recognized. By virtue of inducing broad responses against conserved CD4+ T cell epitopes that can be recognized in the context of widely diverse, common HLA class II alleles, this vaccine concept may cope both with HIV genetic variability and increased population coverage. The vaccine may thus be a source of cognate help for HIV-specific CD8+ T cells elicited by conventional immunogens, in a wide proportion of vaccinees.

  3. Does message framing predict willingness to participate in a hypothetical HIV vaccine trial: an application of Prospect Theory.

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    Evangeli, Michael; Kafaar, Zuhayr; Kagee, Ashraf; Swartz, Leslie; Bullemor-Day, Philippa

    2013-01-01

    It is vital that enough participants are willing to participate in clinical trials to test HIV vaccines adequately. It is, therefore, necessary to explore what affects peoples' willingness to participate (WTP) in such trials. Studies have only examined individual factors associated with WTP and not the effect of messages about trial participation on potential participants (e.g., whether losses or gains are emphasized, or whether the outcome is certain or uncertain). This study explores whether the effects of message framing on WTP in a hypothetical HIV vaccine trial are consistent with Prospect Theory. This theory suggests that people are fundamentally risk averse and that (1) under conditions of low risk and high certainty, gain-framed messages will be influential (2) under conditions of high risk and low certainty, loss-framed messages will be influential. This cross-sectional study recruited 283 HIV-negative students from a South African university who were given a questionnaire that contained matched certain gain-framed, certain loss-framed, uncertain gain-framed, and uncertain loss-framed statements based on common barriers and facilitators of WTP. Participants were asked to rate how likely each statement was to result in their participation in a hypothetical preventative HIV vaccine trial. Consistent with Prospect Theory predictions, for certain outcomes, gain-framed messages were more likely to result in WTP than loss-framed messages. Inconsistent with predictions, loss-framed message were not more likely to be related to WTP for uncertain outcomes than gain-framed messages. Older students were less likely to express their WTP across the different message frames. Recruitment for HIV vaccine trials should pay attention to how messages about the trial are presented to potential participants.

  4. Upregulation of Glucose Uptake and Hexokinase Activity of Primary Human CD4+ T Cells in Response to Infection with HIV-1

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    Maia Kavanagh Williamson

    2018-03-01

    Full Text Available Infection of primary CD4+ T cells with HIV-1 coincides with an increase in glycolysis. We investigated the expression of glucose transporters (GLUT and glycolytic enzymes in human CD4+ T cells in response to infection with HIV-1. We demonstrate the co-expression of GLUT1, GLUT3, GLUT4, and GLUT6 in human CD4+ T cells after activation, and their concerted overexpression in HIV-1 infected cells. The investigation of glycolytic enzymes demonstrated activation-dependent expression of hexokinases HK1 and HK2 in human CD4+ T cells, and a highly significant increase in cellular hexokinase enzyme activity in response to infection with HIV-1. HIV-1 infected CD4+ T cells showed a marked increase in expression of HK1, as well as the functionally related voltage-dependent anion channel (VDAC protein, but not HK2. The elevation of GLUT, HK1, and VDAC expression in HIV-1 infected cells mirrored replication kinetics and was dependent on virus replication, as evidenced by the use of reverse transcription inhibitors. Finally, we demonstrated that the upregulation of HK1 in HIV-1 infected CD4+ T cells is independent of the viral accessory proteins Vpu, Vif, Nef, and Vpr. Though these data are consistent with HIV-1 dependency on CD4+ T cell glucose metabolism, a cellular response mechanism to infection cannot be ruled out.

  5. High exposure to nevirapine in plasma is associated with an improved virological response in HIV-1-infected individuals

    NARCIS (Netherlands)

    Veldkamp, A. I.; Weverling, G. J.; Lange, J. M.; Montaner, J. S.; Reiss, P.; Cooper, D. A.; Vella, S.; Hall, D.; Beijnen, J. H.; Hoetelmans, R. M.

    2001-01-01

    OBJECTIVE: To explore relationships between exposure to nevirapine and the virological response in HIV-1-infected individuals participating in the INCAS trial. METHODS: The elimination rate constant of plasma HIV-1 RNA (k) was calculated during the first 2 weeks of treatment with nevirapine,

  6. Prediction of HIV-1 coreceptor usage (tropism) by sequence analysis using a genotypic approach.

    Science.gov (United States)

    Sierra, Saleta; Kaiser, Rolf; Lübke, Nadine; Thielen, Alexander; Schuelter, Eugen; Heger, Eva; Däumer, Martin; Reuter, Stefan; Esser, Stefan; Fätkenheuer, Gerd; Pfister, Herbert; Oette, Mark; Lengauer, Thomas

    2011-12-01

    Maraviroc (MVC) is the first licensed antiretroviral drug from the class of coreceptor antagonists. It binds to the host coreceptor CCR5, which is used by the majority of HIV strains in order to infect the human immune cells (Fig. 1). Other HIV isolates use a different coreceptor, the CXCR4. Which receptor is used, is determined in the virus by the Env protein (Fig. 2). Depending on the coreceptor used, the viruses are classified as R5 or X4, respectively. MVC binds to the CCR5 receptor inhibiting the entry of R5 viruses into the target cell. During the course of disease, X4 viruses may emerge and outgrow the R5 viruses. Determination of coreceptor usage (also called tropism) is therefore mandatory prior to administration of MVC, as demanded by EMA and FDA. The studies for MVC efficiency MOTIVATE, MERIT and 1029 have been performed with the Trofile assay from Monogram, San Francisco, U.S.A. This is a high quality assay based on sophisticated recombinant tests. The acceptance for this test for daily routine is rather low outside of the U.S.A., since the European physicians rather tend to work with decentralized expert laboratories, which also provide concomitant resistance testing. These laboratories have undergone several quality assurance evaluations, the last one being presented in 2011. For several years now, we have performed tropism determinations based on sequence analysis from the HIV env-V3 gene region (V3). This region carries enough information to perform a reliable prediction. The genotypic determination of coreceptor usage presents advantages such as: shorter turnover time (equivalent to resistance testing), lower costs, possibility to adapt the results to the patients' needs and possibility of analysing clinical samples with very low or even undetectable viral load (VL), particularly since the number of samples analysed with VL < 1000 copies/μl roughly increased in the last years (Fig. 3). The main steps for tropism testing (Fig. 4) demonstrated in

  7. Health systems' responses to 25 years of HIV in Europe: inequities persist and challenges remain.

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    Atun, Rifat A; McKee, Martin; Coker, Richard; Gurol-Urganci, Ipek

    2008-05-01

    Europe is currently experiencing the fastest rate of growth of HIV of any region of the world. An analysis of policy and health system responses to the HIV epidemic in Europe and central Asia (hereafter referred to as Europe) over the last 25 years reveals considerable heterogeneity. In general, while noting hazards of broad generalisations and the differences that exist across countries in a particular grouping, effective policies to control HIV have been implemented more widely in western than in central and eastern Europe. However, the evidence suggests persistence of inequalities in access to preventive and treatment services, with those at highest risk, such as commercial sex workers, prisoners, intravenous drug users, and migrants often particularly disadvantaged, despite many targeted programmes. Responses in individual countries, especially in the early stages of the epidemic, were influenced by specific cultural and political factors. Strong leadership and active involvement by civil society organisations emerge as important factors for success but also a limiting factor to the response observed in eastern Europe, where civil society or NGO culture is weak as compared to western Europe. Scaling up of effective responses in many countries in eastern Europe will be challenging-where increased financial resources will have to be accompanied by broader changes to health system organization with greater involvement of the civil society in planning and delivery of client-focused services.

  8. Impact of hepatitis B virus infection on HIV response to antiretroviral therapy in a Chinese antiretroviral therapy center

    Directory of Open Access Journals (Sweden)

    Rongrong Yang

    2014-11-01

    Conclusions: HBV co-infection can affect late immunological and virological responses to ART and increase the risk of hepatotoxicity. Mortality due to liver disease was high among HIV/HBV co-infected individuals in this study, despite HBV-active ART. As long as HIV/HBV co-infected persons need anti-HBV therapy, they should be recommended ART that includes agents with activity against both HIV and HBV, regardless of the CD4 cell count level.

  9. Risk factors of virologic failure and slow response to art among HIV ...

    African Journals Online (AJOL)

    Risk factors of virologic failure and slow response to art among HIV-infected children and adolescents in Nairobi. J. M. Kabogo, S. Gupta, A. K. Maina, M. Ochwoto, R. W. Omange, R. N. Musoke, R. W. Lihana, E. Muniu, F. W. Wamunyokoli, B. Liang, E. M. Songok ...

  10. HIV-1 p24(gag derived conserved element DNA vaccine increases the breadth of immune response in mice.

    Directory of Open Access Journals (Sweden)

    Viraj Kulkarni

    Full Text Available Viral diversity is considered a major impediment to the development of an effective HIV-1 vaccine. Despite this diversity, certain protein segments are nearly invariant across the known HIV-1 Group M sequences. We developed immunogens based on the highly conserved elements from the p24(gag region according to two principles: the immunogen must (i include strictly conserved elements of the virus that cannot mutate readily, and (ii exclude both HIV regions capable of mutating without limiting virus viability, and also immunodominant epitopes located in variable regions. We engineered two HIV-1 p24(gag DNA immunogens that express 7 highly Conserved Elements (CE of 12-24 amino acids in length and differ by only 1 amino acid in each CE ('toggle site', together covering >99% of the HIV-1 Group M sequences. Altering intracellular trafficking of the immunogens changed protein localization, stability, and also the nature of elicited immune responses. Immunization of C57BL/6 mice with p55(gag DNA induced poor, CD4(+ mediated cellular responses, to only 2 of the 7 CE; in contrast, vaccination with p24CE DNA induced cross-clade reactive, robust T cell responses to 4 of the 7 CE. The responses were multifunctional and composed of both CD4(+ and CD8(+ T cells with mature cytotoxic phenotype. These findings provide a method to increase immune response to universally conserved Gag epitopes, using the p24CE immunogen. p24CE DNA vaccination induced humoral immune responses similar in magnitude to those induced by p55(gag, which recognize the virus encoded p24(gag protein. The inclusion of DNA immunogens composed of conserved elements is a promising vaccine strategy to induce broader immunity by CD4(+ and CD8(+ T cells to additional regions of Gag compared to vaccination with p55(gag DNA, achieving maximal cross-clade reactive cellular and humoral responses.

  11. IgM response to a human Pneumocystis carinii surface antigen in HIV-infected patients with pulmonary symptoms

    DEFF Research Database (Denmark)

    Lundgren, Bettina; Kovacs, J A; Mathiesen, Lars Reinhardt

    1993-01-01

    We have developed an ELISA to detect IgM antibodies to a major human Pneumocystis carinii surface antigen (gp95), and investigated the IgM response in 128 HIV-infected patients who underwent bronchoscopy for evaluation of pulmonary symptoms. Only 5 (4%) patients had IgM antibodies to P. carinii gp...... response to gp95. These patients also showed an increase in IgG antibodies to gp95 and had microbiologically proven PCP. Prior to the development of the IgM response, IgG antibodies to gp95 were detectable in all 3 patients. Thus, HIV-infected patients with PCP seldom produce IgM antibodies to the major...

  12. Responsiveness to HIV education and VCT services among Kenyan rural women: a community-based survey.

    Science.gov (United States)

    Karau, Paul Bundi; Winnie, Mueni Saumu; Geoffrey, Muriira; Mwenda, Mukuthuria

    2010-09-01

    Uptake of VCT and other HIV prevention strategies among rural African women is affected by various socio-cultural and economic factors which need elucidation. Our aim was to establish the responsiveness to HIV education among rural women attending three dispensaries in Kenya. This study was designed to assess gender and psycho-social factors that influence HIV dynamics in rural Kenya. This was a cross-sectional questionnaire based study of 1347 women, conducted in October 2009. Socio-economic status as well as knowledge on methods of HIV transmission was assessed. Testing status, knowledge on existing VCT services and willingness to share HIV information with their children was assessed. Majority of the women have heard about VCT services, but significantly few of them have been tested. Those with secondary school education and above are more knowledgeable on methods of HIV transmission, while those with inadequate education are more likely to cite shaking hands, sharing utensils, mosquito bites and hugging as means of transmission (p = 0.001). 90% of educated women are willing to share HIV information with their children, compared to 40% of uneducated women. Marital status is seen to positively influence testing status, but has no significant effect on dissemination of information to children. We conclude that despite the aggressive HIV education and proliferation of VCT services in Kenya, women are not heeding the call to get tested. Education has a positive impact on dissemination of HIV information. Focus needs to shift into increasing acceptability of testing by women in rural Kenya.

  13. Reviewing independent access to HIV testing, counselling and treatment for adolescents in HIV-specific laws in sub-Saharan Africa: implications for the HIV response

    Science.gov (United States)

    Eba, Patrick M.; Lim, HyeYoung

    2017-01-01

    Abstract Introduction: AIDS is a leading cause of death among adolescents in sub-Saharan Africa. Yet, legal, policy and social barriers continue to restrict their access to HIV services. In recent years, access to independent HIV testing and treatment for adolescents has gained increased attention. The 2013 WHO Guidance on HIV testing and counselling and care for adolescents living with HIV (WHO Guidance) calls for reviewing legal and regulatory frameworks to facilitate adolescents’ access to comprehensive HIV services. As of 31 March 2017, some 28 countries in sub-Saharan Africa have adopted HIV-specific legislation. But there is limited understanding of the provisions of these laws on access to HIV services for adolescents and their implication on efforts to scale up HIV prevention, testing, treatment and care among this population. Methods: A desk review of 28 HIV-specific laws in sub-Saharan Africa complemented with the review of HIV testing policies in four countries using human rights norms and key public health recommendations from the 2013 WHO Guidance. These recommendations call on countries to (i) lower the age of consent to HIV testing and counselling and allow mature adolescents who have not reached the age of consent to independently access HIV testing, (ii) ensure access to HIV counselling for adolescents, (iii) protect the confidentiality of adolescents living with HIV and (iv) facilitate access to HIV treatment for adolescents living with HIV. Results: Most HIV-specific laws fail to take into account human rights principles and public health recommendations for facilitating adolescents’ access to HIV services. None of the countries with HIV-specific laws has adopted all four recommendations for access to HIV services for adolescents. Discrepancies exist between HIV laws and national policy documents. Inadequate and conflicting provisions in HIV laws are likely to hinder access to HIV testing, counselling and treatment for adolescents

  14. Reviewing independent access to HIV testing, counselling and treatment for adolescents in HIV-specific laws in sub-Saharan Africa: implications for the HIV response.

    Science.gov (United States)

    Eba, Patrick M; Lim, HyeYoung

    2017-08-11

    AIDS is a leading cause of death among adolescents in sub-Saharan Africa. Yet, legal, policy and social barriers continue to restrict their access to HIV services. In recent years, access to independent HIV testing and treatment for adolescents has gained increased attention. The 2013 WHO Guidance on HIV testing and counselling and care for adolescents living with HIV (WHO Guidance) calls for reviewing legal and regulatory frameworks to facilitate adolescents' access to comprehensive HIV services. As of 31 March 2017, some 28 countries in sub-Saharan Africa have adopted HIV-specific legislation. But there is limited understanding of the provisions of these laws on access to HIV services for adolescents and their implication on efforts to scale up HIV prevention, testing, treatment and care among this population. A desk review of 28 HIV-specific laws in sub-Saharan Africa complemented with the review of HIV testing policies in four countries using human rights norms and key public health recommendations from the 2013 WHO Guidance. These recommendations call on countries to (i) lower the age of consent to HIV testing and counselling and allow mature adolescents who have not reached the age of consent to independently access HIV testing, (ii) ensure access to HIV counselling for adolescents, (iii) protect the confidentiality of adolescents living with HIV and (iv) facilitate access to HIV treatment for adolescents living with HIV. Most HIV-specific laws fail to take into account human rights principles and public health recommendations for facilitating adolescents' access to HIV services. None of the countries with HIV-specific laws has adopted all four recommendations for access to HIV services for adolescents. Discrepancies exist between HIV laws and national policy documents. Inadequate and conflicting provisions in HIV laws are likely to hinder access to HIV testing, counselling and treatment for adolescents. Efforts to end legal barriers to access to HIV services

  15. Mosaic HIV envelope immunogenic polypeptides

    Science.gov (United States)

    Korber, Bette T. M.; Gnanakaran, S.; Perkins, Simon; Sodroski, Joseph; Haynes, Barton

    2018-01-02

    Disclosed herein are mosaic HIV envelope (Env) polypeptides that can elicit an immune response to HIV (such as cytotoxic T cell (CTL), helper T cell, and/or humoral responses). Also disclosed are sets of the disclosed mosaic Env polypeptides, which include two or more (for example, three) of the polypeptides. Also disclosed herein are methods for treating or inhibiting HIV in a subject including administering one or more of the disclosed immunogenic polypeptides or compositions to a subject infected with HIV or at risk of HIV infection. In some embodiments, the methods include inducing an immune response to HIV in a subject comprising administering to the subject at least one (such as two, three, or more) of the immunogenic polypeptides or at least one (such as two, three, or more) nucleic acids encoding at least one of the immunogenic polypeptides disclosed herein.

  16. HIV/AIDS knowledge among men who have sex with men: applying the item response theory.

    Science.gov (United States)

    Gomes, Raquel Regina de Freitas Magalhães; Batista, José Rodrigues; Ceccato, Maria das Graças Braga; Kerr, Lígia Regina Franco Sansigolo; Guimarães, Mark Drew Crosland

    2014-04-01

    To evaluate the level of HIV/AIDS knowledge among men who have sex with men in Brazil using the latent trait model estimated by Item Response Theory. Multicenter, cross-sectional study, carried out in ten Brazilian cities between 2008 and 2009. Adult men who have sex with men were recruited (n = 3,746) through Respondent Driven Sampling. HIV/AIDS knowledge was ascertained through ten statements by face-to-face interview and latent scores were obtained through two-parameter logistic modeling (difficulty and discrimination) using Item Response Theory. Differential item functioning was used to examine each item characteristic curve by age and schooling. Overall, the HIV/AIDS knowledge scores using Item Response Theory did not exceed 6.0 (scale 0-10), with mean and median values of 5.0 (SD = 0.9) and 5.3, respectively, with 40.7% of the sample with knowledge levels below the average. Some beliefs still exist in this population regarding the transmission of the virus by insect bites, by using public restrooms, and by sharing utensils during meals. With regard to the difficulty and discrimination parameters, eight items were located below the mean of the scale and were considered very easy, and four items presented very low discrimination parameter (items contributed to the inaccuracy of the measurement of knowledge among those with median level and above. Item Response Theory analysis, which focuses on the individual properties of each item, allows measures to be obtained that do not vary or depend on the questionnaire, which provides better ascertainment and accuracy of knowledge scores. Valid and reliable scales are essential for monitoring HIV/AIDS knowledge among the men who have sex with men population over time and in different geographic regions, and this psychometric model brings this advantage.

  17. Understanding HIV infection for the design of a therapeutic vaccine. Part II: Vaccination strategies for HIV.

    Science.gov (United States)

    de Goede, A L; Vulto, A G; Osterhaus, A D M E; Gruters, R A

    2015-05-01

    HIV infection leads to a gradual loss CD4(+) T lymphocytes comprising immune competence and progression to AIDS. Effective treatment with combined antiretroviral drugs (cART) decreases viral load below detectable levels but is not able to eliminate the virus from the body. The success of cART is frustrated by the requirement of expensive lifelong adherence, accumulating drug toxicities and chronic immune activation resulting in increased risk of several non-AIDS disorders, even when viral replication is suppressed. Therefore, there is a strong need for therapeutic strategies as an alternative to cART. Immunotherapy, or therapeutic vaccination, aims to increase existing immune responses against HIV or induce de novo immune responses. These immune responses should provide a functional cure by controlling viral replication and preventing disease progression in the absence of cART. The key difficulty in the development of an HIV vaccine is our ignorance of the immune responses that control of viral replication, and thus how these responses can be elicited and how they can be monitored. Part one of this review provides an extensive overview of the (patho-) physiology of HIV infection. It describes the structure and replication cycle of HIV, the epidemiology and pathogenesis of HIV infection and the innate and adaptive immune responses against HIV. Part two of this review discusses therapeutic options for HIV. Prevention modalities and antiretroviral therapy are briefly touched upon, after which an extensive overview on vaccination strategies for HIV is provided, including the choice of immunogens and delivery strategies. Copyright © 2014. Published by Elsevier Masson SAS.

  18. HIV-1 vaccines

    Science.gov (United States)

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

    2014-01-01

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

  19. Evaluating HIV Knowledge Questionnaires Among Men Who Have Sex with Men: A Multi-Study Item Response Theory Analysis.

    Science.gov (United States)

    Janulis, Patrick; Newcomb, Michael E; Sullivan, Patrick; Mustanski, Brian

    2018-01-01

    Knowledge about the transmission, prevention, and treatment of HIV remains a critical element in psychosocial models of HIV risk behavior and is commonly used as an outcome in HIV prevention interventions. However, most HIV knowledge questions have not undergone rigorous psychometric testing such as using item response theory. The current study used data from six studies of men who have sex with men (MSM; n = 3565) to (1) examine the item properties of HIV knowledge questions, (2) test for differential item functioning on commonly studied characteristics (i.e., age, race/ethnicity, and HIV risk behavior), (3) select items with the optimal item characteristics, and (4) leverage this combined dataset to examine the potential moderating effect of age on the relationship between condomless anal sex (CAS) and HIV knowledge. Findings indicated that existing questions tend to poorly differentiate those with higher levels of HIV knowledge, but items were relatively robust across diverse individuals. Furthermore, age moderated the relationship between CAS and HIV knowledge with older MSM having the strongest association. These findings suggest that additional items are required in order to capture a more nuanced understanding of HIV knowledge and that the association between CAS and HIV knowledge may vary by age.

  20. The role of fear in predicting sexually transmitted infection screening.

    Science.gov (United States)

    Shepherd, Lee; Smith, Michael A

    2017-07-01

    This study assessed the extent to which social-cognitive factors (attitude, subjective norm and perceived control) and the fear of a positive test result predict sexually transmitted infection (STI) screening intentions and subsequent behaviour. Study 1 (N = 85) used a longitudinal design to assess the factors that predict STI screening intention and future screening behaviour measured one month later at Time 2. Study 2 (N = 102) used an experimental design to determine whether the relationship between fear and screening varied depending on whether STI or HIV screening was being assessed both before and after controlling for social-cognitive factors. Across the studies the outcome measures were sexual health screening. In both studies, the fear of having an STI positively predicted STI screening intention. In Study 1, fear, but not the social-cognitive factors, also predicted subsequent STI screening behaviour. In Study 2, the fear of having HIV did not predict HIV screening intention, but attitude negatively and response efficacy positively predicted screening intention. This study highlights the importance of considering the nature of the health condition when assessing the role of fear on health promotion.

  1. Assessing business responses to HIV / AIDS in Kenya.

    Science.gov (United States)

    Roberts, M; Wangombe, J

    1995-01-01

    A consulting firm conducted interviews with managers of 16 businesses in 3 Kenyan cities, representatives of 2 trade unions, focus groups with workers at 13 companies, and an analysis of financial/labor data from 4 companies. It then did a needs assessment. The business types were light industry, manufacturing companies, tourism organizations, transport firms, agro-industrial and plantation businesses, and the service industry. Only one company followed all the workplace policy principles recommended by the World Health Organization and the International Labor Organization. Six businesses required all applicants and/or employees to undergo HIV testing. All their managers claimed that they would not discriminate against HIV-infected workers. Many workers thought that they would be fired if they were--or were suspected to be--HIV positive. Lack of a non-discrimination policy brings about worker mistrust of management. 11 companies had some type of HIV/AIDS education program. All the programs generated positive feedback. The main reasons for not providing HIV/AIDS education for the remaining 5 companies were: no employee requests, fears that it would be taboo, and assumptions that workers could receive adequate information elsewhere. More than 90% of all companies distributed condoms. 60% offered sexually transmitted disease diagnosis and treatment. About 33% offered counseling. Four companies provided volunteer HIV testing. Almost 50% of companies received financial or other external support for their programs. Most managers thought AIDS to be a problem mainly with manual staff and not with professional staff. Almost all businesses offered some medical benefits. The future impact of HIV/AIDS would be $90/employee/year (by 2005, $260) due to health care costs, absenteeism, retraining, and burial benefits. The annual costs of a comprehensive workplace HIV/AIDS prevention program varied from $18 to $54/worker at one company.

  2. Appraising the performance of genotyping tools in the prediction of coreceptor tropism in HIV-1 subtype C viruses

    Directory of Open Access Journals (Sweden)

    Crous Saleema

    2012-09-01

    Full Text Available Abstract Background In human immunodeficiency virus type 1 (HIV-1 infection, transmitted viruses generally use the CCR5 chemokine receptor as a coreceptor for host cell entry. In more than 50% of subtype B infections, a switch in coreceptor tropism from CCR5- to CXCR4-use occurs during disease progression. Phenotypic or genotypic approaches can be used to test for the presence of CXCR4-using viral variants in an individual’s viral population that would result in resistance to treatment with CCR5-antagonists. While genotyping approaches for coreceptor-tropism prediction in subtype B are well established and verified, they are less so for subtype C. Methods Here, using a dataset comprising V3 loop sequences from 349 CCR5-using and 56 CXCR4-using HIV-1 subtype C viruses we perform a comparative analysis of the predictive ability of 11 genotypic algorithms in their prediction of coreceptor tropism in subtype C. We calculate the sensitivity and specificity of each of the approaches as well as determining their overall accuracy. By separating the CXCR4-using viruses into CXCR4-exclusive (25 sequences and dual-tropic (31 sequences we evaluate the effect of the possible conflicting signal from dual-tropic viruses on the ability of a of the approaches to correctly predict coreceptor phenotype. Results We determined that geno2pheno with a false positive rate of 5% is the best approach for predicting CXCR4-usage in subtype C sequences with an accuracy of 94% (89% sensitivity and 99% specificity. Contrary to what has been reported for subtype B, the optimal approaches for prediction of CXCR4-usage in sequence from viruses that use CXCR4 exclusively, also perform best at predicting CXCR4-use in dual-tropic viral variants. Conclusions The accuracy of genotyping approaches at correctly predicting the coreceptor usage of V3 sequences from subtype C viruses is very high. We suggest that genotyping approaches can be used to test for coreceptor tropism in HIV-1

  3. Addressing gender inequality and intimate partner violence as critical barriers to an effective HIV response in sub-Saharan Africa

    OpenAIRE

    Watts, Charlotte; Seeley, Janet

    2014-01-01

    Introduction: In Africa, women and girls represent 57% of people living with HIV, with gender inequality and violence being an important structural determinant of their vulnerability. This commentary draws out lessons for a more effective combination response to the HIV epidemic from three papers recently published in JIAS. Discussion: Hatcher and colleagues present qualitative data from women attending ante-natal clinics in Johannesburg, describing how HIV diagnosis during pregnancy and subs...

  4. Development of Broadly Neutralizing Antibody Mimitopes for Characterization of CRF01_AE HIV-1 Antibody Responses

    Directory of Open Access Journals (Sweden)

    Jesse V. Schoen

    2017-10-01

    Full Text Available Mapping humoral immune responses to HIV-1 over the course of natural infection is important in understanding epitope exposure in relation to elicitation of broadly neutralizing antibodies (bNAbs, which is considered imperative for effective vaccine design. When analyzing HIV-specific immune responses, the antibody binding profiles may be a correlate for functional antibody activity. In this study, we utilized phage display technology to identify novel mimitopes that may represent Env epitope structures bound by bNAbs directed at V1V2 and V3 domains, CD4 binding site (CD4bs and the membrane proximal external region (MPER of Env. Mimitope sequence motifs were determined for each bNAb epitope. Given the ongoing vaccine development efforts in Thailand, these mimitopes that represent CD4bs and MPER epitopes were used to map immune responses of HIV-1 CRF01_AE-infected individuals with known neutralizing responses from two distinct time periods, 1996-98 and 2012-15. The more contemporary cohort showed an increase in binding breadth with binding observed for all MPER and CD4bs mimitopes, while the older cohort showed only 75% recognition of the CD4bs mimitopes and no MPER mimotope binding. Furthermore, mimitope binding profiles correlated significantly with magnitude (p=0.0036 and breadth (p=0.0358 of neutralization of a multi-subtype Tier 1 panel of pseudoviruses. These results highlight the utility of this mimitope mapping approach for detecting human plasma IgG-specificities that target known neutralizing antibody epitopes, and may also provide an indication of the plasticity of antibody binding within HIV-1 Env neutralization determinants.

  5. A critical public-health ethics analysis of Canada's international response to HIV.

    Science.gov (United States)

    Nixon, Stephanie A; Benatar, Solomon R

    2011-01-01

    As interconnections between health, ideology and politics become increasingly acknowledged, gaps in the literature also become visible in terms of analytic frameworks to engage these issues and empirical studies to understand the complexities. 'Critical public-health ethics' provides such an analytic lens. This article presents the results of a critical public-health ethics analysis of the government of Canada's international response to HIV. This qualitative study involved in-depth, semi-structured interviews with 23 experts on Canada's international response over time. Descriptive, thematic and theoretical analyses revealed an underlying dilemma between Canada's philanthropic desire to 'do the right thing' for the broader public good and Canada's commitment to its own economic growth and other forms of self-interest. Related to this tension were four conspicuous areas of silence in the data: (1) The relative absence of moral vocabulary for discussing Canada's duty to respond to the global HIV pandemic. (2) Scant reference to solutions based on poverty reduction. (3) Little awareness about the dominance of neoliberal economic rationality and its impact on HIV. (4) Limited understanding of Canada's function within the international economic order in terms of its role in poverty creation. Our study has implications for Canada and other rich nations through its empirical contribution to the chorus of calls challenging the legitimised, institutionalised and normative practice of considering the economic growth of wealthy countries as the primary objective of global economic policy.

  6. [Facing the HIV/AIDS epidemic in Mexico: the response of the health sector].

    Science.gov (United States)

    Gutiérrez, Juan Pablo; López-Zaragoza, José Luis; Valencia-Mendoza, Atanacio; Pesqueira, Eduardo; Ponce-de-León, Samuel; Bertozzi, Stefano M

    2004-01-01

    To analyze the challenges and accomplishments of the Mexican health system as it faced the HIV/AIDS epidemic over the 20 years since discovery of the virus. A review of the relevant literature was done. The topics revised were: HIV/AIDS epidemiology, the early response of the health system and civil society, prevention and risk behaviors, care and treatment, and financing and resources allocation. In Mexico a rapid initial public response surely contributed to containing any early spread of the epidemic to select populations; whether that spread will continue to be contained is an open question. Sexual risk practices remain high not only among traditional risk populations but also among youth. Even though the epidemic remains concentrated in Mexico, principally among MSM and IDU, only 13% of public HIV prevention funds are directed to key populations at especially high risk of becoming infected or infecting others. In recent years antiretroviral coverage has increased rapidly with funding increasing from 30 to 367 million pesos from 2001 to 2003 and coverage now approaching 100%. Of all health spending on HIV/AIDS in the public sector, 82.4% is spent by the social security institutes and 17.6% by the Ministry of Health. The former provides medical care to about half of PLHA while the latter, in addition to caring for the other half, supports the large majority of prevention expenses. One of the challenges faced by the health system which has largely achieved universal antiretroviral coverage is how to provide quality care with appropriate monitoring, promotion of adherence and recognition and treatment of resistance and adverse effects--without dramatically increasing costs.

  7. Broad CTL response is required to clear latent HIV-1 due to dominance of escape mutations

    Science.gov (United States)

    Deng, Kai; Pertea, Mihaela; Rongvaux, Anthony; Wang, Leyao; Durand, Christine M.; Ghiaur, Gabriel; Lai, Jun; McHugh, Holly L.; Hao, Haiping; Zhang, Hao; Margolick, Joseph B.; Gurer, Cagan; Murphy, Andrew J.; Valenzuela, David M.; Yancopoulos, George D.; Deeks, Steven G.; Strowig, Till; Kumar, Priti; Siliciano, Janet D.; Salzberg, Steven L.; Flavell, Richard A.; Shan, Liang; Siliciano, Robert F.

    2015-01-01

    Despite antiretroviral therapy (ART), HIV-1 persists in a stable latent reservoir1, 2, primarily in resting memory CD4+ T cells3, 4. This reservoir presents a major barrier to the cure of HIV-1 infection. To purge the reservoir, pharmacological reactivation of latent HIV-1 has been proposed5 and tested both in vitro and in vivo6–8. A key remaining question is whether virus-specific immune mechanisms including cytolytic T lymphocytes (CTL) can clear infected cells in ART-treated patients after latency is reversed. Here we show that there is a striking all or none pattern for CTL escape mutations in HIV-1 Gag epitopes. Unless ART is started early, the vast majority (>98%) of latent viruses carry CTL escape mutations that render infected cells insensitive to CTLs directed at common epitopes. To solve this problem, we identified CTLs that could recognize epitopes from latent HIV-1 that were unmutated in every chronically infected patient tested. Upon stimulation, these CTLs eliminated target cells infected with autologous virus derived from the latent reservoir, both in vitro and in patient-derived humanized mice. The predominance of CTL-resistant viruses in the latent reservoir poses a major challenge to viral eradication. Our results demonstrate that chronically infected patients retain a broad spectrum viral-specific CTL response and that appropriate boosting of this response may be required for the elimination of the latent reservoir. PMID:25561180

  8. Poor CD4 response despite viral suppression is associated with increased non-AIDS related mortality among HIV patients and their parents

    DEFF Research Database (Denmark)

    Helleberg, Marie; Kronborg, Gitte; Larsen, Carsten S

    2012-01-01

    association between poor CD4 response and increased risk of cardiovascular disease and cancer (IRR 1.6 (95%CI 0.8-3.2) and 1.6 (95%CI 0.6-4.8)). CONCLUSIONS:: poor CD4 increase after HAART is associated with adverse prognosis even in absence of severe immunosuppression. CD4 response in HIV patients......INTRODUCTION:: poor CD4 response to antiretroviral treatment (HAART) is associated with increased mortality. We analyzed the impact of CD4 increase on non-AIDS related morbidity and on mortality in HIV patients and their parents. METHODS:: mortality rates were estimated among 1,758 virally...... is associated with mortality among their parents, thus poor CD4 response may be caused by genetic factors, which might also affect morbidity and mortality in the HIV negative population....

  9. Risk Factors for HIV Transmission and Barriers to HIV Disclosure: Metropolitan Atlanta Youth Perspectives.

    Science.gov (United States)

    Camacho-Gonzalez, Andres F; Wallins, Amy; Toledo, Lauren; Murray, Ashley; Gaul, Zaneta; Sutton, Madeline Y; Gillespie, Scott; Leong, Traci; Graves, Chanda; Chakraborty, Rana

    2016-01-01

    Youth carry the highest incidence of HIV infection in the United States. Understanding adolescent and young adult (AYA) perspectives on HIV transmission risk is important for targeted HIV prevention. We conducted a mixed methods study with HIV-infected and uninfected youth, ages 18-24 years, from Atlanta, GA. We provided self-administered surveys to HIV-infected and HIV-uninfected AYAs to identify risk factors for HIV acquisition. By means of computer-assisted thematic analyses, we examined transcribed focus group responses on HIV education, contributors to HIV transmission, and pre-sex HIV status disclosure. The 68 participants had the following characteristics: mean age 21.5 years (standard deviation: 1.8 years), 85% male, 90% black, 68% HIV-infected. HIV risk behaviors included the perception of condomless sex (Likert scale mean: 8.0) and transactional sex (88% of participants); no differences were noted by HIV status. Qualitative analyses revealed two main themes: (1) HIV risk factors among AYAs, and (2) barriers to discussing HIV status before sex. Participants felt the use of social media, need for immediate gratification, and lack of concern about HIV disease were risk factors for AYAs. Discussing HIV status with sex partners was uncommon. Key reasons included: fear of rejection, lack of confidentiality, discussion was unnecessary in temporary relationships, and disclosure negatively affecting the mood. HIV prevention strategies for AYAs should include improving condom use frequency and HIV disclosure skills, responsible utilization of social media, and education addressing HIV prevention including the risks of transactional sex.

  10. Indikatorsygdomme for hiv-infektion

    DEFF Research Database (Denmark)

    Hansen, Birgitte Rønde; Andersen, Åse Bengård; Koch, Anders

    2015-01-01

    The mortality of HIV-infected patients in Denmark approaches that of the background population. Still, half of the HIV-infected patients are diagnosed late, resulting in poorer response to therapy, larger cost and greater transmission rate. A pan-European initiative, "HIV in Europe" has published...... a guideline on indicator-based HIV testing in order to improve early HIV diagnosis. The Danish Society of Infectious Diseases wishes to highlight the importance of indicator-based HIV testing, in order to improve the possibility of early diagnosis and therapy of HIV-infection....

  11. Differences in serum IgA responses to HIV-1 gp41 in elite controllers compared to viral suppressors on highly active antiretroviral therapy.

    Directory of Open Access Journals (Sweden)

    Rafiq Nabi

    Full Text Available Mechanisms responsible for natural control of human immunodeficiency type 1 (HIV replication in elite controllers (EC remain incompletely defined. To determine if EC generate high quality HIV-specific IgA responses, we used Western blotting to compare the specificities and frequencies of IgA to HIV antigens in serum of gender-, age- and race-matched EC and aviremic controllers (HC and viremic noncontrollers (HN on highly active antiretroviral therapy (HAART. Concentrations and avidity of IgA to HIV antigens were measured using ELISA or multiplex assays. Measurements for IgG were performed in parallel. EC were found to have stronger p24- and V1V2-specific IgG responses than HN, but there were no IgG differences for EC and HC. In contrast, IgA in EC serum bound more frequently to gp160 and gag proteins than IgA in HC or HN. The avidity of anti-gp41 IgA was also greater in EC, and these subjects had stronger IgA responses to the gp41 heptad repeat region 1 (HR1, a reported target of anti-bacterial RNA polymerase antibodies that cross react with gp41. However, EC did not demonstrate greater IgA responses to E. coli RNA polymerase or to peptides containing the shared LRAI sequence, suggesting that most of their HR1-specific IgA antibodies were not induced by intestinal microbiota. In both EC and HAART recipients, the concentrations of HIV-specific IgG were greater than HIV-specific IgA, but their avidities were comparable, implying that they could compete for antigen. Exceptions were C1 peptides and V1V2 loops. IgG and IgA responses to these antigens were discordant, with IgG reacting to V1V2, and IgA reacting to C1, especially in EC. Interestingly, EC with IgG hypergammaglobulinemia had greater HIV-specific IgA and IgG responses than EC with normal total IgG levels. Heterogeneity in EC antibody responses may therefore be due to a more focused HIV-specific B cell response in some of these individuals. Overall, these data suggest that development of

  12. Reevaluation of immune activation in the era of cART and an aging HIV-infected population.

    Science.gov (United States)

    de Armas, Lesley R; Pallikkuth, Suresh; George, Varghese; Rinaldi, Stefano; Pahwa, Rajendra; Arheart, Kristopher L; Pahwa, Savita

    2017-10-19

    Biological aging is associated with immune activation (IA) and declining immunity due to systemic inflammation. It is widely accepted that HIV infection causes persistent IA and premature immune senescence despite effective antiretroviral therapy and virologic suppression; however, the effects of combined HIV infection and aging are not well defined. Here, we assessed the relationship between markers of IA and inflammation during biological aging in HIV-infected and -uninfected populations. Antibody response to seasonal influenza vaccination was implemented as a measure of immune competence and relationships between IA, inflammation, and antibody responses were explored using statistical modeling appropriate for integrating high-dimensional data sets. Our results show that markers of IA, such as coexpression of HLA antigen D related (HLA-DR) and CD38 on CD4+ T cells, exhibit strong associations with HIV infection but not with biological age. Certain variables that showed a strong relationship with aging, such as declining naive and CD38+ CD4 and CD8+ T cells, did so regardless of HIV infection. Interestingly, the variable of biological age was not identified in a predictive model as significantly impacting vaccine responses in either group, while distinct IA and inflammatory variables were closely associated with vaccine response in HIV-infected and -uninfected populations. These findings shed light on the most relevant and persistent immune defects during virological suppression with antiretroviral therapy.

  13. Delayed-type hypersensitivity skin test responses to PPD and other antigens among BCG-vaccinated HIV-1-infected and healthy children and adolescents.

    Science.gov (United States)

    Costa, Natalia Moriya Xavierda; Albuquerque, Maly de; Lins, Janaína Bacelar Acioli; Alvares-Junior, João Teixeira; Stefani, Mariane Martins de Araújo

    2011-10-01

    Among HIV-1-infected patients, CD4+ T cell counts are well-established markers of cell-mediated immunity. Delayed-type hypersensitivity (DTH) skin tests can be used to evaluate in vivo cell-mediated immunity to common antigens. DTH responses to tuberculin purified protein derivative (PPD), sporotrichin, trichophytin, candidin and streptokinase/streptodornase antigens were assessed. Thirty-six HIV-1-infected children/adolescents and 56 age- and sex-matched HIV-1/HIV-2-seronegative participants were tested. All participants had a BCG scar. Fisher's exact test was used to evaluate significant differences between groups (pPPD positivity prevailed among healthy participants (40/56, 71.4%). PPD reactivity in the HIV-1-positive group was 8.3% (pPPD induration was 2.5mm (range: 2-5mm) in the HIV-1 group and 6.0 mm among healthy participants (range: 3-15 mm). There was no correlation between PPD positivity and age. No correlation between CD4+ T cell counts and DTH reactivity was observed among HIV-1-infected patients. DTH skin test responses, including PPD reactivity, were significantly lower among HIV-1-infected participants compared to healthy controls, which likely reflects advanced disease and T cell depletion.

  14. Reference curves for CD4 T-cell count response to combination antiretroviral therapy in HIV-1-infected treatment-naïve patients

    DEFF Research Database (Denmark)

    Bouteloup, V; Sabin, C; Mocroft, A

    2017-01-01

    OBJECTIVES: The aim of this work was to provide a reference for the CD4 T-cell count response in the early months after the initiation of combination antiretroviral therapy (cART) in HIV-1-infected patients. METHODS: All patients in the Collaboration of Observational HIV Epidemiological Research....... Unadjusted and adjusted references curves and predictions were obtained using quantile regressions. RESULTS: A total of 28 992 patients were included in the study. The median CD4 T-cell count at treatment initiation was 249 [interquartile range (IQR) 150, 336] cells/μL. The median observed CD4 counts at 6, 9...... and 12 months were 382 (IQR 256, 515), 402 (IQR 274, 543) and 420 (IQR 293, 565) cells/μL. The two main factors explaining the variation of CD4 count at 6 months were AIDS stage and CD4 count at cART initiation. A CD4 count increase of ≥ 100 cells/mL is generally required in order that patients stay 'on...

  15. Computational models as predictors of HIV treatment outcomes for the Phidisa cohort in South Africa

    Directory of Open Access Journals (Sweden)

    Andrew Revell

    2016-06-01

    Full Text Available Background: Selecting the optimal combination of HIV drugs for an individual in resourcelimited settings is challenging because of the limited availability of drugs and genotyping. Objective: The evaluation as a potential treatment support tool of computational models that predict response to therapy without a genotype, using cases from the Phidisa cohort in South Africa. Methods: Cases from Phidisa of treatment change following failure were identified that had the following data available: baseline CD4 count and viral load, details of failing and previous antiretroviral drugs, drugs in new regimen and time to follow-up. The HIV Resistance Response Database Initiative’s (RDI’s models used these data to predict the probability of a viral load < 50 copies/mL at follow-up. The models were also used to identify effective alternative combinations of three locally available drugs. Results: The models achieved accuracy (area under the receiver–operator characteristic curve of 0.72 when predicting response to therapy, which is less accurate than for an independent global test set (0.80 but at least comparable to that of genotyping with rules-based interpretation. The models were able to identify alternative locally available three-drug regimens that were predicted to be effective in 69% of all cases and 62% of those whose new treatment failed in the clinic. Conclusion: The predictive accuracy of the models for these South African patients together with the results of previous studies suggest that the RDI’s models have the potential to optimise treatment selection and reduce virological failure in different patient populations, without the use of a genotype. Keywords: HIV therapy; mathematical modelling; treatment; genotype

  16. A therapeutic HIV vaccine using coxsackie-HIV recombinants: a possible new strategy.

    Science.gov (United States)

    Halim, S S; Collins, D N; Ramsingh, A I

    2000-10-10

    The ultimate goal in the treatment of HIV-infected persons is to prevent disease progression. A strategy to accomplish this goal is to use chemotherapy to reduce viral load followed by immunotherapy to stimulate HIV-specific immune responses that are observed in long-term asymptomatic individuals. An effective, live, recombinant virus, expressing HIV sequences, would be capable of inducing both CTL and CD4(+) helper T cell responses. To accomplish these goals, the viral vector must be immunogenic yet retain its avirulent phenotype in a T cell-deficient host. We have identified a coxsackievirus variant, CB4-P, that can induce protective immunity against a virulent variant. In addition, the CB4-P variant remains avirulent in mice lacking CD4(+) helper T cells, suggesting that CB4-P may be uniquely suited as a viral vector for a therapeutic HIV vaccine. Two strategies designed to elicit CTL and CD4(+) helper T cell responses were used to construct CB4-P/HIV recombinants. Recombinant viruses were viable, genetically stable, and retained the avirulent phenotype of the parental virus. In designing a viral vector for vaccine development, an issue that must be addressed is whether preexisting immunity to the vector would affect subsequent administration of the recombinant virus. Using a test recombinant, we showed that prior exposure to the parental CB4-P virus did not affect the ability of the recombinant to induce a CD4(+) T cell response against the foreign sequence. The results suggest that a "cocktail" of coxsackie/HIV recombinants may be useful as a therapeutic HIV vaccine.

  17. Utility of urine lipoarabinomannan (LAM) in diagnosing tuberculosis and predicting mortality with and without HIV: prospective TB cohort from the Thailand Big City TB Research Network.

    Science.gov (United States)

    Suwanpimolkul, Gompol; Kawkitinarong, Kamon; Manosuthi, Weerawat; Sophonphan, Jiratchaya; Gatechompol, Sivaporn; Ohata, Pirapon June; Ubolyam, Sasiwimol; Iampornsin, Thatri; Katerattanakul, Pairaj; Avihingsanon, Anchalee; Ruxrungtham, Kiat

    2017-06-01

    To evaluate the applicability and accuracy of the urine lipoarabinomannan (LAM) test in tuberculosis (TB)/HIV co-infected patients and HIV-negative patients with disseminated TB. Frozen urine samples obtained at baseline from patients in the TB research cohort with proven culture-positive TB were selected for blinded urine LAM testing. One hundred and nine patients were categorized into four groups: (1) HIV-positive patients with TB; (2) HIV-negative patients with disseminated TB; (3) HIV-negative immunocompromised patients with TB; and (4) patients with diseases other than TB. The sensitivity of urine LAM testing for culture-positive TB, specificity of urine LAM testing for patients without TB, positive predictive value (PPV), and negative predictive value (NPV) were assessed. The sensitivity of the urine LAM test in group 1 patients with a CD4 T-cell count of >100, ≤100, and ≤50 cells/mm 3 was 38.5%, 40.6%, and 45%, respectively. The specificity and PPV of the urine LAM test were >80%. The sensitivity of the test was 20% in group 2 and 12.5% in group 3, and the specificity and PPV were 100% for both groups. A positive urine LAM test result was significantly associated with death. This promising diagnostic tool could increase the yield of TB diagnosis and may predict the mortality rate of TB infection, particularly in TB/HIV co-infected patients. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

  18. A pharmacogenetic study of CD4 recovery in response to HIV antiretroviral therapy in two South African population groups.

    Science.gov (United States)

    Parathyras, John; Gebhardt, Stefan; Hillermann-Rebello, Renate; Grobbelaar, Nelis; Venter, Mauritz; Warnich, Louise

    2009-05-01

    South Africa, like many other Southern African countries, has one of the highest HIV infection rates in the world and many individuals consequently receive antiretroviral therapy (ART). However, knowledge regarding (i) the prevalence of functional single nucleotide polymorphisms (SNPs) in pharmacologically relevant genes, and (ii) variance in pharmacotherapy both within and between different populations and ethnic groups is limited. The aim of this study was to determine whether selected polymorphisms in cytochrome P450 (CYP) genes (CYP2B6 and CYP3A4) and the multidrug-resistance 1 (ABCB1) gene underlie altered antiretroviral (ARV) drug response in two South African populations. DNA samples from 182 HIV-positive individuals of Mixed-Ancestry and Xhosa ethnicity on ART were genotyped for the A-392G SNP in CYP3A4, the G516T and A785G SNPs in CYP2B6, and the T-129C, C1236T, G2677T/A and C3435T SNPs in ABCB1. Univariate two-way analysis of variance (ANOVA) testing revealed no apparent effect of ethnicity on immune recovery (in terms of CD4-cell count) in response to ART. Univariate one-way ANOVA testing revealed a discernible effect of genotype on immune recovery in the cases of the T-129C (P=0.03) and G2677A (P<0.01) polymorphisms in the ABCB1 gene. This study serves as a basis for better understanding and possible prediction of pharmacogenetic risk profiles and drug response in individuals and ethnic groups in South Africa.

  19. Depression and anxiety mediate perceived social support to predict health-related quality of life in pregnant women living with HIV.

    Science.gov (United States)

    Xiaowen, Wang; Guangping, Guo; Ling, Zhou; Jiarui, Zheng; Xiumin, Liang; Zhaoqin, Li; Hongzhuan, Luo; Yuyan, Yang; Liyuan, Yang; Lin, Lu

    2018-04-01

    Pregnant women living with HIV represent one of the most high-priority groups for HIV treatment and health assessment. Although social support has been shown to be a protective factor for improved health-related quality of life (HRQoL), and depression and anxiety have been identified as two major causes of psychological distress among people living with HIV, it is still unclear how social support, anxiety, and depression interact to influence HRQoL. The objective of our study was to demonstrate the nature of predictors, direct effects and mediator effects among social support, anxiety, depression symptoms and HRQoL in pregnant women living with HIV. We investigated a total of 101 pregnant women living with HIV in Yunnan province in China from April 2016 to June 2016. All participants completed the Social Support Rating Scale (SSRS), the Chinese version of the Hospital Anxiety and Depression Scales (HADS) and Quality of Life instruments (EuroQoL Five Dimensions Questionnaire, EQ-5D). The relationships between the variables were examined by Pearson's or Spearman's correlation analysis. Predictor effects were tested using separate multiple regressions, controlling for demographic variables and HIV diagnosis variables. Direct and mediation effects of social support on HRQoL were tested using a structural equation model (SEM). Anxiety and depression symptoms were negatively correlated with subjective social support, support utilization, social support and HRQoL. Social support significantly predicted better HRQoL, and anxiety and depression symptoms significantly predicted poorer HRQoL. Anxiety and depression symptoms partially mediated the associations between social support and HRQoL. Anxiety and depression symptoms completely mediated the associations of objective support and support utilization with HRQoL. Interventions to improve HRQoL in pregnant women living with HIV must consider the mediation effect of anxiety and depression symptoms on the association between

  20. The private sector role in HIV/AIDS in the context of an expanded global response: expenditure trends in five sub-Saharan African countries.

    Science.gov (United States)

    Sulzbach, Sara; De, Susna; Wang, Wenjuan

    2011-07-01

    Global financing for the HIV response has reached unprecedented levels in recent years. Over US$10 billion were mobilized in 2007, an effort credited with saving the lives of millions of people living with HIV (PLHIV). A relatively unexamined aspect of the global HIV response is the role of the private sector in financing HIV/AIDS services. As the nature of the response evolves from emergency relief to long-term sustainability, understanding current and potential contributions from the private sector is critical. This paper examines trends in private sector financing, management and resource consumption related to HIV/AIDS in five sub-Saharan African countries, with a particular emphasis on the effects of recently scaled-up donor funding on private sector contributions. We analysed National Health Accounts HIV/AIDS subaccount data for Kenya, Malawi, Rwanda, Tanzania and Zambia between 2002 and 2006. HIV subaccounts provide comparable data on the flow of HIV/AIDS funding from source to use. Findings indicate that private sector contributions decreased in all countries except Tanzania. With regards to managing HIV/AIDS funds, non-governmental organizations are increasingly controlling the largest share of resources relative to other stakeholders, whereas private for-profit entities are managing fewer HIV/AIDS resources since the donor influx. The majority of HIV/AIDS funds were spent in the public sector, although a considerable amount was spent at private facilities, largely fuelled by out-of-pocket (OOP) payments. On the whole, OOP spending by PLHIV decreased over the 4-year period, with the exception of Malawi, demonstrating that PLHIV have increased access to free or subsidized HIV/AIDS services. Our findings suggest that the influx of donor funding has led to decreased private contributions for HIV/AIDS. The reduction in private sector investment and engagement raises concerns about the sustainability of HIV/AIDS programmes over the long term, particularly in

  1. An improved protocol for efficient engraftment in NOD/LTSZ-SCIDIL-2Rγnull mice allows HIV replication and development of anti-HIV immune responses.

    Directory of Open Access Journals (Sweden)

    Maneesh Singh

    Full Text Available Cord blood hematopoietic progenitor cells (CB-HPCs transplanted immunodeficient NOD/LtsZ-scidIL2Rγ(null (NSG and NOD/SCID/IL2Rγ(null (NOG mice need efficient human cell engraftment for long-term HIV-1 replication studies. Total body irradiation (TBI is a classical myeloablation regimen used to improve engraftment levels of human cells in these humanized mice. Some recent reports suggest the use of busulfan as a myeloablation regimen to transplant HPCs in neonatal and adult NSG mice. In the present study, we further ameliorated the busulfan myeloablation regimen with fresh CB-CD34+cell transplantation in 3-4 week old NSG mice. In this CB-CD34+transplanted NSG mice engraftment efficiency of human CD45+cell is over 90% in peripheral blood. Optimal engraftment promoted early and increased CD3+T cell levels, with better lymphoid tissue development and prolonged human cell chimerism over 300 days. These humanized NSG mice have shown long-lasting viremia after HIV-1JRCSF and HIV-1Bal inoculation through intravenous and rectal routes. We also saw a gradual decline of the CD4+T cell count, widespread immune activation, up-regulation of inflammation marker and microbial translocation after HIV-1 infection. Humanized NSG mice reconstituted according to our new protocol produced, moderate cellular and humoral immune responses to HIV-1 postinfection. We believe that NSG mice reconstituted according to our easy to use protocol will provide a better in vivo model for HIV-1 replication and anti-HIV-1 therapy trials.

  2. Incorporation of chimeric HIV-SIV-Env and modified HIV-Env proteins into HIV pseudovirions

    International Nuclear Information System (INIS)

    Devitt, Gerard; Emerson, Vanessa; Holtkotte, Denise; Pfeiffer, Tanya; Pisch, Thorsten; Bosch, Valerie

    2007-01-01

    Low level incorporation of the viral glycoprotein (Env) into human immunodeficiency virus (HIV) particles is a major drawback for vaccine strategies against HIV/AIDS in which HIV particles are used as immunogen. Within this study, we have examined two strategies aimed at achieving higher levels of Env incorporation into non-infectious pseudovirions (PVs). First, we have generated chimeric HIV/SIV Env proteins containing the truncated C-terminal tail region of simian immunodeficiency virus (SIV)mac239-Env767 stop , which mediates strongly increased incorporation of SIV-Env into SIV particles. In a second strategy, we have employed a truncated HIV-Env protein (Env-Tr752 N750K ) which we have previously demonstrated to be incorporated into HIV virions, generated in infected T-cells, to a higher level than that of Wt-HIV-Env. Although the chimeric HIV/SIV Env proteins were expressed at the cell surface and induced increased levels of cell-cell fusion in comparison to Wt-HIV-Env, they did not exhibit increased incorporation into either HIV-PVs or SIV-PVs. Only Env-Tr752 N750K exhibited significantly higher (threefold) levels of incorporation into HIV-PVs, an improvement, which, although not dramatic, is worthwhile for the large-scale preparation of non-infectious PVs for vaccine studies aimed at inducing Env humoral responses

  3. Understanding HIV infection for the design of a therapeutic vaccine. Part I: Epidemiology and pathogenesis of HIV infection.

    Science.gov (United States)

    de Goede, A L; Vulto, A G; Osterhaus, A D M E; Gruters, R A

    2015-03-01

    HIV infection leads to a gradual loss CD4+ T lymphocytes comprising immune competence and progression to AIDS. Effective treatment with combined antiretroviral drugs (cART) decreases viral load below detectable levels but is not able to eliminate the virus from the body. The success of cART is frustrated by the requirement of expensive life-long adherence, accumulating drug toxicities and chronic immune activation resulting in increased risk of several non-AIDS disorders, even when viral replication is suppressed. Therefore there is a strong need for therapeutic strategies as an alternative to cART. Immunotherapy, or therapeutic vaccination, aims to increase existing immune responses against HIV or induce de novo immune responses. These immune responses should provide a functional cure by controlling viral replication and preventing disease progression in the absence of cART. The key difficulty in the development of an HIV vaccine is our ignorance of the immune responses that control of viral replication, and thus how these responses can be elicited and how they can be monitored. Part one of this review provides an extensive overview of the (patho-) physiology of HIV infection. It describes the structure and replication cycle of HIV, the epidemiology and pathogenesis of HIV infection and the innate and adaptive immune responses against HIV. Part two of this review discusses therapeutic options for HIV. Prevention modalities and antiretroviral therapy are briefly touched upon, after which an extensive overview on vaccination strategies for HIV is provided, including the choice of immunogens and delivery strategies. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  4. Impact of a new vaccine clinic on hepatitis B vaccine completion and immunological response rates in an HIV-positive cohort.

    Science.gov (United States)

    Rock, Clare; de Barra, Eoghan; Sadlier, Corinna; Kelly, Sinead; Dowling, Catherine; McNally, Cora; Bergin, Colm

    2013-06-01

    Hepatitis B virus vaccination (HBVV) in the HIV-infected population has poor reported completion rates and immunological response rates. At our HIV clinic, we established a vaccine clinic to improve HBVV outcomes using interventions such as SMS text reminders and double-dose (DD) HBVV for standard-dose non-responders (SD NRs). A five-year (2003-2008) retrospective review of the completion rates and immunological response rates for HBVV after the establishment of the dedicated vaccine clinic was conducted. Statistical significance was assumed at presponse rate to DD HBVV among SD NRs. On-treatment analysis showed an 88% (155/176) overall immunological response to SD HBVV and DD HBVV, if required. High HBVV completion and response rates in this HIV cohort were enabled through the use of multiple interventions, including the use of SMS text message reminders and routine referral for DD vaccination. Copyright © 2012 King Saud Bin Abdulaziz University for Health Sciences. Published by Elsevier Ltd. All rights reserved.

  5. Prediction of treatment response to adalimumab

    DEFF Research Database (Denmark)

    Krintel, S B; Dehlendorff, C; Hetland, M L

    2016-01-01

    At least 30% of patients with rheumatoid arthritis (RA) do not respond to biologic agents, which emphasizes the need of predictive biomarkers. We aimed to identify microRNAs (miRNAs) predictive of response to adalimumab in 180 treatment-naïve RA patients enrolled in the OPtimized treatment algori...... of low expression of miR-22 and high expression of miR-886.3p was associated with EULAR good response. Future studies to assess the utility of these miRNAs as predictive biomarkers are needed.The Pharmacogenomics Journal advance online publication, 5 May 2015; doi:10.1038/tpj.2015.30....

  6. APOBEC3G inhibits HIV-1 RNA elongation by inactivating the viral trans-activation response element.

    Science.gov (United States)

    Nowarski, Roni; Prabhu, Ponnandy; Kenig, Edan; Smith, Yoav; Britan-Rosich, Elena; Kotler, Moshe

    2014-07-29

    Deamination of cytidine residues in viral DNA is a major mechanism by which APOBEC3G (A3G) inhibits vif-deficient human immunodeficiency virus type 1 (HIV-1) replication. dC-to-dU transition following RNase-H activity leads to viral cDNA degradation, production of non-functional proteins, formation of undesired stop codons and decreased viral protein synthesis. Here, we demonstrate that A3G provides an additional layer of defense against HIV-1 infection dependent on inhibition of proviral transcription. HIV-1 transcription elongation is regulated by the trans-activation response (TAR) element, a short stem-loop RNA structure required for elongation factors binding. Vif-deficient HIV-1-infected cells accumulate short viral transcripts and produce lower amounts of full-length HIV-1 transcripts due to A3G deamination of the TAR apical loop cytidine, highlighting the requirement for TAR loop integrity in HIV-1 transcription. We further show that free single-stranded DNA (ssDNA) termini are not essential for A3G activity and a gap of CCC motif blocked with juxtaposed DNA or RNA on either or 3'+5' ends is sufficient for A3G deamination. These results identify A3G as an efficient mutator and that deamination of (-)SSDNA results in an early block of HIV-1 transcription. Copyright © 2014 Elsevier Ltd. All rights reserved.

  7. A decade of an HIV workplace programme in armed conflict zones; a social responsibility response of the International Committee of the Red Cross.

    Science.gov (United States)

    Du Mortier, Stéphane; Mukangu, Silas; Sagna, Charles; Nyffenegger, Laurent; Aebischer Perone, Sigiriya

    2016-01-01

    The International Committee of the Red Cross (ICRC) works in fragile States and in armed conflict zones. Some of them are affected by the HIV pandemic. Within the framework of its social responsibility programme concerning HIV affecting its staff members, the organization has implemented an HIV workplace programme since 2004. We carried out a retrospective analysis over 10 years. Data collected were initially essentially qualitative and process-oriented, but were complemented over the years by data on annual voluntary counselling and testing (VCT) uptake and on direct annual costs covering awareness, testing and antiretroviral therapy. The number of people covered by the programme grew from none in 2003 to 4,438 in 2015, with an increase in annual VCT uptake over the years increasing from 376 persons (14 %) in 2007 to 2,663 in 2015 (60 %). Over the years, the services were expanded from awareness raising to bringing VCT to the workplace, as well as offering testing and health coverage of other conditions and innovative approaches to facing challenges linked to situations of violence. Within its social responsibility framework, the ICRC has shown the importance and feasibility of a workplace HIV programme in conflict zones. A sustainable workplace programme in these conflict settings requires constant adaptation, with regular follow-up given the relatively high turnover of staff, and ensuring sustainable stocks of condoms and antiretroviral drugs.

  8. Reorienting the HIV response in Niger toward sex work interventions: from better evidence to targeted and expanded practice.

    Science.gov (United States)

    Fraser, Nicole; Kerr, Cliff C; Harouna, Zakou; Alhousseini, Zeinabou; Cheikh, Nejma; Gray, Richard; Shattock, Andrew; Wilson, David P; Haacker, Markus; Shubber, Zara; Masaki, Emiko; Karamoko, Djibrilla; Görgens, Marelize

    2015-03-01

    Niger's low-burden, sex-work-driven HIV epidemic is situated in a context of high economic and demographic growth. Resource availability of HIV/AIDS has been decreasing recently. In 2007-2012, only 1% of HIV expenditure was for sex work interventions, but an estimated 37% of HIV incidence was directly linked to sex work in 2012. The Government of Niger requested assistance to determine an efficient allocation of its HIV resources and to strengthen HIV programming for sex workers. Optima, an integrated epidemiologic and optimization tool, was applied using local HIV epidemic, demographic, programmatic, expenditure, and cost data. A mathematical optimization algorithm was used to determine the best resource allocation for minimizing HIV incidence and disability-adjusted life years (DALYs) over 10 years. Efficient allocation of the available HIV resources, to minimize incidence and DALYs, would increase expenditure for sex work interventions from 1% to 4%-5%, almost double expenditure for antiretroviral treatment and for the prevention of mother-to-child transmission, and reduce expenditure for HIV programs focusing on the general population. Such an investment could prevent an additional 12% of new infections despite a budget of less than half of the 2012 reference year. Most averted infections would arise from increased funding for sex work interventions. This allocative efficiency analysis makes the case for increased investment in sex work interventions to minimize future HIV incidence and DALYs. Optimal HIV resource allocation combined with improved program implementation could have even greater HIV impact. Technical assistance is being provided to make the money invested in sex work programs work better and help Niger to achieve a cost-effective and sustainable HIV response.

  9. Evaluation of four rapid tests for diagnosis and differentiation of HIV-1 and HIV-2 infections in Guinea-Conakry, West Africa.

    Science.gov (United States)

    Chaillet, Pascale; Tayler-Smith, Katie; Zachariah, Rony; Duclos, Nanfack; Moctar, Diallo; Beelaert, Greet; Fransen, Katrien

    2010-09-01

    With both HIV-1 and HV-2 prevalent in Guinea-Conakry, accurate diagnosis and differentiation is crucial for treatment purposes. Thus, four rapid HIV tests were evaluated for their HIV-1 and HIV-2 diagnostic and discriminative capacity for use in Guinea-Conakry. These included SD Bioline HIV 1/2 3.0 (Standard Diagnostics Inc.), Genie II HIV1/HIV2 (Bio-Rad), First Response HIV Card Test 1-2.0 (PMC Medical) and Immunoflow HIV1-HIV2 (Core Diagnostics). Results were compared with gold standard tests (INNO-LIA HIV-I/II Score) and NEW LAV BLOT II (Bio-Rad). Four hundred and forty three sequential stored HIV-positive serum samples, of known HIV-type, were evaluated. Genie II HIV1/HIV2, Immunoflow HIV1-HIV2 and SD Bioline HIV 1/2 3.0 had 100% sensitivity (95% CI, 98.9-100%) while for First Response HIV Card Test 1-2.0 this was 99.5% (95% CI, 98.2%-99.9%). In terms of discriminatory capacity, Genie II HIV1/HIV2 identified 382/ 384(99.5%) HIV-1 samples, 49/ 52(95%) HIV-2 and 7/7(100%) HIV-positive untypable samples. Immunoflow HIV1-HIV2 identified 99% HIV-1, 67% HIV-2 and all HIV-positive untypable samples. First Response HIV Card Test 1-2.0 identified 94% HIV-1, 64% HIV-2 and 57% HIV-positive untypable samples. SD-Bioline HIV 1/2 3.0 was the worst overall performer identifying 65% HIV-1, 69% HIV-2 and all HIV-positive untypable samples. The use of SD Bioline HIV 1/2 3.0 (the current standard in Guinea-Conakry) as a discriminatory HIV test is poor and may be best replaced by Immunoflow HIV1-HIV2. Copyright 2010 Royal Society of Tropical Medicine and Hygiene. Published by Elsevier Ltd. All rights reserved.

  10. Heroin use is associated with suppressed pro-inflammatory cytokine response after LPS exposure in HIV-infected individuals.

    Directory of Open Access Journals (Sweden)

    Hinta Meijerink

    Full Text Available Opioid use is associated with increased incidence of infectious diseases. Although experimental studies have shown that opioids affect various functions of immune cells, only limited data are available from human studies. Drug use is an important risk factor for HIV transmission; however no data are available whether heroin and/or methadone modulate immune response. Therefore, we examined the effect of heroin and methadone use among HIV-infected individuals on the production of cytokines after ex vivo stimulation with various pathogens.Treatment naïve HIV-infected individuals from Indonesia were recruited. Several cohorts of individuals were recruited: 1 using heroin 2 receiving methadone opioid substitution 3 using heroin over 1 year ago and 4 controls (never used opioids. Whole blood was stimulated with Mycobacterium tuberculosis, Candida albicans and LPS for 24 to 48 hours. Cytokine production (IL-1 β, IL-6, IL-10, IFN-α, IFN-γ and TNF-α was determined using multiplex beads assay.Among 82 individuals, the cytokine levels in unstimulated samples did not differ between groups. Overall, heroin users had significantly lower cytokine response after exposure to LPS (p<0.05. After stimulation with either M. tuberculosis or C. albicans the cytokine production of all groups were comparable.The cytokine production after exposure to LPS is significantly down-regulated in HIV-infected heroin users. Interesting, methadone use did not suppress cytokine response, which could have implications guidelines of opioid substitution.

  11. Nosocomial infections in HIV-infected and HIV-uninfected children ...

    African Journals Online (AJOL)

    The interaction between tuberculosis and HIV-infected infection is well known and is responsible for the increase in the incidence of tuberculosis ... This retrospective case-control study evaluated the occurrence of nosocomial infections in (HIV)-infected children and age- and time of ... complicated disease, or whose social.

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

    Science.gov (United States)

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

    2001-12-01

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

  13. Stigma, an important source of dissatisfaction of health workers in HIV response in Vietnam: a qualitative study.

    Science.gov (United States)

    Pham, Ha Nguyen; Protsiv, Myroslava; Larsson, Mattias; Ho, Hien Thi; de Vries, Daniel H; Thorson, Anna

    2012-12-21

    Like in many other low- and middle-income countries, the recent development of an HIV epidemic in Vietnam has led to a growing need for prevention, treatment, care, and support services for people living with HIV (PLHIV). This puts greater demands on the national HIV services, primarily on health workers, which increases the importance of their job satisfaction and working conditions. This study describes health worker perceptions and explores the factors that influence job satisfaction and dissatisfaction of health personnel working on the HIV response in Vietnam. Spector's job satisfaction model was used as the theoretical framework for the study design and analysis. The study employed a qualitative design with 7 focus group discussions and 15 semi-structured interviews with health workers, purposively selected from national and provincial organizations responsible for HIV services in 5 cities and provinces in Vietnam. Data were analyzed using a hybrid approach of theory-driven and data-driven coding and theme development using qualitative analysis software. HIV services are perceived by Vietnamese health workers as having both positive and negative aspects. Factors related to job satisfaction included training opportunities, social recognition, and meaningful tasks. Factors related to job dissatisfaction included unsatisfactory compensation, lack of positive feedback and support from supervisors, work-related stress from a heavy workload, fear of infection, and HIV-related stigma because of association with PLHIV. An adjusted Spector's model of job satisfaction for HIV service health workers was developed from these results. This study confirmed the relationship between stigmatization of PLHIV and stigma experienced by staff because of association with PLHIV from families, colleagues, and society. The experiencing stigma results in additional work-related stress, low self-esteem, poor views of their profession, and lower income. The study shows the importance of

  14. Stigma, an important source of dissatisfaction of health workers in HIV response in Vietnam: a qualitative study

    Directory of Open Access Journals (Sweden)

    Pham Ha Nguyen

    2012-12-01

    Full Text Available Abstract Background Like in many other low- and middle-income countries, the recent development of an HIV epidemic in Vietnam has led to a growing need for prevention, treatment, care, and support services for people living with HIV (PLHIV. This puts greater demands on the national HIV services, primarily on health workers, which increases the importance of their job satisfaction and working conditions. This study describes health worker perceptions and explores the factors that influence job satisfaction and dissatisfaction of health personnel working on the HIV response in Vietnam. Spector’s job satisfaction model was used as the theoretical framework for the study design and analysis. Methods The study employed a qualitative design with 7 focus group discussions and 15 semi-structured interviews with health workers, purposively selected from national and provincial organizations responsible for HIV services in 5 cities and provinces in Vietnam. Data were analyzed using a hybrid approach of theory-driven and data-driven coding and theme development using qualitative analysis software. Results HIV services are perceived by Vietnamese health workers as having both positive and negative aspects. Factors related to job satisfaction included training opportunities, social recognition, and meaningful tasks. Factors related to job dissatisfaction included unsatisfactory compensation, lack of positive feedback and support from supervisors, work-related stress from a heavy workload, fear of infection, and HIV-related stigma because of association with PLHIV. An adjusted Spector’s model of job satisfaction for HIV service health workers was developed from these results. Conclusion This study confirmed the relationship between stigmatization of PLHIV and stigma experienced by staff because of association with PLHIV from families, colleagues, and society. The experiencing stigma results in additional work-related stress, low self-esteem, poor views of

  15. Human Rights in the Fourth Decade of the HIV/AIDS Response: An Inspiring Legacy and Urgent Imperative.

    Science.gov (United States)

    Enoch, Jamie; Piot, Peter

    2017-12-01

    More than 35 years since the HIV/AIDS pandemic began, HIV continues to cause almost two million new infections each year, and the "end of AIDS" by 2030 remains elusive. 1 Violations of human rights continue to fuel high rates of new infections among key populations and a generalized epidemic in much of sub-Saharan Africa. Meanwhile, as political shifts worldwide threaten not only HIV funding but also progress toward the globalization of human rights, civil society mobilization and advocacy founded firmly on human rights principles have a more vital role to play than ever. Encouragingly, there are numerous examples of successful integration of human rights-based approaches into HIV prevention and treatment initiatives, and evidence increasingly demonstrates that norms enshrining the respect, protection, and fulfillment of human rights can translate into improved public health. 2 This essay will succinctly trace the historic emergence of human rights as an issue at the heart of the HIV/AIDS response; it will then provide examples of progress and setbacks in recent years and consider the potential for rights promotion to address the structural drivers of HIV. Finally, it will consider how the primacy of human rights in HIV/AIDS has affected other fields of global health and will highlight the continuing imperative to work with civil society to protect and promote human rights to reduce the burden of HIV/AIDS.

  16. Being and Becoming “Fully Human” in an Hiv-Positive World: Hiv ...

    African Journals Online (AJOL)

    Feminists have researched the link between gender and HIV/AIDS and shown that women are not always morally responsible for being HIV-positive. This article contributes to the debate by presenting a systematic discussion of women's experience of HIV/AIDS and spirituality. It offers a model of full humanity that interprets ...

  17. Priming B cell-mediated anti-HIV envelope responses by vaccination allows for the long-term control of infection in macaques exposed to a R5-tropic SHIV

    International Nuclear Information System (INIS)

    Buckner, Clarisa; Gines, Leoned G.; Saunders, Cheryl J.; Vojtech, Lucia; Srivastava, Indresh; Gettie, Agegnehu; Bohm, Rudolph; Blanchard, James; Barnett, Susan W.; Safrit, Jeffrey T.; Stamatatos, Leonidas

    2004-01-01

    The potential of vaccine-elicited anti-HIV envelope antibodies to control HIV-infection was evaluated by immunizing macaques with the HIV envelope protein and transiently depleting them of their CD8+ cells before intravenous challenge with the pathogenic CCR5-tropic SIV/HIV chimeric virus, SHIV SF162P4 . Although sterilizing immunity was not achieved, all vaccinated animals effectively controlled infection and remained free of disease for the duration of observation (over 3 years). In contrast, during the same period, the control animals progressed to disease. Both the vaccinees and the controls developed robust cell-mediated antiviral and neutralizing antibody responses following infection. A comparative analysis of these responses suggests that the more effective long-term control of infection by the vaccinated animals is due to the more rapid development of anti-HIV envelope antibodies. These studies suggest that priming by vaccination of B cell anti-HIV envelope responses maybe crucial for the long-term control of HIV infection

  18. HIV exposed seronegative (HESN compared to HIV infected individuals have higher frequencies of telomeric Killer Immunoglobulin-like Receptor (KIR B motifs; Contribution of KIR B motif encoded genes to NK cell responsiveness.

    Directory of Open Access Journals (Sweden)

    Elise Jackson

    Full Text Available Previously, we showed that Killer Immunoglobulin-like Receptor (KIR3DS1 homozygotes (hmz are more frequent in HIV exposed seronegative (HESN than in recently HIV infected (HIV+ individuals. KIR3DS1 encodes an activating Natural Killer (NK cell receptor (NKR. The link between KIR genotype and HIV outcomes likely arises from the function that NK cells acquire through expression of particular NKRs. An initial screen of 97 HESN and 123 HIV+ subjects for the frequency of KIR region gene carriage observed between-group differences for several telomeric KIR region loci. In a larger set of up to 106 HESN and 439 HIV+ individuals, more HESN than HIV+ subjects were KIR3DS1 homozygotes, lacked a full length KIR2DS4 gene and carried the telomeric group B KIR haplotype motif, TB01. TB01 is characterized by the presence of KIR3DS1, KIR2DL5A, KIR2DS3/5 and KIR2DS1, in linkage disequilibrium with each other. We assessed which of the TB01 encoded KIR gene products contributed to NK cell responsiveness by stimulating NK cells from 8 HIV seronegative KIR3DS1 and TB01 motif homozygotes with 721.221 HLA null cells and evaluating the frequency of KIR3DS1+/-KIR2DL5+/-, KIR3DS1+/-KIR2DS1+/-, KIR3DS1+/-KIR2DS5+/- NK cells secreting IFN-γ and/or expressing CD107a. A higher frequency of NK cells expressing, versus not, KIR3DS1 responded to 721.221 stimulation. KIR2DL5A+, KIR2DS1+ and KIR2DS5+ NK cells did not contribute to 721.221 responses or modulate those by KIR3DS1+ NK cells. Thus, of the TB01 KIR gene products, only KIR3DS1 conferred responsiveness to HLA-null stimulation, demonstrating its ligation can activate ex vivo NK cells.

  19. Using protection motivation theory to predict condom usage and assess HIV health communication efficacy in Singapore.

    Science.gov (United States)

    Lwin, May O; Stanaland, Andrea J S; Chan, Desmond

    2010-01-01

    The number of individuals infected with HIV/AIDS continues to rise in Asia. Condom use is considered to be the first line of defense against AIDS (UNAIDS, 2006). Using protection motivation theory (Rogers, 1983), this research aims to first understand the factors affecting condom usage intention among homosexual and heterosexual men in Singapore, and then to utilize those findings to assess the efficacy of HIV-directed health communications. We collected survey data from 484 men and analyzed the data using hierarchical regression and structural equation modeling. We found self-efficacy to be a significant predictor for both groups of men, together with perceived severity for homosexuals and response efficacy for heterosexuals. Next, we analyzed HIV-directed condom usage communication materials and found that the use of threat appeal themes is more common than themes promoting self-efficacy. Implications for health communications and policy are discussed.

  20. Gene expression profiling of the host response to HIV-1 B, C, or A/E infection in monocyte-derived dendritic cells

    International Nuclear Information System (INIS)

    Solis, Mayra; Wilkinson, Peter; Romieu, Raphaelle; Hernandez, Eduardo; Wainberg, Mark A.; Hiscott, John

    2006-01-01

    Dendritic cells (DC) are among the first targets of human immunodeficiency virus type-1 (HIV-1) infection and in turn play a crucial role in viral transmission to T cells and in the regulation of the immune response. The major group of HIV-1 has diversified genetically based on variation in env sequences and comprise at least 11 subtypes. Because little is known about the host response elicited against different HIV-1 clade isolates in vivo, we sought to use gene expression profiling to identify genes regulated by HIV-1 subtypes B, C, and A/E upon de novo infection of primary immature monocyte-derived DC (iMDDCs). A total of 3700 immune-related genes were subjected to a significance analysis of microarrays (SAM); 656 genes were selected as significant and were further divided into 8 functional categories. Regardless of the time of infection, 20% of the genes affected by HIV-1 were involved in signal transduction, followed by 14% of the genes identified as transcription-related genes, and 7% were classified as playing a role in cell proliferation and cell cycle. Furthermore, 7% of the genes were immune response genes. By 72 h postinfection, genes upregulated by subtype B included the inhibitor of the matrix metalloproteinase TIMP2 and the heat shock protein 40 homolog (Hsp40) DNAJB1, whereas the IFN inducible gene STAT1, the MAPK1/ERK2 kinase regulator ST5, and the chemokine CXCL3 and SHC1 genes were induced by subtypes C and A/E. These analyses distinguish a temporally regulated host response to de novo HIV-1 infection in primary dendritic cells

  1. Immunosenescent CD57+CD4+ T-cells Accumulate and Contribute to Interferon-γ Responses in HIV Patients Responding Stably to ART

    Directory of Open Access Journals (Sweden)

    Sonia Fernandez

    2011-01-01

    Full Text Available HIV-infected individuals responding to antiretroviral therapy (ART after severe CD4+ T-cell depletion may retain low responses to recall antigens [eg: cytomegalovirus (CMV] and altered expression of T-cell co-stimulatory molecules consistent with immunosenescence. We investigated the capacity of phenotypically senescent cells to generate cytokines in HIV patients receiving long-term ART (n = 18 and in healthy controls (n = 10. Memory T-cells were assessed by interferon (IFN-γ ELISpot assay and flow cytometrically via IFN-γ or IL-2. Proportions of CD57brightCD28null CD4+ T-cells correlated with IFN-γ responses to CMV (p = 0.009 and anti-CD3 (p = 0.002 in HIV patients only. Proportions of CD57brightCD28null CD8+ T-cells and CD8+ T-cell IFN-γ responses to CMV peptides correlated in controls but not HIV patients. IL-2 was predominantly produced by CD28+T-cells from all donors, whereas IFN-γ was mostly produced by CD57+ T-cells. The findings provide evidence of an accumulation of immunosenescent T-cells able to make IFN-γ. This may influence the pathogenesis of secondary viral infections in HIV patients receiving ART.

  2. Response to intravenous fentanyl infusion predicts subsequent response to transdermal fentanyl.

    Science.gov (United States)

    Hayashi, Norihito; Kanai, Akifumi; Suzuki, Asaha; Nagahara, Yuki; Okamoto, Hirotsugu

    2016-04-01

    Prediction of the response to transdermal fentanyl (FENtd) before its use for chronic pain is desirable. We tested the hypothesis that the response to intravenous fentanyl infusion (FENiv) can predict the response to FENtd, including the analgesic and adverse effects. The study subjects were 70 consecutive patients with chronic pain. The response to fentanyl at 0.1 mg diluted in 50 ml of physiological saline and infused over 30 min was tested. This was followed by treatment with FENtd (Durotep MT patch 2.1 mg) at a dose of 12.5 µg/h for 2 weeks. Pain intensity before and after FENiv and 2 weeks after FENtd, and the response to treatment, were assessed by the numerical rating scale (NRS), clinical global impression-improvement scale (CGI-I), satisfaction scale (SS), and adverse effects. The NRS score decreased significantly from 7 (4-9) [median (range)] at baseline to 3 (0-8) after FENiv (p 0.04, each). The analgesic and side effects after intravenous fentanyl infusion can be used to predict the response to short-term transdermal treatment with fentanyl.

  3. A model for predicting lung cancer response to therapy

    International Nuclear Information System (INIS)

    Seibert, Rebecca M.; Ramsey, Chester R.; Hines, J. Wesley; Kupelian, Patrick A.; Langen, Katja M.; Meeks, Sanford L.; Scaperoth, Daniel D.

    2007-01-01

    Purpose: Volumetric computed tomography (CT) images acquired by image-guided radiation therapy (IGRT) systems can be used to measure tumor response over the course of treatment. Predictive adaptive therapy is a novel treatment technique that uses volumetric IGRT data to actively predict the future tumor response to therapy during the first few weeks of IGRT treatment. The goal of this study was to develop and test a model for predicting lung tumor response during IGRT treatment using serial megavoltage CT (MVCT). Methods and Materials: Tumor responses were measured for 20 lung cancer lesions in 17 patients that were imaged and treated with helical tomotherapy with doses ranging from 2.0 to 2.5 Gy per fraction. Five patients were treated with concurrent chemotherapy, and 1 patient was treated with neoadjuvant chemotherapy. Tumor response to treatment was retrospectively measured by contouring 480 serial MVCT images acquired before treatment. A nonparametric, memory-based locally weight regression (LWR) model was developed for predicting tumor response using the retrospective tumor response data. This model predicts future tumor volumes and the associated confidence intervals based on limited observations during the first 2 weeks of treatment. The predictive accuracy of the model was tested using a leave-one-out cross-validation technique with the measured tumor responses. Results: The predictive algorithm was used to compare predicted verse-measured tumor volume response for all 20 lesions. The average error for the predictions of the final tumor volume was 12%, with the true volumes always bounded by the 95% confidence interval. The greatest model uncertainty occurred near the middle of the course of treatment, in which the tumor response relationships were more complex, the model has less information, and the predictors were more varied. The optimal days for measuring the tumor response on the MVCT images were on elapsed Days 1, 2, 5, 9, 11, 12, 17, and 18 during

  4. 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.

  5. Variable fitness impact of HIV-1 escape mutations to cytotoxic T lymphocyte (CTL response.

    Directory of Open Access Journals (Sweden)

    Ryan M Troyer

    2009-04-01

    Full Text Available Human lymphocyte antigen (HLA-restricted CD8(+ cytotoxic T lymphocytes (CTL target and kill HIV-infected cells expressing cognate viral epitopes. This response selects for escape mutations within CTL epitopes that can diminish viral replication fitness. Here, we assess the fitness impact of escape mutations emerging in seven CTL epitopes in the gp120 Env and p24 Gag coding regions of an individual followed longitudinally from the time of acute HIV-1 infection, as well as some of these same epitopes recognized in other HIV-1-infected individuals. Nine dominant mutations appeared in five gp120 epitopes within the first year of infection, whereas all four mutations found in two p24 epitopes emerged after nearly two years of infection. These mutations were introduced individually into the autologous gene found in acute infection and then placed into a full-length, infectious viral genome. When competed against virus expressing the parental protein, fitness loss was observed with only one of the nine gp120 mutations, whereas four had no effect and three conferred a slight increase in fitness. In contrast, mutations conferring CTL escape in the p24 epitopes significantly decreased viral fitness. One particular escape mutation within a p24 epitope was associated with reduced peptide recognition and high viral fitness costs but was replaced by a fitness-neutral mutation. This mutation appeared to alter epitope processing concomitant with a reduced CTL response. In conclusion, CTL escape mutations in HIV-1 Gag p24 were associated with significant fitness costs, whereas most escape mutations in the Env gene were fitness neutral, suggesting a balance between immunologic escape and replicative fitness costs.

  6. HIV RNA and proviral HIV DNA can be detected in semen after 6 months of antiretroviral therapy although HIV RNA is undetectable in blood.

    Science.gov (United States)

    Du, Peiwei; Liu, An; Jiao, Yanmei; Liu, Cuie; Jiang, Taiyi; Zhu, Weijun; Zhu, Yunxia; Wu, Hao; Sun, Lijun

    2016-03-01

    The risk of sexual transmission of HIV is strongly correlated with amounts of genital HIV RNA. Few studies have reported amounts of HIV RNA and HIV DNA in semen in HIV-infected Chinese patients undergoing antiviral treatment (ART). In this observational study, the amounts of HIV RNA and HIV DNA in semen were assessed after six months of ART in HIV-infected Chinese individuals, when HIV RNA was undetectable in blood . This study included 19 HIV-infected Chinese men undergoing ART for six months. Amounts of HIV in paired semen and blood samples were assessed using real-time PCR. The C2-V5 region of the HIV envelope (env) genes was cloned and sequenced and genotype and co-receptor usage predicted based on the sequence. It was found that HIV RNA was undetectable in the plasma of most patients (17/19), whereas HIV RNA could be detected in the semen of most patients (16/19). HIV DNA could be detected in both semen and blood. Genetic diversity of HIV between the seminal and blood compartments was identified. Thus, amounts of HIV RNA and HIV DNA remain high in semen of HIV-infected Chinese patients after six months of ART treatment, even when HIV RNA was undetectable in blood. © 2016 The Societies and John Wiley & Sons Australia, Ltd.

  7. Symptom Status Predicts Patient Outcomes in Persons with HIV and Comorbid Liver Disease

    Directory of Open Access Journals (Sweden)

    Wendy A. Henderson

    2012-01-01

    Full Text Available Persons living with human immunodeficiency virus (HIV are living longer; therefore, they are more likely to suffer significant morbidity due to potentially treatable liver diseases. Clinical evidence suggests that the growing number of individuals living with HIV and liver disease may have a poorer health-related quality of life (HRQOL than persons living with HIV who do not have comorbid liver disease. Thus, this study examined the multiple components of HRQOL by testing Wilson and Cleary’s model in a sample of 532 individuals (305 persons with HIV and 227 persons living with HIV and liver disease using structural equation modeling. The model components include biological/physiological factors (HIV viral load, CD4 counts, symptom status (Beck Depression Inventory II and the Medical Outcomes Study HIV Health Survey (MOS-HIV mental function, functional status (missed appointments and MOS-HIV physical function, general health perceptions (perceived burden visual analogue scale and MOS-HIV health transition, and overall quality of life (QOL (Satisfaction with Life Scale and MOS-HIV overall QOL. The Wilson and Cleary model was found to be useful in linking clinical indicators to patient-related outcomes. The findings provide the foundation for development and future testing of targeted biobehavioral nursing interventions to improve HRQOL in persons living with HIV and liver disease.

  8. Resource flows and levels of spending for the response to HIV and AIDS in Belarus

    Directory of Open Access Journals (Sweden)

    Amico Peter

    2011-07-01

    Full Text Available Abstract Background Belarus has a focused HIV epidemic concentrated among injecting drug users, female sex workers and men who have sex with men. However, until 2008, Belarus had no way of evaluating HIV spending priorities. In 2008, Belarus committed to undertaking a comprehensive National AIDS Spending Assessment (NASA in order to analyze HIV spending priorities. NASA was used to 'follow the money' from the funding sources to agents and providers, and eventually to beneficiary populations. Findings Belarus spent the majority of its funding on prevention, diagnosis and treatment of sexually transmitted infections and on securing the blood supply. International donors and NGOs working within Belarus spent the majority of their funding on preventative activities for high risk groups while Global Fund to Fight AIDS, Tuberculosis, and Malaria (GFATM solely funded antiretroviral treatment. Conclusions The data and experience obtained through conducting NASA will help build capacity for future resource tracking activities for HIV and other health priorities. This experience established the foundation for enhanced and future consistent quality-reporting of National Health Accounts. Monitoring the flow of resources for Belarus' HIV response provides valuable strategic information that can improve operations and planning as well as mobilize greater resources. NASA offers Belarusian policy makers an overview of HIV activities that merit their priority attention. In addition, the findings from Belarus are particularly relevant for the rest of the Commonwealth of Independent States due to their similar epidemiological profiles and centrally planned systems. The Belarusian government faces future challenges, especially in increasing public investments in HIV prevention for female sex workers and their clients, men who have sex with men, and among intravenous drug users.

  9. HIV Prevalence Trends, Risky Behaviours, and Governmental and Community Responses to the Epidemic among Men Who Have Sex with Men in China

    Directory of Open Access Journals (Sweden)

    Eric P. F. Chow

    2014-01-01

    Full Text Available Purpose of Review. Numerous studies reported the rapid spread of HIV/AIDS epidemic among men who have sex with men (MSM in China. This paper aims to investigate the overall epidemic trend and associated high-risk behaviours among Chinese MSM and to explore the governmental and community responses to the epidemic. Recent Findings. HIV prevalence among Chinese MSM increased rapidly in all Chinese regions in the past decade and disproportionally affected the Southwest China. In addition to the high-risk homosexual behaviours, overlapping bisexual, commercial, and drug use behaviours are commonly observed among Chinese MSM. The Chinese government has significantly expanded the surveillance efforts among MSM over the past decade. Community responses against HIV have been substantially strengthened with the support of international aid. However, lack of enabling legal and financial environment undermines the role of community-based organisations (CBOs in HIV surveillance and prevention. Conclusion. HIV continues to spread rapidly among MSM in China. The hidden nature of MSM and the overlapping homosexual, bisexual, and commercial behaviours remain a challenge for HIV prevention among MSM. Strong collaboration between the government and CBOs and innovative intervention approaches are essential for effective HIV surveillance and prevention among MSM in China.

  10. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... response to HIV/AIDS, as well as HIV/AIDS research and policies. AIDS.gov New Media Tools : These new media tools ... offers access to the latest, federally approved HIV/AIDS medical practice ... information for health care providers, researchers, people affected ...

  11. Association of Internalized and Social Network Level HIV Stigma With High-Risk Condomless Sex Among HIV-Positive African American Men

    OpenAIRE

    Wagner, Glenn J.; Bogart, Laura M.; Klein, David J.; Green, Harold D.; Mutchler, Matt G.; McDavitt, Bryce; Hilliard, Charles

    2015-01-01

    We examined whether internalized HIV stigma and perceived HIV stigma from social network members (alters), including the most popular and most similar alter, predicted condomless intercourse with negative or unknown HIV status partners among 125 African American HIV-positive men. In a prospective, observational study, participants were administered surveys at baseline and months 6 and 12, with measures including sexual behavior, internalized HIV stigma, and an egocentric social network assess...

  12. A community empowerment approach to the HIV response among sex workers: effectiveness, challenges, and considerations for implementation and scale-up.

    Science.gov (United States)

    Kerrigan, Deanna; Kennedy, Caitlin E; Morgan-Thomas, Ruth; Reza-Paul, Sushena; Mwangi, Peninah; Win, Kay Thi; McFall, Allison; Fonner, Virginia A; Butler, Jennifer

    2015-01-10

    A community empowerment-based response to HIV is a process by which sex workers take collective ownership of programmes to achieve the most effective HIV outcomes and address social and structural barriers to their overall health and human rights. Community empowerment has increasingly gained recognition as a key approach for addressing HIV in sex workers, with its focus on addressing the broad context within which the heightened risk for infection takes places in these individuals. However, large-scale implementation of community empowerment-based approaches has been scarce. We undertook a comprehensive review of community empowerment approaches for addressing HIV in sex workers. Within this effort, we did a systematic review and meta-analysis of the effectiveness of community empowerment in sex workers in low-income and middle-income countries. We found that community empowerment-based approaches to addressing HIV among sex workers were significantly associated with reductions in HIV and other sexually transmitted infections, and with increases in consistent condom use with all clients. Despite the promise of a community-empowerment approach, we identified formidable structural barriers to implementation and scale-up at various levels. These barriers include regressive international discourses and funding constraints; national laws criminalising sex work; and intersecting social stigmas, discrimination, and violence. The evidence base for community empowerment in sex workers needs to be strengthened and diversified, including its role in aiding access to, and uptake of, combination interventions for HIV prevention. Furthermore, social and political change are needed regarding the recognition of sex work as work, both globally and locally, to encourage increased support for community empowerment responses to HIV. Copyright © 2015 Elsevier Ltd. All rights reserved.

  13. Characterization of HIV-Specific CD4+T Cell Responses against Peptides Selected with Broad Population and Pathogen Coverage

    DEFF Research Database (Denmark)

    Buggert, Marcus; Norstrom, Melissa M.; Czarnecki, Chris

    2012-01-01

    for the identification of HIV-specific CD4+ T cells targeting broadly reactive epitopes in populations with diverse ethnic background stems from the vast genomic variation of HIV and the diversity of the host cellular immune system. Here, we describe a novel epitope selection strategy, PopCover, that aims to resolve...... this challenge, and identify a set of potential HLA class II-restricted HIV epitopes that in concert will provide optimal viral and host coverage. Using this selection strategy, we identified 64 putative epitopes (peptides) located in the Gag, Nef, Env, Pol and Tat protein regions of HIV. In total, 73...... II-restricted epitopes. All together, selection strategies, such as PopCover, might with success be used for the evaluation of antigen-specific CD4+ T cell responses and design of future vaccines....

  14. Characterization of broadly neutralizing antibody responses to HIV-1 in a cohort of long term non-progressors.

    Science.gov (United States)

    González, Nuria; McKee, Krisha; Lynch, Rebecca M; Georgiev, Ivelin S; Jimenez, Laura; Grau, Eulalia; Yuste, Eloísa; Kwong, Peter D; Mascola, John R; Alcamí, José

    2018-01-01

    Only a small fraction of HIV-1-infected patients develop broadly neutralizing antibodies (bNAbs), a process generally associated to chronic antigen stimulation. It has been described that rare aviremic HIV-1-infected patients can generate bNAbs but this issue remains controversial. To address this matter we have assessed bNAb responses in a large cohort of long-term non-progressors (LTNPs) with low or undetectable viremia. Samples from the LTNP cohort of the Spanish AIDS Research Network (87 elite and 42 viremic controllers) and a control population of 176 viremic typical-progressors (TPs) were screened for bNAbs using Env-recombinant viruses. bNAb specificities were studied by ELISA using mutated gp120, neutralization assays with mutated viruses, and peptide competition. Epitope specificities were also elucidated from the serum pattern of neutralization against a panel of diverse HIV-1 isolates. Broadly neutralizing sera were found among 9.3% LTNPs, both elite (7%) and viremic controllers (14%). Within the broadly neutralizing sera, CD4 binding site antibodies were detected by ELISA in 4/12 LTNPs (33%), and 16/33 of TPs (48%). Anti-MPER antibodies were detected in 6/12 LTNPs (50%) and 14/33 TPs (42%) whereas glycan-dependent HIV-1 bNAbs were more frequent in LTNPs (11/12, 92%) as compared to TPs (12/33, 36%). A good concordance between standard serum mapping and neutralization-based mapping was observed. LTNPs, both viremic and elite controllers, showed broad humoral immune responses against HIV-1, including activity against many major epitopes involved in bNAbs-mediated protection.

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

    Science.gov (United States)

    Reniers, Georges; Armbruster, Benjamin

    2012-01-01

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

  16. Simplifying consent for HIV testing is associated with an increase in HIV testing and case detection in highest risk groups, San Francisco January 2003-June 2007.

    Directory of Open Access Journals (Sweden)

    Nicola M Zetola

    2008-07-01

    Full Text Available Populations at highest risk for HIV infection face multiple barriers to HIV testing. To facilitate HIV testing procedures, the San Francisco General Hospital Medical Center eliminated required written patient consent for HIV testing in its medical settings in May 2006. To describe the change in HIV testing rates in different hospital settings and populations after the change in HIV testing policy in the SFDH medical center, we performed an observational study using interrupted time series analysis.Data from all patients aged 18 years and older seen from January 2003 through June 2007 at the San Francisco Department of Public Health (SFDPH medical care system were included in the analysis. The monthly HIV testing rate per 1000 had patient-visits was calculated for the overall population and stratified by hospital setting, age, sex, race/ethnicity, homelessness status, insurance status and primary language.By June 2007, the average monthly rate of HIV tests per 1000 patient-visits increased 4.38 (CI, 2.17-6.60, p<0.001 over the number predicted if the policy change had not occurred (representing a 44% increase. The monthly average number of new positive HIV tests increased from 8.9 (CI, 6.3-11.5 to 14.9 (CI, 10.6-19.2, p<0.001, representing a 67% increase. Although increases in HIV testing were seen in all populations, populations at highest risk for HIV infection, particularly men, the homeless, and the uninsured experienced the highest increases in monthly HIV testing rates after the policy change.The elimination of the requirement for written consent in May 2006 was associated with a significant and sustained increase in HIV testing rates and HIV case detection in the SFDPH medical center. Populations facing the higher barriers to HIV testing had the highest increases in HIV testing rates and case detection in response to the policy change.

  17. Distinct susceptibility of HIV vaccine vector-induced CD4 T cells to HIV infection

    Science.gov (United States)

    Niu, Qingli; Hou, Wei; Churchyard, Gavin; Nitayaphan, Sorachai; Pitisuthithum, Punnee; Rerks-Ngarm, Supachai; Franchini, Genoveffa

    2018-01-01

    The concerns raised from adenovirus 5 (Ad5)-based HIV vaccine clinical trials, where excess HIV infections were observed in some vaccine recipients, have highlighted the importance of understanding host responses to vaccine vectors and the HIV susceptibility of vector-specific CD4 T cells in HIV vaccination. Our recent study reported that human Ad5-specific CD4 T cells induced by Ad5 vaccination (RV156A trial) are susceptible to HIV. Here we further investigated the HIV susceptibility of vector-specific CD4 T cells induced by ALVAC, a canarypox viral vector tested in the Thai trial RV144, as compared to Ad5 vector-specific CD4 T cells in the HVTN204 trial. We showed that while Ad5 vector-specific CD4 T cells were readily susceptible to HIV, ALVAC-specific CD4 T cells in RV144 PBMC were substantially less susceptible to both R5 and X4 HIV in vitro. The lower HIV susceptibility of ALVAC-specific CD4 T cells was associated with the reduced surface expression of HIV entry co-receptors CCR5 and CXCR4 on these cells. Phenotypic analyses identified that ALVAC-specific CD4 T cells displayed a strong Th1 phenotype, producing higher levels of IFN-γ and CCL4 (MIP-1β) but little IL-17. Of interest, ALVAC and Ad5 vectors induced distinct profiles of vector-specific CD8 vs. CD4 T-cell proliferative responses in PBMC, with ALVAC preferentially inducing CD8 T-cell proliferation, while Ad5 vector induced CD4 T-cell proliferation. Depletion of ALVAC-, but not Ad5-, induced CD8 T cells in PBMC led to a modest increase in HIV infection of vector-specific CD4 T cells, suggesting a role of ALVAC-specific CD8 T cells in protecting ALVAC-specific CD4 T cells from HIV. Taken together, our data provide strong evidence for distinct HIV susceptibility of CD4 T cells induced by different vaccine vectors and highlight the importance of better evaluating anti-vector responses in HIV vaccination. PMID:29474461

  18. Parenting and HIV.

    Science.gov (United States)

    Rochat, Tamsen; Netsi, Elena; Redinger, Stephanie; Stein, Alan

    2017-06-01

    With the widespread use of antiretroviral therapy and successful prevention of mother-to-child transmission the development of HIV-negative children with HIV-positive parents has become an important focus. There is considerable evidence that children's developmental risk is heightened because a parental HIV-diagnosis is associated with a range of potential problems such as depression, stigma and financial difficulties. Up to a third of children in sub-Saharan Africa (SSA) are cared for by an HIV-positive parent or caregiver. We review the mechanisms by which HIV affects parenting including its negative effects on parental responsiveness in the early years of parenting and parental avoidant coping styles and parenting deficits in the later years. We describe low-cost parenting interventions suited for low resourced HIV endemic settings. Copyright © 2017. Published by Elsevier Ltd.

  19. Association of Internalized and Social Network Level HIV Stigma With High-Risk Condomless Sex Among HIV-Positive African American Men.

    Science.gov (United States)

    Wagner, Glenn J; Bogart, Laura M; Klein, David J; Green, Harold D; Mutchler, Matt G; McDavitt, Bryce; Hilliard, Charles

    2016-08-01

    We examined whether internalized HIV stigma and perceived HIV stigma from social network members (alters), including the most popular and most similar alter, predicted condomless intercourse with negative or unknown HIV status partners among 125 African American HIV-positive men. In a prospective, observational study, participants were administered surveys at baseline and months 6 and 12, with measures including sexual behavior, internalized HIV stigma, and an egocentric social network assessment that included several measures of perceived HIV stigma among alters. In longitudinal multivariable models comparing the relative predictive value of internalized stigma versus various measures of alter stigma, significant predictors of having had condomless intercourse included greater internalized HIV stigma (in all models), the perception that a popular (well-connected) alter or alter most like the participant agrees with an HIV stigma belief, and the interaction of network density with having any alter that agrees with a stigma belief. The interaction indicated that the protective effect of greater density (connectedness between alters) in terms of reduced risk behavior dissipated in the presence of perceived alter stigma. These findings call for interventions that help people living with HIV to cope with their diagnosis and reduce stigma, and inform the targets of social network-based and peer-driven HIV prevention interventions.

  20. Strengthening Routine Data Systems to Track the HIV Epidemic and Guide the Response in Sub-Saharan Africa.

    Science.gov (United States)

    Rice, Brian; Boulle, Andrew; Baral, Stefan; Egger, Matthias; Mee, Paul; Fearon, Elizabeth; Reniers, Georges; Todd, Jim; Schwarcz, Sandra; Weir, Sharon; Rutherford, George; Hargreaves, James

    2018-04-03

    The global HIV response has entered a new phase with the recommendation of treating all persons living with HIV with antiretroviral therapy, and with the goals of reducing new infections and AIDS-related deaths to fewer than 500,000 by 2020. This new phase has intensive data requirements that will need to utilize routine data collected through service delivery platforms to monitor progress toward these goals. With a focus on sub-Saharan African, we present the following priorities to improve the demand, supply, and use of routine HIV data: (1) strengthening patient-level HIV data systems that support continuity of clinical care and document sentinel events; (2) leveraging data from HIV testing programs; (3) using targeting data collection in communities and among clients; and (4) building capacity and promoting a culture of HIV data quality assessment and use. When fully leveraged, routine data can efficiently provide timely information at a local level to inform action, as well as provide information at scale with wide geographic coverage to strengthen estimation efforts. ©Brian Rice, Andrew Boulle, Stefan Baral, Matthias Egger, Paul Mee, Elizabeth Fearon, Georges Reniers, Jim Todd, Sandra Schwarcz, Sharon Weir, George Rutherford, James Hargreaves. Originally published in JMIR Public Health and Surveillance (http://publichealth.jmir.org), 03.04.2018.

  1. Know your epidemic, know your response: targeting HIV in Asia

    DEFF Research Database (Denmark)

    Lazarus, Jeff; Curth, Nadja; Bridge, Jamie

    2010-01-01

    This article provides an overview of the HIV epidemic in Asia, the context within which the epidemic is evolving, and the key actions to address the challenges faced by countries and risk groups. HIV epidemics across Asia are predominantly concentrated among most-at-risk populations. Although...... prevention and treatment services. In order to reach the Millennium Development Goal of halting and reversing the spread of HIV by 2015 and to achieve universal access to HIV treatment, these barriers must be overcome across Asia. High-impact programs must be targeted at those in need, with continuous...

  2. Morality, responsibility and risk: negative gay men's perceived proximity to HIV.

    Science.gov (United States)

    Keogh, Peter

    2008-05-01

    In order to examine the ways in which men's perceptions of their social surroundings influence how they experience and negotiate sexual risk, we conducted a qualitative study with 36 men who lived in London or Birmingham, had five or more male partners in the previous year and believed themselves to be HIV negative. Men were recruited into two sub-samples (18 men each). The high proximity group personally knew someone with HIV and had a positive sexual partner in the year prior to interview. The low proximity group had never personally known anyone with HIV and had never had a sexual partner who they knew or believed to be HIV positive. Data was collected via semi-structured interviews. Men in the low proximity groups used moral discourses to articulate beliefs and social norms around the disclosure of HIV which may act as a deterrent to sexual partners disclosing. Although most expected positive sexual partners to disclose, they had difficulty in articulating how they would respond to disclosure and how they would manage any consequent sexual risk. For the men in the high proximity group, living around HIV constituted a part of everyday life. Disclosure and discussion of HIV did not violate their social norms. The majority did not expect positive sexual partners to disclose to them and knew how they would respond to such disclosure if it occurred. Men in this group did not use moral discourses but talked practically about better and worse ways of managing disclosure. Proximity to HIV is mediated by strong social norms and self-perpetuating moral discourses which effectively creates a social divide between men who perceive themselves to be in low proximity to HIV and their HIV positive contacts and sexual partners. Men with perceived low proximity to HIV are appropriate as a target group for HIV prevention.

  3. Assessment of Oral Fluid HIV Test Performance in an HIV Pre-Exposure Prophylaxis Trial in Bangkok, Thailand.

    Directory of Open Access Journals (Sweden)

    Pravan Suntharasamai

    Full Text Available Rapid easy-to-use HIV tests offer opportunities to increase HIV testing among populations at risk of infection. We used the OraQuick Rapid HIV-1/2 antibody test (OraQuick in the Bangkok Tenofovir Study, an HIV pre-exposure prophylaxis trial among people who inject drugs.The Bangkok Tenofovir Study was a randomized, double-blind, placebo-controlled trial. We tested participants' oral fluid for HIV using OraQuick monthly and blood using a nucleic-acid amplification test (NAAT every 3 months. We used Kaplan-Meier methods to estimate the duration from a positive HIV NAAT until the mid-point between the last non-reactive and first reactive oral fluid test and proportional hazards to examine factors associated with the time until the test was reactive.We screened 3678 people for HIV using OraQuick. Among 447 with reactive results, 436 (97.5% were confirmed HIV-infected, 10 (2.2% HIV-uninfected, and one (0.2% had indeterminate results. Two participants with non-reactive OraQuick results were, in fact, HIV-infected at screening yielding 99.5% sensitivity, 99.7% specificity, a 97.8% positive predictive value, and a 99.9% negative predictive value. Participants receiving tenofovir took longer to develop a reactive OraQuick (191.8 days than participants receiving placebo (16.8 days (p = 0.02 and participants infected with HIV CRF01_AE developed a reactive OraQuick earlier than participants infected with other subtypes (p = 0.04.The oral fluid HIV test performed well at screening, suggesting it can be used when rapid results and non-invasive tools are preferred. However, participants receiving tenofovir took longer to develop a reactive oral fluid test result than those receiving placebo. Thus, among people using pre-exposure prophylaxis, a blood-based HIV test may be an appropriate choice.ClinicalTrials.gov NCT00119106.

  4. Living with HIV: Patients Perspective

    Centers for Disease Control (CDC) Podcasts

    2009-06-04

    This podcast showcases three people who are living with HIV. The patients share their experiences of being diagnosed with HIV, of the treatments they are undergoing, and on taking responsibility for their health.  Created: 6/4/2009 by Division of HIV and AIDS Prevention (DHAP), National Center for HIV, Hepatitis, STD, and Tuberculosis Prevention ( NCHHSTP).   Date Released: 6/4/2009.

  5. Education about HIV/AIDS--Theoretical Underpinnings for a Practical Response

    Science.gov (United States)

    Miedema, Esther A. J.; Maxwell, Claire; Aggleton, Peter

    2011-01-01

    Human immunodeficiency virus (HIV)- and acquired immunodeficiency syndrome (AIDS)-related education is seen by many as central to increasing young people's awareness of, as well as decreasing their vulnerability to, HIV. There is less agreement, however, on the central goals of HIV- and AIDS-related education and the form it might best take. This…

  6. Prediction of Risk Behaviors in HIV-infected Patients Based on Family Functioning: The Mediating Roles of Lifestyle and Risky Decision Making

    Directory of Open Access Journals (Sweden)

    Fariba Ebrahim Babaei

    2017-09-01

    Full Text Available Background and Objective: Risk behaviors are more common in the HIV-positive patients than that in the general population. These behaviors are affected by various factors, such as biological, familial, and social determinants, peer group, media, and lifestyle. Low family functioning is one of the important factors predicting risk behaviors. Regarding this, the present study aimed to investigate the role of family functioning in predicting risk behaviors in the HIV-infected patients based on the mediating roles of risky decision making and lifestyle. Materials and Methods: This descriptive correlational study was conducted on 147 HIV-positive patients selected through convenience sampling technique. The data were collected using the health promoting lifestyle profile-2 (HPLP-2, family adaptability and cohesion scale IV (FACES-IV, balloon analogue risk task (BART, and risk behavior assessment in social situation. The data were analyzed using structural equation modeling method in LISREL 8.8 software. Results: According to the results, there was an indirect relationship between family functioning and risk behaviors. Furthermore, family functioning both directly and indirectly affected the risk behaviors through two mediators of lifestyle and risky decision making. Conclusion: As the findings indicated, family functioning directly contributed to risk behaviors. Moreover, this variable indirectly affected risk behaviors through the mediating roles of risky decision making and lifestyle. Consequently, the future studies should focus more deeply on family functioning role in the risk behaviors of the HIV-infected patients.

  7. Effect of Pregnancy on Response to Antiretroviral Therapy in HIV-Infected African Women.

    Science.gov (United States)

    Kourtis, Athena P; Wiener, Jeffrey; King, Caroline C; Heffron, Renee; Mugo, Nelly R; Nanda, Kavita; Pyra, Maria; Donnell, Deborah; Celum, Connie; Lingappa, Jairam R; Baeten, Jared M

    2017-01-01

    While most recent evidence does not support a role for pregnancy in accelerating HIV disease progression, very little information is available on the effects of incident pregnancy in response to antiretroviral therapy (ART). Hormonal, immune, and behavioral changes during pregnancy may influence response to ART. We sought to explore the effects of incident pregnancy (after ART initiation) on virologic, immunologic, and clinical response to ART. Data were collected from HIV-infected women participating in 3 prospective studies (Partners in Prevention Herpes simplex virus/HIV Transmission Study, Couples Observational Study, and Partners Preexposure Prophylaxis Study) from 7 countries in Africa from 2004 to 2012. Women were included in this analysis if they were ≤45 years of age, were started on ART during the study and were not pregnant at ART initiation. Pregnancy was treated as a time-dependent exposure variable covering the duration of pregnancy, including all pregnancies occurring after ART initiation. Virologic failure was defined as a viral load (VL) greater than 400 copies per milliliter ≥6 months after ART initiation and viral suppression was defined as VL ≤400 copies per milliliter. Multivariable Cox proportional hazards models were used to assess the association between pregnancy and time to viral suppression, virologic failure, World Health Organization clinical stage III/IV, and death. Linear mixed-effects models were used to assess the association between pregnancy and CD4 count and VL. All analyses were adjusted for confounders, including pre-ART CD4 count and plasma VL. A total of 1041 women were followed, contributing 1196.1 person-years of follow-up. Median CD4 count before ART initiation was 276 cells per cubic millimeter (interquartile range, 209-375); median pre-ART VL was 17,511 copies per milliliter (interquartile range, 2480-69,286). One hundred ten women became pregnant after ART initiation. Pregnancy was not associated with time to

  8. Predicting long-term outcomes for children affected by HIV and AIDS: perspectives from the scientific study of children's development.

    Science.gov (United States)

    Stein, Alan; Desmond, Christopher; Garbarino, James; Van IJzendoorn, Marinus H; Barbarin, Oscar; Black, Maureen M; Stein, Aryeh D; Hillis, Susan D; Kalichman, Seth C; Mercy, James A; Bakermans-Kranenburg, Marian J; Rapa, Elizabeth; Saul, Janet R; Dobrova-Krol, Natasha A; Richter, Linda M

    2014-07-01

    The immediate and short-term consequences of adult HIV for affected children are well documented. Little research has examined the long-term implications of childhood adversity stemming from caregiver HIV infection. Through overviews provided by experts in the field, together with an iterative process of consultation and refinement, we have extracted insights from the broader field of child development of relevance to predicting the long-term consequences to children affected by HIV and AIDS. We focus on what is known about the impact of adversities similar to those experienced by HIV-affected children, and for which there is longitudinal evidence. Cautioning that findings are not directly transferable across children or contexts, we examine findings from the study of parental death, divorce, poor parental mental health, institutionalization, undernutrition, and exposure to violence. Regardless of the type of adversity, the majority of children manifest resilience and do not experience any long-term negative consequences. However, a significant minority do and these children experience not one, but multiple problems, which frequently endure over time in the absence of support and opportunities for recovery. As a result, they are highly likely to suffer numerous and enduring impacts. These insights suggest a new strategic approach to interventions for children affected by HIV and AIDS, one that effectively combines a universal lattice of protection with intensive intervention targeted to selected children and families.

  9. Immunoglobulin G1 Allotype Influences Antibody Subclass Distribution in Response to HIV gp140 Vaccination

    Directory of Open Access Journals (Sweden)

    Sven Kratochvil

    2017-12-01

    Full Text Available Antibody subclasses exhibit extensive polymorphisms (allotypes that could potentially impact the quality of HIV-vaccine induced B cell responses. Allotypes of immunoglobulin (Ig G1, the most abundant serum antibody, have been shown to display altered functional properties in regard to serum half-life, Fc-receptor binding and FcRn-mediated mucosal transcytosis. To investigate the potential link between allotypic IgG1-variants and vaccine-generated humoral responses in a cohort of 14 HIV vaccine recipients, we developed a novel protocol for rapid IgG1-allotyping. We combined PCR and ELISA assays in a dual approach to determine the IgG1 allotype identity (G1m3 and/or G1m1 of trial participants, using human plasma and RNA isolated from PBMC. The IgG1-allotype distribution of our participants mirrored previously reported results for caucasoid populations. We observed elevated levels of HIV gp140-specific IgG1 and decreased IgG2 levels associated with the G1m1-allele, in contrast to G1m3 carriers. These data suggest that vaccinees homozygous for G1m1 are predisposed to develop elevated Ag-specific IgG1:IgG2 ratios compared to G1m3-carriers. This elevated IgG1:IgG2 ratio was further associated with higher FcγR-dimer engagement, a surrogate for potential antibody-dependent cellular cytotoxicity (ADCC and antibody-dependent cellular phagocytosis (ADCP function. Although preliminary, these results suggest that IgG1 allotype may have a significant impact on IgG subclass distribution in response to vaccination and associated Fc-mediated effector functions. These results have important implications for ongoing HIV vaccine efficacy studies predicated on engagement of FcγR-mediated cellular functions including ADCC and ADCP, and warrant further investigation. Our novel allotyping protocol provides new tools to determine the potential impact of IgG1 allotypes on vaccine efficacy.

  10. Drug resistance in HIV patients with virological failure or slow virological response to antiretroviral therapy in Ethiopia

    DEFF Research Database (Denmark)

    Abdissa, Alemseged; Yilma, Daniel; Fonager, Jannik

    2014-01-01

    BACKGROUND: The ongoing scale-up of antiretroviral therapy (ART) in sub-Saharan Africa has prompted the interest in surveillance of transmitted and acquired HIV drug resistance. Resistance data on virological failure and mutations in HIV infected populations initiating treatment in sub-Saharan Af...... mutations among failing patients justify increased vigilance by improving the availability and systematic use of VL testing to monitor ART response, and underlines the need for rapid, inexpensive tests to identify the most common drug resistance mutations....

  11. T-cell subset alterations and lymphocyte responsiveness to mitogens and antigen during severe primary infection with HIV: a case series of seven consecutive HIV seroconverters

    DEFF Research Database (Denmark)

    Pedersen, C; Dickmeiss, E; Gaub, J

    1990-01-01

    Seven consecutive patients who presented with a severe acute mononucleosis-like illness associated with HIV seroconversion were evaluated by T-cell subset enumerations and measurements of lymphocyte transformation responses to mitogens and antigen during both their primary illness and a 1-year...

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

    Directory of Open Access Journals (Sweden)

    Georges Reniers

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

  13. Epstein-Barr virus and human immunodeficiency virus serological responses and viral burdens in HIV-infected patients treated with HAART

    Science.gov (United States)

    O'Sullivan, Cathal E.; Peng, RongSheng; Cole, Kelly Stefano; Montelaro, Ronald C.; Sturgeon, Timothy; Jenson, Hal B.; Ling, Paul D.; Butel, J. S. (Principal Investigator)

    2002-01-01

    Epstein-Barr virus (EBV) associated non-Hodgkin lymphoma is recognized as a complication of human immunodeficiency virus (HIV) infection. Little is known regarding the influence of highly active antiretroviral therapy (HAART) on the biology of EBV in this population. To characterize the EBV- and HIV-specific serological responses together with EBV DNA levels in a cohort of HIV-infected adults treated with HAART, a study was conducted to compare EBV and HIV serologies and EBV DNA copy number (DNAemia) over a 12-month period after the commencement of HAART. All patients were seropositive for EBV at baseline. Approximately 50% of patients had detectable EBV DNA at baseline, and 27/30 had detectable EBV DNA at some point over the follow-up period of 1 year. Changes in EBV DNA copy number over time for any individual were unpredictable. Significant increases in the levels of Epstein-Barr nuclear antigen (EBNA) and Epstein-Barr early antigen (EA) antibodies were demonstrated in the 17 patients who had a good response to HAART. Of 29 patients with paired samples tested, four-fold or greater increases in titers were detected for EA in 12/29 (41%), for EBNA in 7/29 (24%), for VCA-IgG in 4/29 (14%); four-fold decreases in titers were detected in 2/29 (7%) for EA and 12/29 (41%) for EBNA. A significant decline in the titer of anti-HIV antibodies was also demonstrated. It was concluded that patients with advanced HIV infection who respond to HAART have an increase in their EBV specific antibodies and a decrease in their HIV-specific antibodies. For the cohort overall, there was a transient increase in EBV DNA levels that had declined by 12 months. Copyright 2002 Wiley-Liss, Inc.

  14. The developmental effects of HIV and alcohol: a comparison of gestational outcomes among babies from South African communities with high prevalence of HIV and alcohol use.

    Science.gov (United States)

    Donald, Kirsten A M; Fernandez, Anne; Claborn, Kasey; Kuo, Caroline; Koen, Nastassja; Zar, Heather; Stein, Dan J

    2017-05-08

    There is growing evidence of the negative impact of alcohol on morbidity and mortality of individuals living with HIV but limited evidence of in utero effects of HIV and alcohol on exposure on infants. We conducted a population-based birth cohort study (N = 667 mother-infant dyads) in South Africa to investigate whether maternal alcohol use and HIV affected gestational outcomes. Descriptive data analysis was conducted for all variables using frequency distributions, measures of central tendency, and estimates of variance. Hierarchical multiple regression was conducted to determine whether maternal alcohol use, maternal HIV status and other risk factors (socioeconomic status, smoking, depression) predicted infant outcomes. Our results showed severity of recent alcohol use and lifetime alcohol use predicted low birth weight. Similarly lifetime alcohol use predicted shorter infant length, smaller head length, smaller head circumference, and early gestational age. However, HIV status was not a significant predictor of gestational outcomes. The unexpected finding that maternal HIV status did not predict any of the gestational outcomes may be due to high rates of ART usage among HIV-infected mothers. The potentially negative effects of HIV on gestational outcomes may have been attenuated by improved maternal health due to high coverage of antiretroviral treatment in South Africa. Interventions are needed to reduce alcohol consumption among pregnant mothers and to support healthy growth and psychosocial development of infants.

  15. Identifying structural barriers to an effective HIV response: using the National Composite Policy Index data to evaluate the human rights, legal and policy environment

    Science.gov (United States)

    Gruskin, Sofia; Ferguson, Laura; Alfven, Tobias; Rugg, Deborah; Peersman, Greet

    2013-01-01

    Introduction Attention to the negative effects of structural barriers on HIV efforts is increasing. Reviewing national legal and policy environments with attention to the international human rights commitments of states is a means of assessing and providing focus for addressing these barriers to effective HIV responses. Methods Law and policy data from the 171 countries reporting under the Declaration of Commitment from the 2001 United Nations General Assembly Special Session on HIV/AIDS were analyzed to assess attention to human rights in national legal and policy environments as relevant to the health and rights of key populations such as people who inject drugs, men who have sex with men and sex workers. Results Seventy-eight governments and civil society in 106 countries report the existence of laws and policies which present obstacles to accessing HIV services for key populations. Laws and policies which positively affect access to HIV-related services, in and of themselves constituting structural interventions, were also reported. The dissonance between laws and how this impacts the availability and use of HIV-related services deserve greater attention. Conclusions Recognition of the harms inherent in laws that constitute structural barriers to effective HIV responses and the potential positive role that a supportive legal environment can play suggests the need for legal reform to ensure an enabling regulatory framework within which HIV services can be effectively delivered and used by the populations who need them. Moving beyond laws and policies, further efforts are required to determine how to capture information on the range of structural barriers. Teasing apart the impact of different barriers, as well as the structural interventions put in place to address them, remains complicated. Capturing the impact of policy and legal interventions can ultimately support governments and civil society to ensure the human rights of key populations are protected in

  16. Traditional healers, HIV/AIDS and company programmes in South ...

    African Journals Online (AJOL)

    Traditional healers' diverse and fluid beliefs about HIV and AIDS are ... healing practices could be promoted in workplace responses to HIV/AIDS. ... as help coordinate a wider and more effective response to the HIV epidemic in South Africa.

  17. Oxidative Stress Predicts All-Cause Mortality in HIV-Infected Patients.

    Directory of Open Access Journals (Sweden)

    Mar Masiá

    Full Text Available We aimed to assess whether oxidative stress is a predictor of mortality in HIV-infected patients.We conducted a nested case-control study in CoRIS, a contemporary, multicentre cohort of HIV-infected patients, antiretroviral-naïve at entry, launched in 2004. Cases were patients who died with available stored plasma samples collected. Two age and sex-matched controls for each case were selected. We measured F2-isoprostanes (F2-IsoPs and malondialdehyde (MDA plasma levels in the first blood sample obtained after cohort engagement.54 cases and 93 controls were included. Median F2-IsoPs and MDA levels were significantly higher in cases than in controls. When adjustment was performed for age, HIV-transmission category, CD4 cell count and HIV viral load at cohort entry, and subclinical inflammation measured with highly-sensitive C-reactive protein (hsCRP, the association of F2-IsoPs with mortality remained significant (adjusted OR per 1 log10 increase, 2.34 [1.23-4.47], P = 0.009. The association of MDA with mortality was attenuated after adjustment: adjusted OR (95% CI per 1 log10 increase, 2.05 [0.91-4.59], P = 0.080. Median hsCRP was also higher in cases, and it also proved to be an independent predictor of mortality in the adjusted analysis: OR (95% CI per 1 log10 increase, 1.39 (1.01-1.91, P = 0.043; and OR (95% CI per 1 log10 increase, 1.46 (1.07-1.99, P = 0.014, respectively, when adjustment included F2-IsoPs and MDA.Oxidative stress is a predictor of all-cause mortality in HIV-infected patients. For plasma F2-IsoPs, this association is independent of HIV-related factors and subclinical inflammation.

  18. Evaluation of immune responses in HIV infected patients with pleural tuberculosis by the QuantiFERON® TB-Gold interferon-gamma assay

    Directory of Open Access Journals (Sweden)

    Lekabe Jacob M

    2008-03-01

    Full Text Available Abstract Background Diagnosis of tuberculous (TB pleuritis is difficult and better diagnostic tools are needed. New blood based interferon-gamma (IFN-γ tests are promising, but sensitivity could be low in HIV positive patients. The IFN-γ tests have not yet been validated for use in pleural fluid, a compartment with higher level of immune activation than in blood. Methods The QuantiFERON TB®-Gold (QFT-TB test was analysed in blood and pleural fluid from 34 patients presenting with clinically suspected pleural TB. Clinical data, HIV status and CD4 cell counts were recorded. Adenosine deaminase activity (ADA analysis and TB culture were performed on pleural fluid. Results The patients were categorised as 'confirmed TB' (n = 12, 'probable TB' (n = 16 and 'non-TB' pleuritis (n = 6 based on TB culture results and clinical and biochemical criteria. The majority of the TB patients were HIV infected (82%. The QFT-TB in pleural fluid was positive in 27% and 56% of the 'confirmed TB' and 'probable TB' cases, respectively, whereas the corresponding sensitivities in blood were 58% and 83%. Indeterminate results in blood (25% were caused by low phytohemagglutinin (PHA = positive control IFN-γ responses, significantly lower in the TB patients as compared to the 'non-TB' cases (p = 0.02. Blood PHA responses correlated with CD4 cell count (r = 0.600, p = 0.028. In contrast, in pleural fluid indeterminate results (52% were caused by high Nil (negative control IFN-γ responses in both TB groups. Still, the Nil IFN-γ responses were lower than the TB antigen responses (p Conclusion The QFT-TB test in blood could contribute to the diagnosis of TB pleuritis in the HIV positive population. Still, the number of inconclusive results is too high to recommend the commercial QFT-TB test for routine use in pleural fluid in a TB/HIV endemic resource-limited setting.

  19. [Computational prediction of human immunodeficiency resistance to reverse transcriptase inhibitors].

    Science.gov (United States)

    Tarasova, O A; Filimonov, D A; Poroikov, V V

    2017-10-01

    Human immunodeficiency virus (HIV) causes acquired immunodeficiency syndrome (AIDS) and leads to over one million of deaths annually. Highly active antiretroviral treatment (HAART) is a gold standard in the HIV/AIDS therapy. Nucleoside and non-nucleoside inhibitors of HIV reverse transcriptase (RT) are important component of HAART, but their effect depends on the HIV susceptibility/resistance. HIV resistance mainly occurs due to mutations leading to conformational changes in the three-dimensional structure of HIV RT. The aim of our work was to develop and test a computational method for prediction of HIV resistance associated with the mutations in HIV RT. Earlier we have developed a method for prediction of HIV type 1 (HIV-1) resistance; it is based on the usage of position-specific descriptors. These descriptors are generated using the particular amino acid residue and its position; the position of certain residue is determined in a multiple alignment. The training set consisted of more than 1900 sequences of HIV RT from the Stanford HIV Drug Resistance database; for these HIV RT variants experimental data on their resistance to ten inhibitors are presented. Balanced accuracy of prediction varies from 80% to 99% depending on the method of classification (support vector machine, Naive Bayes, random forest, convolutional neural networks) and the drug, resistance to which is obtained. Maximal balanced accuracy was obtained for prediction of resistance to zidovudine, stavudine, didanosine and efavirenz by the random forest classifier. Average accuracy of prediction is 89%.

  20. Multi-Sector Participation In The National Response To Prevent And Address The Hiv/Aids Epidemic In The Republic Of Cuba, 2007-2008

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    Isora Ramos Valle

    2010-12-01

    Full Text Available The development of a strong national response involving multiple sectors—including civil society—is an essential aspect of the social management of the HIV/AIDS epidemic. The goals of this response are to control the epidemic and improve the quality of life for people living with HIV/AIDS; this includes combating stigma and discrimination, as well as ensuring due compliance with the law. Cuba has a national program to prevent and control HIV/AIDS. Since 2003 Cuba’s national program has received material and financial support from the Global Fund to Fight AIDS, Tuberculosis and Malaria. Program evaluation is carried out by an independent team at ENSAP (National School of Public Health. This paper reports on results of one part of that evaluation: an assessment of the agencies and sectors who made up the organized social and national response to the HIV/AIDS epidemic. The evaluation primarily used qualitative analyses of the activities and tasks proposed by sectors in their 2006-2008 work plans. Visits were made to the provinces of Ciudad de la Habana, Matanzas, and Holguín. Qualitative techniques included in-depth interviews, semi-structured interviews, observation, and review of documentary evidence of all kinds (videos, reports, minutes, protocols, results of social research, and radio broadcast messages and varied depending on the particular features of each sector. We noted improvements in multi-sector participation in the prevention and response to the national HIV/AIDS epidemic. Conscious of their role, sectors generally carried out their programmed activities and had improved their organization, planning, and systematization; integration among the sectors was also better. These local initiatives provided evidence of a multi-sector response characterized by autonomy, emotional involvement, and an identification with the goals of the project; this went beyond simply meeting targets. Cross-sector work showed a marked increase and a

  1. Maternal nutritional status predicts adverse birth outcomes among HIV-infected rural Ugandan women receiving combination antiretroviral therapy.

    Directory of Open Access Journals (Sweden)

    Sera Young

    Full Text Available Maternal nutritional status is an important predictor of birth outcomes, yet little is known about the nutritional status of HIV-infected pregnant women treated with combination antiretroviral therapy (cART. We therefore examined the relationship between maternal BMI at study enrollment, gestational weight gain (GWG, and hemoglobin concentration (Hb among 166 women initiating cART in rural Uganda.Prospective cohort.HIV-infected, ART-naïve pregnant women were enrolled between 12 and 28 weeks gestation and treated with a protease inhibitor or non-nucleoside reverse transcriptase inhibitor-based combination regimen. Nutritional status was assessed monthly. Neonatal anthropometry was examined at birth. Outcomes were evaluated using multivariate analysis.Mean GWG was 0.17 kg/week, 14.6% of women experienced weight loss during pregnancy, and 44.9% were anemic. Adverse fetal outcomes included low birth weight (LBW (19.6%, preterm delivery (17.7%, fetal death (3.9%, stunting (21.1%, small-for-gestational age (15.1%, and head-sparing growth restriction (26%. No infants were HIV-infected. Gaining <0.1 kg/week was associated with LBW, preterm delivery, and a composite adverse obstetric/fetal outcome. Maternal weight at 7 months gestation predicted LBW. For each g/dL higher mean Hb, the odds of small-for-gestational age decreased by 52%.In our cohort of HIV-infected women initiating cART during pregnancy, grossly inadequate GWG was common. Infants whose mothers gained <0.1 kg/week were at increased risk for LBW, preterm delivery, and composite adverse birth outcomes. cART by itself may not be sufficient for decreasing the burden of adverse birth outcomes among HIV-infected women.Clinicaltrials.gov NCT00993031.

  2. 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.

  3. Analysis of HIV Diversity in HIV-Infected Black Men Who Have Sex with Men (HPTN 061.

    Directory of Open Access Journals (Sweden)

    Iris Chen

    Full Text Available HIV populations often diversify in response to selective pressures, such as the immune response and antiretroviral drug use. We analyzed HIV diversity in Black men who have sex with men who were enrolled in the HIV Prevention Trials Network 061 study.A high resolution melting (HRM diversity assay was used to measure diversity in six regions of the HIV genome: two in gag, one in pol, and three in env. HIV diversity was analyzed for 146 men who were HIV infected at study enrollment, including three with acute infection and 13 with recent infection (identified using a multi-assay algorithm, and for 21 men who seroconverted during the study. HIV diversification was analyzed in a paired analysis for 62 HIV-infected men using plasma samples from the enrollment and 12-month (end of study visits.Men with acute or recent infection at enrollment and seroconverters had lower median HRM scores (lower HIV diversity than men with non-recent infection in all six regions analyzed. In univariate analyses, younger age, higher CD4 cell count, and HIV drug resistance were associated with lower median HRM scores in multiple regions; ARV drug detection was marginally associated with lower diversity in the pol region. In multivariate analysis, acute or recent infection (all six regions and HIV drug resistance (both gag regions were associated with lower median HRM scores. Diversification in the pol region over 12 months was greater for men with acute or recent infection, higher CD4 cell count, and lower HIV viral load at study enrollment.HIV diversity was significantly associated with duration of HIV infection, and lower gag diversity was observed in men who had HIV drug resistance. HIV pol diversification was more pronounced in men with acute or recent infection, higher CD4 cell count, and lower HIV viral load.

  4. [Analysis on funds application of community based organizations involved in HIV/AIDS response and government financial investment in China, 2014].

    Science.gov (United States)

    Zhang, G; Zhu, Y X; Wang, P; Liu, P; Li, J F; Sha, S; Yang, W Z; Li, H

    2017-03-06

    Objective: To understand the government financial investments to community based organizations (CBO) involved in HIV/AIDS Control and Prevention of China and its influencing factors. Methods: Questionnaire of the situation of CBO involved in HIV/AIDS control and prevention were designed, and filled by the staff of Provincial Health Administrative Departments of 31 provinces (autonomous regions and municipalities). The research focused on the fields of CBO involved in HIV/AIDS response in 31 provinces (autonomous regions and municipalities), including intervention on HIV/AIDS high risk population (female sex worker (FSW), man who sex with man (MSM), drug user (DU) and case management and care for people living with HIV/AIDS (PLWH)). 29 valid questionnaires were collecting, with Shanxi Province and Inner Mongolia Autonomous Regions not filled. Questionnaire included financial supports from local governments, transfer payment from central government for CBO involved in HIV/AIDS response in 2014, and unit cost for CBO involved in HIV/AIDS control and prevention. Multivariate analysis was conducted on the project application and financial investment of community based organizations involved in HIV/AIDS control and prevention in 2014. Results: The total amount of CBO to apply for participation in AIDS prevention and control was 64 482 828 Yuan in 2014. The actual total amount of investment was 50 616 367 Yuan, The investment came from the central government funding, the provincial level government funding, the prefecture and county level government funding investment and other sources of funding. 22 of 28 provinces (autonomous regions and municipalities) received the funds from the central government finance, and median of investment funds 500 000 Yuan. 15 provinces (autonomous regions and municipalities) gained the funds from the provincial government finance, and median of investment funds 350 000 Yuan. 12 provinces (autonomous regions and municipalities) got the funds

  5. Immune Interventions to Eliminate the HIV Reservoir.

    Science.gov (United States)

    Hsu, Denise C; Ananworanich, Jintanat

    2017-10-26

    Inducing HIV remission is a monumental challenge. A potential strategy is the "kick and kill" approach where latently infected cells are first activated to express viral proteins and then eliminated through cytopathic effects of HIV or immune-mediated killing. However, pre-existing immune responses to HIV cannot eradicate HIV infection due to the presence of escape variants, inadequate magnitude, and breadth of responses as well as immune exhaustion. The two major approaches to boost immune-mediated elimination of infected cells include enhancing cytotoxic T lymphocyte mediated killing and harnessing antibodies to eliminate HIV. Specific strategies include increasing the magnitude and breadth of T cell responses through therapeutic vaccinations, reversing the effects of T cell exhaustion using immune checkpoint inhibition, employing bispecific T cell targeting immunomodulatory proteins or dual-affinity re-targeting molecules to direct cytotoxic T lymphocytes to virus-expressing cells and broadly neutralizing antibody infusions. Methods to steer immune responses to tissue sites where latently infected cells are located need to be further explored. Ultimately, strategies to induce HIV remission must be tolerable, safe, and scalable in order to make a global impact.

  6. HIV Controllers Exhibit Enhanced Frequencies of Major Histocompatibility Complex Class II Tetramer+ Gag-Specific CD4+ T Cells in Chronic Clade C HIV-1 Infection.

    Science.gov (United States)

    Laher, Faatima; Ranasinghe, Srinika; Porichis, Filippos; Mewalal, Nikoshia; Pretorius, Karyn; Ismail, Nasreen; Buus, Søren; Stryhn, Anette; Carrington, Mary; Walker, Bruce D; Ndung'u, Thumbi; Ndhlovu, Zaza M

    2017-04-01

    Immune control of viral infections is heavily dependent on helper CD4 + T cell function. However, the understanding of the contribution of HIV-specific CD4 + T cell responses to immune protection against HIV-1, particularly in clade C infection, remains incomplete. Recently, major histocompatibility complex (MHC) class II tetramers have emerged as a powerful tool for interrogating antigen-specific CD4 + T cells without relying on effector functions. Here, we defined the MHC class II alleles for immunodominant Gag CD4 + T cell epitopes in clade C virus infection, constructed MHC class II tetramers, and then used these to define the magnitude, function, and relation to the viral load of HIV-specific CD4 + T cell responses in a cohort of untreated HIV clade C-infected persons. We observed significantly higher frequencies of MHC class II tetramer-positive CD4 + T cells in HIV controllers than progressors ( P = 0.0001), and these expanded Gag-specific CD4 + T cells in HIV controllers showed higher levels of expression of the cytolytic proteins granzymes A and B. Importantly, targeting of the immunodominant Gag41 peptide in the context of HLA class II DRB1*1101 was associated with HIV control ( r = -0.5, P = 0.02). These data identify an association between HIV-specific CD4 + T cell targeting of immunodominant Gag epitopes and immune control, particularly the contribution of a single class II MHC-peptide complex to the immune response against HIV-1 infection. Furthermore, these results highlight the advantage of the use of class II tetramers in evaluating HIV-specific CD4 + T cell responses in natural infections. IMPORTANCE Increasing evidence suggests that virus-specific CD4 + T cells contribute to the immune-mediated control of clade B HIV-1 infection, yet there remains a relative paucity of data regarding the role of HIV-specific CD4 + T cells in shaping adaptive immune responses in individuals infected with clade C, which is responsible for the majority of HIV

  7. HIV-1 transgenic rat CD4+ T cells develop decreased CD28 responsiveness and suboptimal Lck tyrosine dephosphorylation following activation

    International Nuclear Information System (INIS)

    Yadav, Anjana; Pati, Shibani; Nyugen, Anhthu; Barabitskaja, Oxana; Mondal, Prosanta; Anderson, Michael; Gallo, Robert C.; Huso, David L.; Reid, William

    2006-01-01

    Impaired CD4+ T cell responses, resulting in dysregulated T-helper 1 (Th1) effector and memory responses, are a common result of HIV-1 infection. These defects are often preceded by decreased expression and function of the α/β T cell receptor (TCR)-CD3 complex and of co-stimulatory molecules including CD28, resulting in altered T cell proliferation, cytokine secretion and cell survival. We have previously shown that HIV Tg rats have defective development of T cell effector function and generation of specific effector/memory T cell subsets. Here we identify abnormalities in activated HIV-1 Tg rat CD4+ T cells that include decreased pY505 dephosphorylation of Lck (required for Lck activation), decreased CD28 function, reduced expression of the anti-apoptotic molecule Bcl-xL, decreased secretion of the mitogenic lympokine interleukin-2 (IL-2) and increased activation induced apoptosis. These events likely lead to defects in antigen-specific signaling and may help explain the disruption of Th1 responses and the generation of specific effector/memory subsets in transgenic CD4+ T cells

  8. Future-oriented tweets predict lower county-level HIV prevalence in the United States.

    Science.gov (United States)

    Ireland, Molly E; Schwartz, H Andrew; Chen, Qijia; Ungar, Lyle H; Albarracín, Dolores

    2015-12-01

    Future orientation promotes health and well-being at the individual level. Computerized text analysis of a dataset encompassing billions of words used across the United States on Twitter tested whether community-level rates of future-oriented messages correlated with lower human immunodeficiency virus (HIV) rates and moderated the association between behavioral risk indicators and HIV. Over 150 million tweets mapped to U.S. counties were analyzed using 2 methods of text analysis. First, county-level HIV rates (cases per 100,000) were regressed on aggregate usage of future-oriented language (e.g., will, gonna). A second data-driven method regressed HIV rates on individual words and phrases. Results showed that counties with higher rates of future tense on Twitter had fewer HIV cases, independent of strong structural predictors of HIV such as population density. Future-oriented messages also appeared to buffer health risk: Sexually transmitted infection rates and references to risky behavior on Twitter were associated with higher HIV prevalence in all counties except those with high rates of future orientation. Data-driven analyses likewise showed that words and phrases referencing the future (e.g., tomorrow, would be) correlated with lower HIV prevalence. Integrating big data approaches to text analysis and epidemiology with psychological theory may provide an inexpensive, real-time method of anticipating outbreaks of HIV and etiologically similar diseases. (PsycINFO Database Record (c) 2015 APA, all rights reserved).

  9. Ranitidine improves certain cellular immune responses in asymptomatic HIV-infected individuals

    DEFF Research Database (Denmark)

    Nielsøn, H J; Svenningsen, A; Moesgaard, F

    1991-01-01

    Human immunodeficiency virus (HIV) infection is characterized by a progressive impairment in immunocompetence leading to severe opportunistic infections and malignancies. In a double-blind, placebo-controlled study, the potential impact of immunomodulation by oral ranitidine, 600 mg daily, for 28...... days was studied in 18 HIV-positive patients (CDC group II). All were without clinical signs of infections and were not treated with other known immunomodulating agents. Several immunological parameters related to HIV infection were studied and confirmed to be impaired early in HIV infection...... shown in this study is small, the present result indicates the need for further trials with immunomodulation by ranitidine in HIV-infected individuals....

  10. 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.

    Directory of Open Access Journals (Sweden)

    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

  11. Chronic kidney disease in HIV patients

    Science.gov (United States)

    Bakri, S.; Rasyid, H.; Kasim, H.; Katu, S.

    2018-03-01

    Chronic kidney disease (CKD) is a health problem in human immunodeficiency virus (HIV) population. Prediction of CKD in HIV patients needsto have done. This study aimis to identify the prevalence of CKD in HIV patients.Thisis a cross-sectional studyofmale and female, age 18-60 years old, diagnosedHIVat Wahidin Sudirohusodo & Hasanuddin University Hospital Makassar. Diagnosed as CKD if estimated glomerular filtration rate (eGFR) HIV patients included in the analyses. Distribution of CKD, showed 3 (3.5%) subjects with eGFRHIV populations in Makassar is still quite low.

  12. Interactive Effects of Morphine on HIV Infection: Role in HIV-Associated Neurocognitive Disorder

    Directory of Open Access Journals (Sweden)

    Pichili Vijaya Bhaskar Reddy

    2012-01-01

    Full Text Available HIV epidemic continues to be a severe public health problem and concern within USA and across the globe with about 33 million people infected with HIV. The frequency of drug abuse among HIV infected patients is rapidly increasing and is another major issue since injection drug users are at a greater risk of developing HIV associated neurocognitive dysfunctions compared to non-drug users infected with HIV. Brain is a major target for many of the recreational drugs and HIV. Evidences suggest that opiate drug abuse is a risk factor in HIV infection, neural dysfunction and progression to AIDS. The information available on the role of morphine as a cofactor in the neuropathogenesis of HIV is scanty. This review summarizes the results that help in understanding the role of morphine use in HIV infection and neural dysfunction. Studies show that morphine enhances HIV-1 infection by suppressing IL-8, downregulating chemokines with reciprocal upregulation of HIV coreceptors. Morphine also activates MAPK signaling and downregulates cAMP response element-binding protein (CREB. Better understanding on the role of morphine in HIV infection and mechanisms through which morphine mediates its effects may help in devising novel therapeutic strategies against HIV-1 infection in opiate using HIV-infected population.

  13. Sex, college major, and attribution of responsibility in empathic responding to persons with HIV infection.

    Science.gov (United States)

    Bécares, Laia; Turner, Castellano

    2004-10-01

    This investigation studied the influence of sex, college major, and attributed responsibility on college students' empathic responding towards persons infected with HIV. We hypothesized that (1) women would score higher on empathy than men; (2) nursing and psychology majors would score higher on empathy than business and computer science majors; and (3) participants would score higher on empathy towards a target who contracted HIV through blood transfusion (presented as a Nonresponsible target) rather than through unprotected sex (presented as a Responsible target). Two hundred and fifty-eight undergraduate students (110 male, 148 female) attending a large urban university in the northeast filled out an anonymous demographic questionnaire, the Interpersonal Reactivity Index of Davis (1983), and an Empathy Reaction Scale that was developed by the authors. Results indicated a higher mean Empathy Reaction score from nursing and psychology students as compared to business and computer science students. There was no difference in Empathy Reaction scores between men and women. A higher Empathy Reaction score was found among participants who had read a diary from the target portrayed as Nonresponsible, as opposed to those who read a diary from the target portrayed as Responsible.

  14. HIV disclosure and stigma among women living with HIV in Denmark

    DEFF Research Database (Denmark)

    Wessman, Maria; Thorsteinsson, Kristina; Storgaard, Merete

    2017-01-01

    OBJECTIVE: To identify disclosure, stigma and predictors of non-disclosure among women living with HIV in Denmark. METHODS: A questionnaire study of women living with HIV in Denmark was performed. The enrolment period was from February 2013 to March 2014. Logistic regression was used to estimate......%), friends (63%) and children (41%). The primary reason for non-disclosure was a feeling that it did not concern others (55%), although reactions upon disclosure were mainly positive in 53%. Predictors of non-disclosure were being of black or Asian ethnicity. Following their HIV diagnosis, 40% no longer...... diagnosis to fewer than three people and black or Asian ethnicity predicted non-disclosure. HIV-related stigma regarding sex and contact with others is still highly prevalent; however, reactions to disclosure were mainly positive and associated with secondary positive gains. We strongly urge healthcare...

  15. Impact of the Hayflick Limit on T cell responses to infection: lessons from aging and HIV disease.

    Science.gov (United States)

    Effros, Rita B

    2004-02-01

    Aging and HIV disease show certain immunological similarities. In both situations, control over viral infection is diminished, and there is an increase in certain types of cancer. The immune cell type responsible for controlling viral infections and cancer is the so-called CD8 or cytotoxic T cell. In elderly persons and individuals chronically infected with HIV, there are high proportions of CD8 T cells that resemble cells that reach the end stage of replicative senescence in cell culture after repeated rounds of antigen-driven proliferation. Senescent cultures are characterized by irreversible cell cycle arrest, shortened telomeres, inability to upregulate telomerase, loss of CD28 expression, and apoptosis resistance. Strategies that retard replicative senescence may, therefore, provide novel approaches to enhancing immune function during aging and HIV disease.

  16. Verification Techniques for Parameter Selection and Bayesian Model Calibration Presented for an HIV Model

    Science.gov (United States)

    Wentworth, Mami Tonoe

    Uncertainty quantification plays an important role when making predictive estimates of model responses. In this context, uncertainty quantification is defined as quantifying and reducing uncertainties, and the objective is to quantify uncertainties in parameter, model and measurements, and propagate the uncertainties through the model, so that one can make a predictive estimate with quantified uncertainties. Two of the aspects of uncertainty quantification that must be performed prior to propagating uncertainties are model calibration and parameter selection. There are several efficient techniques for these processes; however, the accuracy of these methods are often not verified. This is the motivation for our work, and in this dissertation, we present and illustrate verification frameworks for model calibration and parameter selection in the context of biological and physical models. First, HIV models, developed and improved by [2, 3, 8], describe the viral infection dynamics of an HIV disease. These are also used to make predictive estimates of viral loads and T-cell counts and to construct an optimal control for drug therapy. Estimating input parameters is an essential step prior to uncertainty quantification. However, not all the parameters are identifiable, implying that they cannot be uniquely determined by the observations. These unidentifiable parameters can be partially removed by performing parameter selection, a process in which parameters that have minimal impacts on the model response are determined. We provide verification techniques for Bayesian model calibration and parameter selection for an HIV model. As an example of a physical model, we employ a heat model with experimental measurements presented in [10]. A steady-state heat model represents a prototypical behavior for heat conduction and diffusion process involved in a thermal-hydraulic model, which is a part of nuclear reactor models. We employ this simple heat model to illustrate verification

  17. A DNA vaccine encoding multiple HIV CD4 epitopes elicits vigorous polyfunctional, long-lived CD4+ and CD8+ T cell responses.

    Directory of Open Access Journals (Sweden)

    Daniela Santoro Rosa

    Full Text Available T-cell based vaccines against HIV have the goal of limiting both transmission and disease progression by inducing broad and functionally relevant T cell responses. Moreover, polyfunctional and long-lived specific memory T cells have been associated to vaccine-induced protection. CD4(+ T cells are important for the generation and maintenance of functional CD8(+ cytotoxic T cells. We have recently developed a DNA vaccine encoding 18 conserved multiple HLA-DR-binding HIV-1 CD4 epitopes (HIVBr18, capable of eliciting broad CD4(+ T cell responses in multiple HLA class II transgenic mice. Here, we evaluated the breadth and functional profile of HIVBr18-induced immune responses in BALB/c mice. Immunized mice displayed high-magnitude, broad CD4(+/CD8(+ T cell responses, and 8/18 vaccine-encoded peptides were recognized. In addition, HIVBr18 immunization was able to induce polyfunctional CD4(+ and CD8(+ T cells that proliferate and produce any two cytokines (IFNγ/TNFα, IFNγ/IL-2 or TNFα/IL-2 simultaneously in response to HIV-1 peptides. For CD4(+ T cells exclusively, we also detected cells that proliferate and produce all three tested cytokines simultaneously (IFNγ/TNFα/IL-2. The vaccine also generated long-lived central and effector memory CD4(+ T cells, a desirable feature for T-cell based vaccines. By virtue of inducing broad, polyfunctional and long-lived T cell responses against conserved CD4(+ T cell epitopes, combined administration of this vaccine concept may provide sustained help for CD8(+ T cells and antibody responses- elicited by other HIV immunogens.

  18. Risk factors for increased immune reconstitution in response to Mycobacterium tuberculosis antigens in tuberculosis HIV-infected, antiretroviral-naïve patients.

    Science.gov (United States)

    da Silva, Tatiana Pereira; Giacoia-Gripp, Carmem Beatriz Wagner; Schmaltz, Carolina A; Sant'Anna, Flavia Marinho; Saad, Maria Helena; Matos, Juliana Arruda de; de Lima E Silva, Julio Castro Alves; Rolla, Valeria Cavalcanti; Morgado, Mariza Gonçalves

    2017-09-06

    Little is known regarding the restoration of the specific immune response after combined antiretroviral therapy (cART) and anti-tuberculosis (TB) therapy introduction among TB-HIV patients. In this study, we examined the immune response of TB-HIV patients to Mycobacterium tuberculosis (Mtb) antigens to evaluate the response dynamics to different antigens over time. Moreover, we also evaluated the influence of two different doses of efavirenz and the factors associated with immune reconstitution. This is a longitudinal study nested in a clinical trial, where cART was initiated during the baseline visit (D0), which occurred 30 ± 10 days after the introduction of anti-TB therapy. Follow-up visits were performed at 30, 60, 90 and 180 days after cART initiation. The production of IFN-γ upon in vitro stimulation with Mtb antigens purified protein derivative (PPD), ESAT-6 and 38 kDa/CFP-10 using ELISpot was examined at baseline and follow-up visits. Sixty-one patients, all ART-naïve, were selected and included in the immune reconstitution analysis; seven (11.5%) developed Immune Reconstitution Inflammatory Syndrome (IRIS). The Mtb specific immune response was higher for the PPD antigen followed by 38 kDa/CFP-10 and increased in the first 60 days after cART initiation. In multivariate analysis, the variables independently associated with increased IFN-γ production in response to PPD antigen were CD4 + T cell counts tuberculosis, 800 mg efavirenz dose and follow-up CD4 + T cell counts. Moreover, the factors associated with the production of IFN-γ in response to 38 kDa/CFP-10 were detectable HIV viral load (VL) and CD4 + T cell counts at follow-up visits of ≥200 cells/mm 3 . These findings highlight the differences in immune response according to the specificity of the Mtb antigen, which contributes to a better understanding of TB-HIV immunopathogenesis. IFN-γ production elicited by PPD and 38 kDa/CFP-10 antigens have a greater magnitude compared to ESAT-6

  19. Living with HIV: Patients Perspective

    Centers for Disease Control (CDC) Podcasts

    This podcast showcases three people who are living with HIV. The patients share their experiences of being diagnosed with HIV, of the treatments they are undergoing, and on taking responsibility for their health.

  20. 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.

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

    Science.gov (United States)

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

    2017-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Yonas Bekele

    2018-01-01

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

  3. 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

  4. HIV subtype influences HLA-B*07:02-associated HIV disease outcome

    DEFF Research Database (Denmark)

    Kløverpris, Henrik N; Adland, Emily; Koyanagi, Madoka

    2014-01-01

    Genetic polymorphisms within the MHC encoding region have the strongest impact on HIV disease progression of any in the human genome and provide important clues to the mechanisms of HIV immune control. Few analyses have been undertaken of HLA alleles associated with rapid disease progression. HLA......% versus 43% in HLA-B*07:02-negative subjects). These data support earlier studies suggesting that increased breadth of the Gag-specific CD8(+) T cell response may contribute to improved HIV immune control irrespective of the particular HLA molecules expressed....

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

    Science.gov (United States)

    2018-01-01

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

  6. HIV-DNA Given with or without Intradermal Electroporation Is Safe and Highly Immunogenic in Healthy Swedish HIV-1 DNA/MVA Vaccinees: A Phase I Randomized Trial.

    Directory of Open Access Journals (Sweden)

    Charlotta Nilsson

    Full Text Available We compared safety and immunogenicity of intradermal (ID vaccination with and without electroporation (EP in a phase I randomized placebo-controlled trial of an HIV-DNA prime HIV-MVA boost vaccine in healthy Swedish volunteers.HIV-DNA plasmids encoding HIV-1 genes gp160 subtypes A, B and C; Rev B; Gag A and B and RTmut B were given ID at weeks 0, 6 and 12 in a dose of 0.6 mg. Twenty-five volunteers received vaccine using a needle-free device (ZetaJet with (n=16 or without (n=9 ID EP (Dermavax. Five volunteers were placebo recipients. Boosting with recombinant MVA-CMDR expressing HIV-1 Env, Gag, Pol of CRF01_AE (HIV-MVA or placebo was performed at weeks 24 and 40. Nine of the vaccinees received a subtype C CN54 gp140 protein boost together with HIV-MVA.The ID/EP delivery was very well tolerated. After three HIV-DNA immunizations, no statistically significant difference was seen in the IFN-γ ELISpot response rate to Gag between HIV-DNA ID/EP recipients (5/15, 33% and HIV-DNA ID recipients (1/7, 14%, p=0.6158. The first HIV-MVA or HIV-MVA+gp140 vaccination increased the IFN-γ ELISpot response rate to 18/19 (95%. CD4+ and/or CD8+ T cell responses to Gag or Env were demonstrable in 94% of vaccinees. A balanced CD4+ and CD8+ T cell response was noted, with 78% and 71% responders, respectively. IFN-γ and IL-2 dominated the CD4+ T cell response to Gag and Env. The CD8+ response to Gag was broader with expression of IFN-γ, IL-2, MIP-1β and/or CD107. No differences were seen between DNA vaccine groups. Binding antibodies were induced after the second HIV-MVA+/-gp140 in 93% of vaccinees to subtype C Env, with the highest titers among EP/gp140 recipients.Intradermal electroporation of HIV-DNA was well tolerated. Strong cell- and antibody-mediated immune responses were elicited by the HIV-DNA prime and HIV-MVA boosting regimen, with or without intradermal electroporation use.International Standard Randomised Controlled Trial Number (ISRCTN 60284968.

  7. HIV-DNA Given with or without Intradermal Electroporation Is Safe and Highly Immunogenic in Healthy Swedish HIV-1 DNA/MVA Vaccinees: A Phase I Randomized Trial.

    Science.gov (United States)

    Nilsson, Charlotta; Hejdeman, Bo; Godoy-Ramirez, Karina; Tecleab, Teghesti; Scarlatti, Gabriella; Bråve, Andreas; Earl, Patricia L; Stout, Richard R; Robb, Merlin L; Shattock, Robin J; Biberfeld, Gunnel; Sandström, Eric; Wahren, Britta

    2015-01-01

    We compared safety and immunogenicity of intradermal (ID) vaccination with and without electroporation (EP) in a phase I randomized placebo-controlled trial of an HIV-DNA prime HIV-MVA boost vaccine in healthy Swedish volunteers. HIV-DNA plasmids encoding HIV-1 genes gp160 subtypes A, B and C; Rev B; Gag A and B and RTmut B were given ID at weeks 0, 6 and 12 in a dose of 0.6 mg. Twenty-five volunteers received vaccine using a needle-free device (ZetaJet) with (n=16) or without (n=9) ID EP (Dermavax). Five volunteers were placebo recipients. Boosting with recombinant MVA-CMDR expressing HIV-1 Env, Gag, Pol of CRF01_AE (HIV-MVA) or placebo was performed at weeks 24 and 40. Nine of the vaccinees received a subtype C CN54 gp140 protein boost together with HIV-MVA. The ID/EP delivery was very well tolerated. After three HIV-DNA immunizations, no statistically significant difference was seen in the IFN-γ ELISpot response rate to Gag between HIV-DNA ID/EP recipients (5/15, 33%) and HIV-DNA ID recipients (1/7, 14%, p=0.6158). The first HIV-MVA or HIV-MVA+gp140 vaccination increased the IFN-γ ELISpot response rate to 18/19 (95%). CD4+ and/or CD8+ T cell responses to Gag or Env were demonstrable in 94% of vaccinees. A balanced CD4+ and CD8+ T cell response was noted, with 78% and 71% responders, respectively. IFN-γ and IL-2 dominated the CD4+ T cell response to Gag and Env. The CD8+ response to Gag was broader with expression of IFN-γ, IL-2, MIP-1β and/or CD107. No differences were seen between DNA vaccine groups. Binding antibodies were induced after the second HIV-MVA+/-gp140 in 93% of vaccinees to subtype C Env, with the highest titers among EP/gp140 recipients. Intradermal electroporation of HIV-DNA was well tolerated. Strong cell- and antibody-mediated immune responses were elicited by the HIV-DNA prime and HIV-MVA boosting regimen, with or without intradermal electroporation use. International Standard Randomised Controlled Trial Number (ISRCTN) 60284968.

  8. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... AIDS.gov : This blog fosters public discussions on using new media effectively in response to HIV/AIDS, as well as HIV/AIDS research and policies. AIDS.gov New Media Tools : These ...

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

    Science.gov (United States)

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

    2010-01-01

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

  10. Innate immune recognition and activation during HIV infection

    Directory of Open Access Journals (Sweden)

    Larsen Carsten S

    2010-06-01

    Full Text Available Abstract The pathogenesis of HIV infection, and in particular the development of immunodeficiency, remains incompletely understood. Whichever intricate molecular mechanisms are at play between HIV and the host, it is evident that the organism is incapable of restricting and eradicating the invading pathogen. Both innate and adaptive immune responses are raised, but they appear to be insufficient or too late to eliminate the virus. Moreover, the picture is complicated by the fact that the very same cells and responses aimed at eliminating the virus seem to play deleterious roles by driving ongoing immune activation and progressive immunodeficiency. Whereas much knowledge exists on the role of adaptive immunity during HIV infection, it has only recently been appreciated that the innate immune response also plays an important part in HIV pathogenesis. In this review, we present current knowledge on innate immune recognition and activation during HIV infection based on studies in cell culture, non-human primates, and HIV-infected individuals, and discuss the implications for the understanding of HIV immunopathogenesis.

  11. Wits University's response to HIV/AIDS: flagship programme or ...

    African Journals Online (AJOL)

    HIV/AIDS is a threat to the creation of human capital and development prospects in southern Africa and South Africa. The University of the Witwatersrand (Wits) is a well-regarded institution of higher education in Johannesburg. This paper outlines the university's qualified failure to implement its HIV/AIDS Policy through a ...

  12. The distribution of new HIV infections by mode of exposure in Morocco

    Science.gov (United States)

    Mumtaz, Ghina R; Kouyoumjian, Silva P; Hilmi, Nahla; Zidouh, Ahmed; Rhilani, Houssine El; Alami, Kamal; Bennani, Aziza; Gouws, Eleanor; Ghys, Peter Denis; Abu-Raddad, Laith J

    2013-01-01

    Objectives Building on a wealth of new empirical data, the objective of this study was to estimate the distribution of new HIV infections in Morocco by mode of exposure using the modes of transmission (MoT) mathematical model. Methods The MoT model was implemented within a collaboration with the Morocco Ministry of Health and the Joint United Nations Programme on HIV/AIDS. The model was parameterised through a comprehensive review and synthesis of HIV and risk behaviour data in Morocco, mainly through the Middle East and North Africa HIV/AIDS Synthesis Project. Uncertainty analyses were used to assess the reliability of and uncertainty around our calculated estimates. Results Female sex workers (FSWs), clients of FSWs, men who have sex with men (MSM) and injecting drug users (IDUs) contributed 14%, 24%, 14% and 7% of new HIV infections, respectively. Two-thirds (67%) of new HIV infections occurred among FSWs, clients of FSWs, MSM and IDUs, or among the stable sexual partners of these populations. Casual heterosexual sex contributed 7% of HIV infections. More than half (52%) of HIV incidence is among females, but 71% of these infections are due to an infected spouse. The vast majority of HIV infections among men (89%) are due to high-risk behaviour. A very small HIV incidence is predicted to arise from medical injections or blood transfusions (0.1%). Conclusions The HIV epidemic in Morocco is driven by HIV incidence in high-risk population groups, with commercial heterosexual sex being the largest contributor to incidence. There is a need to focus HIV response more on these populations, mainly through proactive and sustainable HIV surveillance, and the expansion and increased geographical coverage of services such as condom promotion among FSWs, voluntary counselling and testing, harm reduction and treatment. PMID:23413401

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

    Science.gov (United States)

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

    2017-10-01

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

  14. Male Circumcision for HIV Prevention in South Africa: Addressing HIV and Gender Relations

    OpenAIRE

    Fischer-Nielsen, Sara; Møller, Sabrah

    2011-01-01

    The thesis scrutinizes how gender relations and women’s and men’s control of sexual health are influenced by the intervention of male circumcision for HIV prevention in South Africa. The analytical framework combines the theory of therapeutic citizenship, post-development theory and gender theory. We argue that the individual man’s choice to circumcise is being challenged by international HIV prevention methods emphasizing men’s responsibility in HIV prevention. In South Africa, current chang...

  15. Evaluation of four rapid tests for diagnosis and differentiation of HIV-1 and HIV-2 infections in Guinea-Conakry, West Africa.

    OpenAIRE

    Chaillet, Pascale; Tayler-Smith, Katie; Zachariah, Rony; Duclos, Nanfack; Moctar, Diallo; Beelaert, Greet; Fransen, Katrien

    2010-01-01

    With both HIV-1 and HV-2 prevalent in Guinea-Conakry, accurate diagnosis and differentiation is crucial for treatment purposes. Thus, four rapid HIV tests were evaluated for their HIV-1 and HIV-2 diagnostic and discriminative capacity for use in Guinea-Conakry. These included SD Bioline HIV 1/2 3.0 (Standard Diagnostics Inc.), Genie II HIV1/HIV2 (Bio-Rad), First Response HIV Card Test 1-2.0 (PMC Medical) and Immunoflow HIV1-HIV2 (Core Diagnostics). Results were compared with gold standard tes...

  16. Heterologous prime-boost regimens with a recombinant chimpanzee adenoviral vector and adjuvanted F4 protein elicit polyfunctional HIV-1-specific T-Cell responses in macaques.

    Science.gov (United States)

    Lorin, Clarisse; Vanloubbeeck, Yannick; Baudart, Sébastien; Ska, Michaël; Bayat, Babak; Brauers, Geoffroy; Clarinval, Géraldine; Donner, Marie-Noëlle; Marchand, Martine; Koutsoukos, Marguerite; Mettens, Pascal; Cohen, Joe; Voss, Gerald

    2015-01-01

    HIV-1-specific CD4+ and CD8+ T lymphocytes are important for HIV-1 replication control. F4/AS01 consists of F4 recombinant fusion protein (containing clade B Gag/p24, Pol/RT, Nef and Gag/p17) formulated in AS01 Adjuvant System, and was shown to induce F4-specific polyfunctional CD4+ T-cell responses in humans. While replication-incompetent recombinant HIV-1/SIV antigen-expressing human adenoviral vectors can elicit high-frequency antigen-specific CD8+ T-cell responses, their use is hampered by widespread pre-existing immunity to human serotypes. Non-human adenovirus serotypes associated with lower prevalence may offer an alternative strategy. We evaluated the immunogenicity of AdC7-GRN ('A'), a recombinant chimpanzee adenovirus type 7 vector expressing clade B Gag, RT and Nef, and F4/AS01 ('P'), when delivered intramuscularly in homologous (PP or AA) and heterologous (AAPP or PPAA) prime-boost regimens, in macaques and mice. Vaccine-induced HIV-1-antigen-specific T cells in peripheral blood (macaques), liver, spleen, and intestinal and genital mucosa (mice) were characterized by intracellular cytokine staining. Vaccine-specific IgG antibodies (macaques) were detected using ELISA. In macaques, only the heterologous prime-boost regimens induced polyfunctional, persistent and balanced CD4+ and CD8+ T-cell responses specific to each HIV-1 vaccine antigen. AdC7-GRN priming increased the polyfunctionality of F4/AS01-induced CD4+ T cells. Approximately 50% of AdC7-GRN-induced memory CD8+ T cells exhibited an effector-memory phenotype. HIV-1-specific antibodies were detected with each regimen. In mice, antigen-specific CD4+ and CD8+ T-cell responses were detected in the mucosal and systemic anatomical compartments assessed. When administered in heterologous prime-boost regimens, AdC7-GRN and F4/AS01 candidate vaccines acted complementarily in inducing potent and persistent peripheral blood HIV-1-specific CD4+ and CD8+ T-cell responses and antibodies in macaques. Besides

  17. CD4 cell count response to first-line combination ART in HIV-2+ patients compared with HIV-1+ patients

    DEFF Research Database (Denmark)

    Wittkop, Linda; Arsandaux, Julie; Trevino, Ana

    2017-01-01

    Background: CD4 cell recovery following first-line combination ART (cART) is poorer in HIV-2+ than in HIV-1+ patients. Only large comparisons may allow adjustments for demographic and pretreatment plasma viral load (pVL). Methods: ART-naive HIV+ adults from two European multicohort collaborations...

  18. Oral complications of HIV disease

    Directory of Open Access Journals (Sweden)

    Jair C. Leao

    2009-05-01

    Full Text Available Oral lesions are among the early signs of HIV infection and can predict its progression to acquired immunodeficiency syndrome (AIDS. A better understanding of the oral manifestations of AIDS in both adults and children has implications for all health care professionals. The knowledge of such alterations would allow for early recognition of HIV-infected patients. The present paper reviews epidemiology, relevant aspects of HIV infection related to the mouth in both adults and children, as well as current trends in antiretroviral therapy and its connection with orofacial manifestations related to AIDS.

  19. Effect of abacavir on sustained virologic response to HCV treatment in HIV/HCV co-infected patients, Cohere in Eurocoord

    DEFF Research Database (Denmark)

    Smit, Colette; Arends, Joop; Peters, Lars

    2015-01-01

    BACKGROUND: Contradicting results on the effect of abacavir (ABC) on hepatitis C virus (HCV) treatment responses in HIV/HCV co-infected patients have been reported. We evaluated the influence of ABC on the response to pegylated interferon (pegIFN) and ribavirin (RBV)-containing HCV treatment in H...

  20. Regulation of oxidative stress in response to acute aerobic and resistance exercise in HIV-infected subjects: a case-control study.

    Science.gov (United States)

    Deresz, L F; Sprinz, E; Kramer, A S; Cunha, G; de Oliveira, A R; Sporleder, H; de Freitas, D R J; Lazzarotto, A R; Dall'Ago, P

    2010-11-01

    Human immunodeficiency virus (HIV)-infected subjects have increased levels of oxidative stress which could impair immunological function and therefore contribute to the progression of AIDS. These characteristics are usually evaluated at rest and responses to exercise have yet to be evaluated. The aim of the present study was to assess the effect of a bout of aerobic exercise followed by resistance exercises on antioxidant system in HIV-infected and non-HIV subjects. There were included 14 cases (HIV-positive) and 14 controls (HIV-negative). The exercise protocol consisted of a single session of 20 minutes on a cycloergometer followed by a set of six resistance exercises. The activity of glutathione S-transferase (GST) and catalase were measured in plasma samples, total glutathione (TGSH) and thiobarbituric acid reactive substances (TBARS) were measured in erythrocytes. T CD4+ cells, T CD8+, viral load, complete blood count, and white blood count were also assessed. All measurements were performed at three times: baseline, after aerobic exercise, and after resistance exercises. At baseline, the HIV group had lower GST activity than controls, but after the exercise session GST values were similar in both groups. Compared to the control group TGSH was significantly lower in the HIV group at baseline, after aerobic and resistance exercises. The control group presented higher TBARS values after aerobic exercise compared to the HIV group. The neutrophil count was lower in the HIV group after aerobic and resistance exercises. These data indicate that HIV-infected subjects had lower antioxidant activity at rest. Physical exercise stimulated the enzymatic activity similarly in both groups.

  1. Prognostic value of immunologic abnormalities and HIV antigenemia in asymptomatic HIV-infected individuals: proposal of immunologic staging

    DEFF Research Database (Denmark)

    Hofmann, B; Bygbjerg, Ib Christian; Dickmeiss, E

    1989-01-01

    The prognostic value of various immunologic tests was investigated in 150 HIV-seropositive homosexual men, who were initially without HIV-related symptoms or AIDS and who were followed for a median of 12 months (range 3-28 months). The laboratory investigations included HIV antigen in serum, total...... lymphocyte count, T-helper (CD4) and T-cytotoxic/suppressor (CD8) counts, and lymphocyte transformation responses to the mitogens phytohemagglutinin (PHA) and pokeweed mitogen (PWM), and to antigenic extracts from Candida albicans and cytomegalovirus. 24 individuals developed HIV-related symptoms or AIDS (11...... cases). All parameters except the CD8 count were of prognostic value, but a multivariate analysis of symptom-free survival showed that HIV antigenemia, a CD4 count less than 0.5 x 10(9)/l, and relative response to PWM below 25% of controls contained all the prognostic information. Individuals abnormal...

  2. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... gov : This blog fosters public discussions on using new media effectively in response to HIV/AIDS, as ... as HIV/AIDS research and policies. AIDS.gov New Media Tools : These new media tools offer new ...

  3. Evidence of differential HLA class I-mediated viral evolution in functional and accessory/regulatory genes of HIV-1.

    Directory of Open Access Journals (Sweden)

    Zabrina L Brumme

    2007-07-01

    Full Text Available Despite the formidable mutational capacity and sequence diversity of HIV-1, evidence suggests that viral evolution in response to specific selective pressures follows generally predictable mutational pathways. Population-based analyses of clinically derived HIV sequences may be used to identify immune escape mutations in viral genes; however, prior attempts to identify such mutations have been complicated by the inability to discriminate active immune selection from virus founder effects. Furthermore, the association between mutations arising under in vivo immune selection and disease progression for highly variable pathogens such as HIV-1 remains incompletely understood. We applied a viral lineage-corrected analytical method to investigate HLA class I-associated sequence imprinting in HIV protease, reverse transcriptase (RT, Vpr, and Nef in a large cohort of chronically infected, antiretrovirally naïve individuals. A total of 478 unique HLA-associated polymorphisms were observed and organized into a series of "escape maps," which identify known and putative cytotoxic T lymphocyte (CTL epitopes under selection pressure in vivo. Our data indicate that pathways to immune escape are predictable based on host HLA class I profile, and that epitope anchor residues are not the preferred sites of CTL escape. Results reveal differential contributions of immune imprinting to viral gene diversity, with Nef exhibiting far greater evidence for HLA class I-mediated selection compared to other genes. Moreover, these data reveal a significant, dose-dependent inverse correlation between HLA-associated polymorphisms and HIV disease stage as estimated by CD4(+ T cell count. Identification of specific sites and patterns of HLA-associated polymorphisms across HIV protease, RT, Vpr, and Nef illuminates regions of the genes encoding these products under active immune selection pressure in vivo. The high density of HLA-associated polymorphisms in Nef compared to other

  4. The influence of bacterial vaginosis on the response to Trichomonas vaginalis treatment among HIV-infected women.

    Science.gov (United States)

    Gatski, Megan; Martin, David H; Levison, Judy; Mena, Leandro; Clark, Rebecca A; Murphy, Mary; Henderson, Harold; Schmidt, Norine; Kissinger, Patricia

    2011-04-01

    Trichomonas vaginalis (TV) is common in HIV+ women, and host factors may play a role in TV treatment outcomes. The purpose of this study was to examine the influence of bacterial vaginosis (BV) on the response to TV treatment among HIV+ women. A secondary analysis was conducted of a clinical trial which randomised HIV+/TV+ women to metronidazole (MTZ) treatment: 2 g (single-dose) versus 7 day 500 mg twice daily (multidose). BV was classified using Nugent scores from baseline Gram stains. Women were recultured for TV at test-of-cure (TOC) and again at 3 months if TV-negative at TOC. Repeat TV infection rates were compared for women with a baseline TV/BV coinfection versus baseline TV infection only, and stratified by treatment arm. Among 244 HIV+/TV+ women (mean age=40.3, ±9.5; 92.2% African-American), the rate of BV was 66.8%. Women with BV were more likely to report douching and ≥1 recent sex partners. HIV+ women with baseline TV/BV coinfection were more likely to be TV-positive at TOC than women with baseline TV infection only (RR 2.42 (95% CI 0.96 to 6.07; p=0.05)). When stratified by treatment arm, the association was only found in the single-dose arm (p=0.02) and not in the multidose arm (p=0.92). This interaction did not persist at 3 months. For HIV+/TV+ women, the rate of BV was high, and BV was associated with early failure of the MTZ single-dose treatment for TV. Biological explanations require further investigation.

  5. Predicting Arrest in a Sample of Youth Perinatally Exposed to HIV: The Intersection of HIV and Key Contextual Factors.

    Science.gov (United States)

    Elkington, Katherine S; Peters, Zachary; Choi, C Jean; Bucek, Amelia; Leu, Cheng-Shiun; Abrams, Elaine J; Mellins, Claude A

    2017-11-22

    We examined the role of youth HIV status and other key factors on past-year arrest in perinatally HIV-exposed but uninfected (PHIV-) and perinatally HIV-infected (PHIV+) youth using data from a multi-site study of psychosocial behaviors in PHIV-exposed urban youth (N = 340; 61% PHIV+; 51% female; ages 9-16 at baseline). Youth and caregivers were administered 5 interviews, spanning approximately 7.5 years. Using longitudinal logistic mixed-effect models, we explored the association between past year arrest, internal [e.g., substance use disorder (SUD)] and external (e.g., neighborhood arrest rates) contextual factors, and social-regulation processes (e.g., in-school/work). Arrest rates increased from 2.6 to 19.7% across follow-ups; there were no differences in arrest over time by HIV status. In the final model, odds of arrest were greater for youth who were male, with SUD, ≥ 18 years old, with high levels of city stress, and neither in school nor employed. PHIV-exposed, urban youth have much higher rates of arrest than national samples. Lack of differences in arrest by HIV status suggests key contextual factors are more important in promoting arrest.

  6. Prevalence and mortality of cancer among HIV-infected inpatients in Beijing, China.

    Science.gov (United States)

    Yang, Jun; Su, Shu; Zhao, Hongxin; Wang, Dennis; Wang, Jiali; Zhang, Fujie; Zhao, Yan

    2016-02-16

    Cancer is responsible for elevated HIV-related morbidity and mortality. Research on HIV-infected patients with concurrent cancer is rare in China. The purpose of our study was to investigate the prevalence and risk factors associated with cancer among HIV-infected inpatients in Beijing, and to investigate the mortality and risk factors among HIV-infected inpatients with cancer. Hospital records from a total of 1946 HIV-infected patients were collected from the Beijing Ditan Hospital. The data, from 2008 to 2013, were collected retrospectively. The cancer diagnoses included AIDS-defining cancers (ADC) and non-AIDS defining cancers (NADC). Logistic regression was used to identify risk factors predicting the concurrence of cancer with HIV. Mortality was examined using Kaplan-Meier estimates and Cox proportional hazards models. 7.7 % (149 cases) of all HIV-infected inpatients had concurrent cancer at their first hospital admission; of those, 33.6 % (50 cases) had ADCs, and 66.4 % (99 cases) had NADCs. The most prevalent NADCs were Hodgkin's lymphoma, gastrointestinal cancer, liver cancer, and lung cancer. Patients who did not accept antiretroviral therapy (ART) were more likely to suffer from cancer [AOR = 2.07 (1.42-3.01), p = 0.001]. Kaplan-Meier curves indicated that the survival probability of HIV-positive cancer patients was significantly lower than that of HIV-positive cancer-free patients (log-rank test, p cancer, the mortality was also higher among those who did not receive ART [AHR = 2.19 (1.84-2.61), p cancer concurrence among hospitalized HIV-infected patients was 7.7 %. Concurrent cancer also increased mortality among HIV-infected patients. ART was protective against concurrent cancer as well as mortality among HIV-infected cancer patients. These results highlight the importance of promoting cancer screening and early ART initiation among HIV-infected patients.

  7. National South African HIV prevalence estimates robust despite substantial test non-participation

    Directory of Open Access Journals (Sweden)

    Guy Harling

    2017-07-01

    Full Text Available Background. South African (SA national HIV seroprevalence estimates are of crucial policy relevance in the country, and for the worldwide HIV response. However, the most recent nationally representative HIV test survey in 2012 had 22% test non-participation, leaving the potential for substantial bias in current seroprevalence estimates, even after controlling for selection on observed factors. Objective. To re-estimate national HIV prevalence in SA, controlling for bias due to selection on both observed and unobserved factors in the 2012 SA National HIV Prevalence, Incidence and Behaviour Survey. Methods. We jointly estimated regression models for consent to test and HIV status in a Heckman-type bivariate probit framework. As selection variable, we used assigned interviewer identity, a variable known to predict consent but highly unlikely to be associated with interviewees’ HIV status. From these models, we estimated the HIV status of interviewed participants who did not test. Results. Of 26 710 interviewed participants who were invited to test for HIV, 21.3% of females and 24.3% of males declined. Interviewer identity was strongly correlated with consent to test for HIV; declining a test was weakly associated with HIV serostatus. Our HIV prevalence estimates were not significantly different from those using standard methods to control for bias due to selection on observed factors: 15.1% (95% confidence interval (CI 12.1 - 18.6 v. 14.5% (95% CI 12.8 - 16.3 for 15 - 49-year-old males; 23.3% (95% CI 21.7 - 25.8 v. 23.2% (95% CI 21.3 - 25.1 for 15 - 49-year-old females. Conclusion. The most recent SA HIV prevalence estimates are robust under the strongest available test for selection bias due to missing data. Our findings support the reliability of inferences drawn from such data.

  8. Novel engineered HIV-1 East African Clade-A gp160 plasmid construct induces strong humoral and cell-mediated immune responses in vivo

    International Nuclear Information System (INIS)

    Muthumani, Karuppiah; Zhang Donghui; Dayes, Nathanael S.; Hwang, Daniel S.; Calarota, Sandra A.; Choo, Andrew Y.; Boyer, Jean D.; Weiner, David B.

    2003-01-01

    HIV-1 sequences are highly diverse due to the inaccuracy of the viral reverse transcriptase. This diversity has been studied and used to categorize HIV isolates into subtypes or clades, which are geographically distinct. To develop effective vaccines against HIV-1, immunogens representing different subtypes may be important for induction of cross-protective immunity, but little data exist describing and comparing the immunogenicity induced by different subtype-based vaccines. This issue is further complicated by poor expression of HIV structural antigens due to rev dependence. One costly approach is to codon optimize each subtype construct to be examined. Interestingly, cis-acting transcriptional elements (CTE) can also by pass rev restriction by a rev independent export pathway. We reasoned that rev+CTE constructs might have advantages for such expression studies. A subtype A envelope sequence from a viral isolate from east Africa was cloned into a eukaryotic expression vector under the control of the CMV-IE promoter. The utility of inclusion of the Mason-Pfizer monkey virus (MPV)-CTE with/without rev for driving envelope expression and immunogenicity was examined. Expression of envelope (gp120) was confirmed by immunoblot analysis and by pseudotype virus infectivity assays. The presence of rev and the CTE together increased envelope expression and viral infection. Furthermore the CTE+rev construct was significantly more immunogenic then CTE alone vector. Isotype analysis and cytokine profiles showed strong Th1 response in plasmid-immunized mice, which also demonstrated the superior nature of the rev+CTE construct. These responses were of similar or greater magnitude to a codon-optimized construct. The resulting cellular immune responses were highly cross-reactive with a HIV-1 envelope subtype B antigen. This study suggests a simple strategy for improving the expression and immunogenicity of HIV subtype-specific envelope antigens as plasmid or vector

  9. HIV-1 and HIV-2 infections in Guinea-Bissau, West Africa : studies of immune responses, prevailing viruses and epidemiological trends

    OpenAIRE

    Andersson, Sören

    1999-01-01

    This thesis encompasses immunological, virological and epidemiological studies of HIV-1 and HIV-2 infections in Guinea-Bissau. We have established a robust and reliable diagnostic strategy based on a combination of enzyme-linked immunosorbent assays (ELISAs) and rapid simple tests. Evaluations showed that the strategy had a high capacity to discriminate between HIV-1 and HIV-2 and a high concordance with polymerase chain reaction (PCR) testing. Epidemiological studies in...

  10. Predicting response to epigenetic therapy

    DEFF Research Database (Denmark)

    Treppendahl, Marianne B; Sommer Kristensen, Lasse; Grønbæk, Kirsten

    2014-01-01

    of good pretreatment predictors of response is of great value. Many clinical parameters and molecular targets have been tested in preclinical and clinical studies with varying results, leaving room for optimization. Here we provide an overview of markers that may predict the efficacy of FDA- and EMA...

  11. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... gov : This blog fosters public discussions on using new media effectively in response to HIV/AIDS, as well as HIV/AIDS research and policies. AIDS.gov New Media Tools : These new media tools offer new ways ...

  12. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... home page . blog.AIDS.gov : This blog fosters public discussions on using new media effectively in response to HIV/AIDS, as well as HIV/AIDS research and policies. AIDS.gov New Media Tools : These new media ...

  13. Discordant HIV Test Results: Implications on Perinatal and Haemotransfusion Screening for HIV Infection, Cape Coast, Ghana.

    Science.gov (United States)

    Tetteh, Ato Kwamena; Agyarko, Edward

    2017-01-01

    Screening results of 488 pregnant women aged 15-44 years whose blood samples had been tested on-site, using First Response® HIV 1/2, and confirmed with INNO-LIA™ HIV I/II Score were used. Of this total, 178 were reactive (HIV I, 154; HIV II, 2; and HIV I and HIV II, 22). Of the 154 HIV I-reactive samples, 104 were confirmed to be HIV I-positive and 2 were confirmed to be HIV II-positive, while 48 were confirmed to be negative [false positive rate = 17.44% (13.56-21.32)]. The two HIV II samples submitted were confirmed to be negative with the confirmatory test. For the 22 HIV I and HIV II samples, 7 were confirmed to be HIV I-positive and 1 was confirmed to be HIV I- and HIV II-positive, while 14 were confirmed to be negative. Of the 310 nonreactive samples, 6 were confirmed to be HIV I-positive and 1 was confirmed to be HIV II-positive [false negative rate = 5.79% (1.63-8.38)], while 303 were negative. False negative outcomes will remain unconfirmed, with no management options for the client. False negative rate of 5.79% requires attention, as its resultant implications on control of HIV/AIDS could be dire.

  14. Testing and testing positive: childhood adversities and later life HIV status among Kenyan women and their partners.

    Science.gov (United States)

    Goodman, Michael L; Raimer-Goodman, Lauren; Chen, Catherine X; Grouls, Astrid; Gitari, Stanley; Keiser, Philip H

    2017-12-01

    Adverse childhood experiences are a critical feature of lifelong health. No research assesses whether childhood adversities predict HIV-testing behaviors, and little research analyzes childhood adversities and later life HIV status in sub-Saharan Africa. We use regression models with cross-sectional data from a representative sample (n = 1974) to analyze whether adverse childhood experiences, separately or as cumulative exposures, predict reports of later life HIV testing and testing HIV+ among semi-rural Kenyan women and their partners. No significant correlation was observed between thirteen cumulative childhood adversities and reporting prior HIV testing for respondent or partner. Separately, childhood sexual abuse and emotional neglect predicted lower odds of reporting having previously been tested for HIV. Witnessing household violence during one's childhood predicted significantly higher odds of reporting HIV+. Sexual abuse predicted higher odds of reporting a partner tested HIV+. Preventing sexual abuse and household violence may improve HIV testing and test outcomes among Kenyan women. More research is required to understand pathways between adverse childhood experiences and partner selection within Kenya and sub-Saharan Africa, and data presented here suggest understanding pathways may help improve HIV outcomes. © The Author 2016. Published by Oxford University Press on behalf of Faculty of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  15. Evolutionary genomics and HIV restriction factors.

    Science.gov (United States)

    Pyndiah, Nitisha; Telenti, Amalio; Rausell, Antonio

    2015-03-01

    To provide updated insights into innate antiviral immunity and highlight prototypical evolutionary features of well characterized HIV restriction factors. Recently, a new HIV restriction factor, Myxovirus resistance 2, has been discovered and the region/residue responsible for its activity identified using an evolutionary approach. Furthermore, IFI16, an innate immunity protein known to sense several viruses, has been shown to contribute to the defense to HIV-1 by causing cell death upon sensing HIV-1 DNA. Restriction factors against HIV show characteristic signatures of positive selection. Different patterns of accelerated sequence evolution can distinguish antiviral strategies--offense or defence--as well as the level of specificity of the antiviral properties. Sequence analysis of primate orthologs of restriction factors serves to localize functional domains and sites responsible for antiviral action. We use recent discoveries to illustrate how evolutionary genomic analyses help identify new antiviral genes and their mechanisms of action.

  16. Prevalence of Vitamin B12 and folic acid deficiency in HIV-positive patients and its association with neuropsychiatric symptoms and immunological response.

    Science.gov (United States)

    Adhikari, Prabha M R; Chowta, Mukta N; Ramapuram, John T; Rao, Satish; Udupa, Karthik; Acharya, Sahana Devdas

    2016-01-01

    Deficiency of micronutrients is prevalent even before the development of symptoms of HIV disease and is associated with accelerated HIV disease progression. This study evaluates the prevalence of folate and Vitamin B 12 deficiency in HIV-positive patients with or without tuberculosis (TB) and its association with neuropsychiatric symptoms and immunological response. Cross-sectional, observational study in an outpatient setting. Four groups of HIV-positive patients with TB (Group I), HIV-positive patients with neuropsychiatric symptoms (Group II), HIV-positive patients without neuropsychiatric symptoms or TB (Group III), and HIV-negative controls with neuropsychiatric symptoms (Group IV). Vitamin B 12 and folate estimation was done using carbonyl metallo-immunoassay method. ANOVA, Kruskal-Wallis and Mann-Whitney, Pearson's correlation. The prevalence of folic acid deficiency was 27.1% in the Group I, 31.9% in the Group II, 23.4% in the Group III, and 32% in the Group IV being higher in patients with neuropsychiatric symptoms in both HIV and non-HIV patients. The prevalence of Vitamin B 12 deficiency was 18.8% in Group I, 9.1% in Group II, 4.8% in Group III, and 16.7% in Group IV. The patients with folate deficiency had more severe depression and anxiety. Nearly, 30% of the HIV patients had a folic acid deficiency, and about 10% of the HIV patients had Vitamin B 12 deficiency. The folate deficiency was highest among neuropsychiatric patients with or without HIV infection and Vitamin B 12 deficiency was higher among HIV patients with TB.

  17. Association of Neisseria gonorrhoeae Opa(CEA with dendritic cells suppresses their ability to elicit an HIV-1-specific T cell memory response.

    Directory of Open Access Journals (Sweden)

    Qigui Yu

    Full Text Available Infection with Neisseria gonorrhoeae (N. gonorrhoeae can trigger an intense local inflammatory response at the site of infection, yet there is little specific immune response or development of immune memory. Gonococcal surface epitopes are known to undergo antigenic variation; however, this is unlikely to explain the weak immune response to infection since individuals can be re-infected by the same serotype. Previous studies have demonstrated that the colony opacity-associated (Opa proteins on the N. gonorrhoeae surface can bind human carcinoembryonic antigen-related cellular adhesion molecule 1 (CEACAM1 on CD4⁺ T cells to suppress T cell activation and proliferation. Interesting in this regard, N. gonorrhoeae infection is associated with impaired HIV-1 (human immunodeficiency virus type 1-specific cytotoxic T-lymphocyte (CTL responses and with transient increases in plasma viremia in HIV-1-infected patients, suggesting that N. gonorrhoeae may also subvert immune responses to co-pathogens. Since dendritic cells (DCs are professional antigen presenting cells (APCs that play a key role in the induction of an adaptive immune response, we investigated the effects of N. gonorrhoeae Opa proteins on human DC activation and function. While morphological changes reminiscent of DC maturation were evident upon N. gonorrhoeae infection, we observed a marked downregulation of DC maturation marker CD83 when the gonococci expressing CEACAM1-specific Opa(CEA, but not other Opa variants. Consistent with a gonococcal-induced defect in maturation, Opa(CEA binding to CEACAM1 reduced the DCs' capacity to stimulate an allogeneic T cell proliferative response. Moreover, Opa(CEA-expressing N. gonorrhoeae showed the potential to impair DC-dependent development of specific adaptive immunity, since infection with Opa(CEA-positive gonococci suppressed the ability of DCs to stimulate HIV-1-specific memory CTL responses. These results reveal a novel mechanism to explain

  18. HIV Genetic Diversity and Drug Resistance

    Science.gov (United States)

    Santos, André F.; Soares, Marcelo A.

    2010-01-01

    Most of the current knowledge on antiretroviral (ARV) drug development and resistance is based on the study of subtype B of HIV-1, which only accounts for 10% of the worldwide HIV infections. Cumulative evidence has emerged that different HIV types, groups and subtypes harbor distinct biological properties, including the response and susceptibility to ARV. Recent laboratory and clinical data highlighting such disparities are summarized in this review. Variations in drug susceptibility, in the emergence and selection of specific drug resistance mutations, in viral replicative capacity and in the dynamics of resistance acquisition under ARV selective pressure are discussed. Clinical responses to ARV therapy and associated confounding factors are also analyzed in the context of infections by distinct HIV genetic variants. PMID:21994646

  19. The HIV-1 envelope transmembrane domain binds TLR2 through a distinct dimerization motif and inhibits TLR2-mediated responses.

    Directory of Open Access Journals (Sweden)

    Eliran Moshe Reuven

    2014-08-01

    Full Text Available HIV-1 uses a number of means to manipulate the immune system, to avoid recognition and to highjack signaling pathways. HIV-1 infected cells show limited Toll-Like Receptor (TLR responsiveness via as yet unknown mechanisms. Using biochemical and biophysical approaches, we demonstrate that the trans-membrane domain (TMD of the HIV-1 envelope (ENV directly interacts with TLR2 TMD within the membrane milieu. This interaction attenuates TNFα, IL-6 and MCP-1 secretion in macrophages, induced by natural ligands of TLR2 both in in vitro and in vivo models. This was associated with decreased levels of ERK phosphorylation. Furthermore, mutagenesis demonstrated the importance of a conserved GxxxG motif in driving this interaction within the membrane milieu. The administration of the ENV TMD in vivo to lipotechoic acid (LTA/Galactosamine-mediated septic mice resulted in a significant decrease in mortality and in tissue damage, due to the weakening of systemic macrophage activation. Our findings suggest that the TMD of ENV is involved in modulation of the innate immune response during HIV infection. Furthermore, due to the high functional homology of viral ENV proteins this function may be a general character of viral-induced immune modulation.

  20. Routine antenatal HIV testing: the responses and perceptions of pregnant women and the viability of informed consent. A qualitative study.

    Science.gov (United States)

    de Zulueta, Paquita; Boulton, Mary

    2007-06-01

    This qualitative cross-sectional survey, undertaken in the antenatal booking clinics of a hospital in central London, explores pregnant women's responses to routine HIV testing, examines their reasons for declining or accepting the test, and assesses how far their responses fulfil standard criteria for informed consent. Of the 32 women interviewed, only 10 participants were prepared for HIV testing at their booking interview. None of the women viewed themselves as being particularly at risk for HIV infection. The minority (n = 6) of the participants who declined testing differed from those who accepted, by interpreting test acceptance as risky behaviour, privileging the negative outcomes of HIV positivity and expressing an inability to cope with these, should they occur. Troublingly, only a minority of women (n = 9) had a broad understanding of the rationale for the test, and none fulfilled the standard criteria for informed consent. This study suggests that, although routine screening combined with professional recommendation may be successful in increasing uptake, this may be at the cost of eroding informed consent. Protecting third parties (notably fetuses) from a preventable disease may outweigh the moral duty of respecting autonomy, enshrined in Western bioethical tradition. Nevertheless, such a policy should be made transparent, debated in the public domain and negotiated with women seeking antenatal care.

  1. Genital herpes simplex virus type 2 infection in humanized HIV-transgenic mice triggers HIV shedding and is associated with greater neurological disease.

    Science.gov (United States)

    Nixon, Briana; Fakioglu, Esra; Stefanidou, Martha; Wang, Yanhua; Dutta, Monica; Goldstein, Harris; Herold, Betsy C

    2014-02-15

    Epidemiological studies consistently demonstrate synergy between herpes simplex virus type 2 (HSV-2) and human immunodeficiency virus type 1 (HIV-1). Higher HIV-1 loads are observed in coinfected individuals, and conversely, HIV-1 is associated with more-severe herpetic disease. A small animal model of coinfection would facilitate identification of the biological mechanisms underlying this synergy and provide the opportunity to evaluate interventions. Mice transgenic for HIV-1 provirus and human cyclin T1 under the control of a CD4 promoter (JR-CSF/hu-cycT1) were intravaginally infected with HSV-2 and evaluated for disease progression, HIV shedding, and mucosal immune responses. HSV-2 infection resulted in higher vaginal HIV loads and genital tissue expression of HIV RNA, compared with HSV-uninfected JR-CSF/hu-cycT1 mice. There was an increase in genital tract inflammatory cells, cytokines, chemokines, and interferons in response to HSV-2, although the kinetics of the response were delayed in HIV-transgenic, compared with control mice. Moreover, the JR-CSF/hu-cycT1 mice exhibited earlier and more-severe neurological disease. The latter was associated with downregulation of secretory leukocyte protease inhibitor expression in neuronal tissue, a molecule with antiinflammatory, antiviral, and neuroprotective properties. JR-CSF/hu-cycT1 mice provide a valuable model to study HIV/HSV-2 coinfection and identify potential mechanisms by which HSV-2 facilitates HIV-1 transmission and HIV modulates HSV-2-mediated disease.

  2. Effective CD4+ T-cell restoration in gut-associated lymphoid tissue of HIV-infected patients is associated with enhanced Th17 cells and polyfunctional HIV-specific T-cell responses.

    Science.gov (United States)

    Macal, M; Sankaran, S; Chun, T-W; Reay, E; Flamm, J; Prindiville, T J; Dandekar, S

    2008-11-01

    Human immunodeficiency virus (HIV) infection leads to severe CD4+ T-cell depletion in gut-associated lymphoid tissue (GALT) that persists despite the initiation of highly active antiretroviral therapy (HAART). It is not known whether restoration of gut mucosal CD4+ T cells and their functions is feasible during therapy and how that relates to immune correlates and viral reservoirs. Intestinal biopsies and peripheral blood samples from HIV-infected patients who were either HAART naive or on long-term HAART were evaluated. Our data demonstrated that gut CD4+ T-cell restoration ranged from modest (50%), compared with uninfected controls. Despite persistent CD4+ T-cell proviral burden and residual immune activation in GALT during HAART, effective CD4+ T-cell restoration (>50%) was achieved, which was associated with enhanced Th17 CD4+ T-cell accumulation and polyfunctional anti-HIV cellular responses. Our findings suggest that a threshold of>50% CD4+ T-cell restoration may be sufficient for polyfunctional HIV-specific T cells with implications in the evaluation of vaccines and therapeutics.

  3. Comparison of a Clinical Prediction Rule and a LAM Antigen-Detection Assay for the Rapid Diagnosis of TBM in a High HIV Prevalence Setting

    Science.gov (United States)

    Patel, Vinod B.; Singh, Ravesh; Connolly, Cathy; Kasprowicz, Victoria; Zumla, Allimudin; Ndungu, Thumbi; Dheda, Keertan

    2010-01-01

    Background/Objective The diagnosis of tuberculous meningitis (TBM) in resource poor TB endemic environments is challenging. The accuracy of current tools for the rapid diagnosis of TBM is suboptimal. We sought to develop a clinical-prediction rule for the diagnosis of TBM in a high HIV prevalence setting, and to compare performance outcomes to conventional diagnostic modalities and a novel lipoarabinomannan (LAM) antigen detection test (Clearview-TB®) using cerebrospinal fluid (CSF). Methods Patients with suspected TBM were classified as definite-TBM (CSF culture or PCR positive), probable-TBM and non-TBM. Results Of the 150 patients, 84% were HIV-infected (median [IQR] CD4 count = 132 [54; 241] cells/µl). There were 39, 55 and 54 patients in the definite, probable and non-TBM groups, respectively. The LAM sensitivity and specificity (95%CI) was 31% (17;48) and 94% (85;99), respectively (cut-point ≥0.18). By contrast, smear-microscopy was 100% specific but detected none of the definite-TBM cases. LAM positivity was associated with HIV co-infection and low CD4 T cell count (CD4200 cells/µl; p = 0.03). The sensitivity and specificity in those with a CD4<100 cells/µl was 50% (27;73) and 95% (74;99), respectively. A clinical-prediction rule ≥6 derived from multivariate analysis had a sensitivity and specificity (95%CI) of 47% (31;64) and 98% (90;100), respectively. When LAM was combined with the clinical-prediction-rule, the sensitivity increased significantly (p<0.001) to 63% (47;68) and specificity remained high at 93% (82;98). Conclusions Despite its modest sensitivity the LAM ELISA is an accurate rapid rule-in test for TBM that has incremental value over smear-microscopy. The rule-in value of LAM can be further increased by combination with a clinical-prediction rule, thus enhancing the rapid diagnosis of TBM in HIV-infected persons with advanced immunosuppression. PMID:21203513

  4. HIV-1 subtype C superinfected individuals mount low autologous neutralizing antibody responses prior to intrasubtype superinfection

    Directory of Open Access Journals (Sweden)

    Basu Debby

    2012-09-01

    Full Text Available Abstract Background The potential role of antibodies in protection against intra-subtype HIV-1 superinfection remains to be understood. We compared the early neutralizing antibody (NAb responses in three individuals, who were superinfected within one year of primary infection, to ten matched non-superinfected controls from a Zambian cohort of subtype C transmission cases. Sequence analysis of single genome amplified full-length envs from a previous study showed limited diversification in the individuals who became superinfected with the same HIV-1 subtype within year one post-seroconversion. We hypothesized that this reflected a blunted NAb response, which may have made these individuals more susceptible to superinfection. Results Neutralization assays showed that autologous plasma NAb responses to the earliest, and in some cases transmitted/founder, virus were delayed and had low to undetectable titers in all three superinfected individuals prior to superinfection. In contrast, NAbs with a median IC50 titer of 1896 were detected as early as three months post-seroconversion in non-superinfected controls. Early plasma NAbs in all subjects showed limited but variable levels of heterologous neutralization breadth. Superinfected individuals also exhibited a trend toward lower levels of gp120- and V1V2-specific IgG binding antibodies but higher gp120-specific plasma IgA binding antibodies. Conclusions These data suggest that the lack of development of IgG antibodies, as reflected in autologous NAbs as well as gp120 and V1V2 binding antibodies to the primary infection virus, combined with potentially competing, non-protective IgA antibodies, may increase susceptibility to superinfection in the context of settings where a single HIV-1 subtype predominates.

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

    Science.gov (United States)

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

    2017-10-01

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

  6. A Novel Method for Determining the Inhibitory Potential of Anti-HIV Drugs

    Science.gov (United States)

    Shen, Lin; Rabi, S. Alireza; Siliciano, Robert F.

    2009-01-01

    In the absence of a cure, most HIV-1-infected individuals will require life-long treatment. It is therefore essential to optimize highly active antiretroviral therapy. Recent research has shown that the slope parameter or Hill coefficient, which describes the steepness of a dose-response curve, is a critical missing dimension in the evaluation of antiviral drug activity. Based on this finding, the instantaneous inhibitory potential (IIP) has been derived as a new measure of antiviral drug activity. IIP incorporates the slope parameter and thus is a more accurate pharmacodynamic measure of antiviral activity than current measures such as IC50 and inhibitory quotient. However, it remains important to determine how to use IIP to predict the in vivo efficacy of anti-HIV-1 drugs. This article discusses recent advances in in vitro measures of antiviral activity and the therapeutic implications of the dose-response curve slope and IIP. PMID:19837466

  7. Corporate social responsibility in public health: A case-study on HIV/AIDS epidemic by Johnson & Johnson company in Africa

    OpenAIRE

    Chattu, Vijay Kumar

    2015-01-01

    HIV/AIDS has claimed millions of lives in the global workforce and continues to remain a threat to many businesses. An estimated 36.5 million of working people are living with HIV; the global workforce has lost 28 million people from AIDS since the beginning of the epidemic. In the absence of access to treatment, this number could grow to 74 million by 2015. The epidemic continues to affect the working population through absenteeism, sickness and death. Corporate Social Responsibility (CSR) i...

  8. A novel simple QSAR model for the prediction of anti-HIV activity using multiple linear regression analysis.

    Science.gov (United States)

    Afantitis, Antreas; Melagraki, Georgia; Sarimveis, Haralambos; Koutentis, Panayiotis A; Markopoulos, John; Igglessi-Markopoulou, Olga

    2006-08-01

    A quantitative-structure activity relationship was obtained by applying Multiple Linear Regression Analysis to a series of 80 1-[2-hydroxyethoxy-methyl]-6-(phenylthio) thymine (HEPT) derivatives with significant anti-HIV activity. For the selection of the best among 37 different descriptors, the Elimination Selection Stepwise Regression Method (ES-SWR) was utilized. The resulting QSAR model (R (2) (CV) = 0.8160; S (PRESS) = 0.5680) proved to be very accurate both in training and predictive stages.

  9. Is phototherapy safe for HIV-infected individuals?

    Energy Technology Data Exchange (ETDEWEB)

    Adams, M.L.; Houpt, K.R.; Cruz, P.D. Jr. [Texas Univ., Dallas, TX (United States). Southwestern Medical Center

    1996-08-01

    Patients infected with human immunodeficiency virus (HIV) have a high prevalence of UV radiation-responsive skin diseases including psoriasis, pruitus, eosinophillic folliculitis and eczemas. On the other hand, UV has been shown to suppress T cell-mediated immune responses and to induce activation and replication of HIV. These developments have prompted clinicians and investigators to question whether phototherapy is safe for HIV-infected individuals. We have reviewed these issues and hereby provide a summary and critique of relevant laboratory and clinical evidence. (Author).

  10. Determinants of vaccine immunogenicity in HIV-infected pregnant women: analysis of B and T cell responses to pandemic H1N1 monovalent vaccine.

    Directory of Open Access Journals (Sweden)

    Adriana Weinberg

    Full Text Available Influenza infections have high frequency and morbidity in HIV-infected pregnant women, underscoring the importance of vaccine-conferred protection. To identify the factors that determine vaccine immunogenicity in this group, we characterized the relationship of B- and T-cell responses to pandemic H1N1 (pH1N1 vaccine with HIV-associated immunologic and virologic characteristics. pH1N1 and seasonal-H1N1 (sH1N1 antibodies were measured in 119 HIV-infected pregnant women after two double-strength pH1N1 vaccine doses. pH1N1-IgG and IgA B-cell FluoroSpot, pH1N1- and sH1N1-interferon γ (IFNγ and granzyme B (GrB T-cell FluoroSpot, and flow cytometric characterization of B- and T-cell subsets were performed in 57 subjects. pH1N1-antibodies increased after vaccination, but less than previously described in healthy adults. pH1N1-IgG memory B cells (Bmem increased, IFNγ-effector T-cells (Teff decreased, and IgA Bmem and GrB Teff did not change. pH1N1-antibodies and Teff were significantly correlated with each other and with sH1N1-HAI and Teff, respectively, before and after vaccination. pH1N1-antibody responses to the vaccine significantly increased with high proportions of CD4+, low CD8+ and low CD8+HLADR+CD38+ activated (Tact cells. pH1N1-IgG Bmem responses increased with high proportions of CD19+CD27+CD21- activated B cells (Bact, high CD8+CD39+ regulatory T cells (Treg, and low CD19+CD27-CD21- exhausted B cells (Bexhaust. IFNγ-Teff responses increased with low HIV plasma RNA, CD8+HLADR+CD38+ Tact, CD4+FoxP3+ Treg and CD19+IL10+ Breg. In conclusion, pre-existing antibody and Teff responses to sH1N1 were associated with increased responses to pH1N1 vaccination in HIV-infected pregnant women suggesting an important role for heterosubtypic immunologic memory. High CD4+% T cells were associated with increased, whereas high HIV replication, Tact and Bexhaust were associated with decreased vaccine immunogenicity. High Treg increased antibody responses but

  11. Neural Correlates of Risk Perception: HIV vs. Leukemia

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    Alexander eBarth

    2013-11-01

    Full Text Available Field studies on HIV risk perception suggest that people may rely on impressions they have about the safety of their partner. Previous studies show that individuals perceived as 'risky' regarding HIV elicit a differential brain response in both earlier (~200 - 350 ms and later (~350 - 700 ms time windows compared to those perceived as safe. This raises the question whether this ERP response is specific to contagious life-threatening diseases or a general mechanism triggered by life-threatening but non-contagious diseases. In the present study, we recorded dense sensor EEG while participants (N = 36 evaluated photographs of unacquainted individuals for either HIV or leukemia risk. The ERP results replicated previous findings revealing earlier and later differential brain responses towards individuals perceived as high risk for HIV. However, there were no significant ERP differences for high vs. low leukemia risk. Rather than reflecting a generic response to disease, the present findings suggest that intuitive judgments of HIV risk are at least in part specific to sexually transmitted diseases.

  12. Plasma levels of soluble CD14 independently predict mortality in HIV infection

    DEFF Research Database (Denmark)

    Sandler, Netanya G; Wand, Handan; Roque, Annelys

    2011-01-01

    Chronic human immunodeficiency virus (HIV) infection is associated with intestinal permeability and microbial translocation that contributes to systemic immune activation, which is an independent predictor of HIV disease progression. The association of microbial translocation with clinical outcom...

  13. An inappropriate tool: criminal law and HIV in Asia.

    Science.gov (United States)

    Csete, Joanne; Dube, Siddharth

    2010-09-01

    Asian countries have applied criminal sanctions widely in areas directly relevant to national HIV programmes and policies, including criminalization of HIV transmission, sex work, homosexuality and drug injection. This criminalization may impede universal access to HIV prevention and treatment services in Asia and undermine vulnerable people's ability to be part of the HIV response. To review the status of application of criminal law in key HIV-related areas in Asia and analyze its impact. Review of literature and application of human rights norms to analysis of criminal law measures. Criminal laws in the areas considered here and their enforcement, while intended to reduce HIV transmission, are inappropriate and counterproductive with respect to health and human rights. Governments should remove punitive laws that impede the HIV response and should ensure meaningful participation of people living with HIV, people who use illicit drugs, sex workers and men who have sex with men in combating stigma and discrimination and developing rights-centered approaches to HIV.

  14. Prediction Models for Dynamic Demand Response

    Energy Technology Data Exchange (ETDEWEB)

    Aman, Saima; Frincu, Marc; Chelmis, Charalampos; Noor, Muhammad; Simmhan, Yogesh; Prasanna, Viktor K.

    2015-11-02

    As Smart Grids move closer to dynamic curtailment programs, Demand Response (DR) events will become necessary not only on fixed time intervals and weekdays predetermined by static policies, but also during changing decision periods and weekends to react to real-time demand signals. Unique challenges arise in this context vis-a-vis demand prediction and curtailment estimation and the transformation of such tasks into an automated, efficient dynamic demand response (D2R) process. While existing work has concentrated on increasing the accuracy of prediction models for DR, there is a lack of studies for prediction models for D2R, which we address in this paper. Our first contribution is the formal definition of D2R, and the description of its challenges and requirements. Our second contribution is a feasibility analysis of very-short-term prediction of electricity consumption for D2R over a diverse, large-scale dataset that includes both small residential customers and large buildings. Our third, and major contribution is a set of insights into the predictability of electricity consumption in the context of D2R. Specifically, we focus on prediction models that can operate at a very small data granularity (here 15-min intervals), for both weekdays and weekends - all conditions that characterize scenarios for D2R. We find that short-term time series and simple averaging models used by Independent Service Operators and utilities achieve superior prediction accuracy. We also observe that workdays are more predictable than weekends and holiday. Also, smaller customers have large variation in consumption and are less predictable than larger buildings. Key implications of our findings are that better models are required for small customers and for non-workdays, both of which are critical for D2R. Also, prediction models require just few days’ worth of data indicating that small amounts of

  15. Hierarchy Low CD4+/CD8+ T-Cell Counts and IFN-γ Responses in HIV-1+ Individuals Correlate with Active TB and/or M.tb Co-Infection.

    Science.gov (United States)

    Shao, Lingyun; Zhang, Xinyun; Gao, Yan; Xu, Yunya; Zhang, Shu; Yu, Shenglei; Weng, Xinhua; Shen, Hongbo; Chen, Zheng W; Jiang, Weimin; Zhang, Wenhong

    2016-01-01

    Detailed studies of correlation between HIV-M.tb co-infection and hierarchy declines of CD8+/CD4+ T-cell counts and IFN-γ responses have not been done. We conducted case-control studies to address this issue. 164 HIV-1-infected individuals comprised of HIV-1+ATB, HIV-1+LTB and HIV-1+TB- groups were evaluated. Immune phenotyping and complete blood count (CBC) were employed to measure CD4+ and CD8+ T-cell counts; T.SPOT.TB and intracellular cytokine staining (ICS) were utilized to detect ESAT6, CFP10 or PPD-specific IFN-γ responses. There were significant differences in median CD4+ T-cell counts between HIV-1+ATB (164/μL), HIV-1+LTB (447/μL) and HIV-1+TB- (329/μL) groups. Hierarchy low CD4+ T-cell counts (500/μL) were correlated significantly with active TB but not M.tb co-infection. Interestingly, hierarchy low CD8+ T-cell counts were not only associated significantly with active TB but also with M.tb co-infection (PHierarchy low CD8+ T-cell counts and effector function in HIV-1-infected individuals are correlated with both M.tb co-infection and active TB. Hierarchy low CD4+ T-cell counts and Th1 effector function in HIV-1+ individuals are associated with increased frequencies of active TB, but not M.tb co-infection.

  16. Financing the response to HIV in low-income and middle-income countries.

    Science.gov (United States)

    Izazola-Licea, José Antonio; Wiegelmann, Jan; Arán, Christian; Guthrie, Teresa; De Lay, Paul; Avila-Figueroa, Carlos

    2009-12-01

    To describe levels of national HIV spending and examine programmatic allocations according to the type of epidemic and country income. Cross-sectional analysis of HIV expenditures from 50 low-income and middle-income countries. Sources of information included country reports of domestic spending by programmatic activity and HIV services. These HIV spending categories were cross tabulated by source of financing, stratified by type of HIV epidemic and income level of the country and reported in international dollars (I$). Fifty low-income and middle-income countries spent US $ 2.6 billion (I$ 5.8 billion) on HIV in 2006; 87% of the funding among the 17 low-income countries came from international donors. Average per capita spending was I$ 2.1 and positively correlated with Gross National Income. Per capita spending was I$ 1.5 in 9 countries with low-level HIV epidemics, I$ 1.6 in 27 countries with concentrated HIV epidemics and I$ 9.5 in 14 countries with generalized HIV epidemics. On average, spending on care and treatment represented 50% of AIDS spending across all countries. The treatment-to-prevention spending ratio was 1.5:1, 3:1, and 2:1 in countries with low-level, concentrated and generalized epidemics, respectively. Spending on prevention represented 21% of total AIDS spending. However, expenditures addressing most-at-risk populations represented less than 1% in countries with generalized epidemics and 7% in those with low-level or concentrated epidemics. The most striking finding is the mismatch between the types of HIV epidemics and the allocation of resources. The current global economic recession will force countries to rethink national strategies, especially in low-income countries with high aid dependency. Mapping HIV expenditures provides crucial guidance for reallocation of resources and supports evidence-based decisions. Now more than ever, countries need to know and act on their epidemics and give priority to the most effective programmatic

  17. Protecting HIV information in countries scaling up HIV services: a baseline study.

    Science.gov (United States)

    Beck, Eduard J; Mandalia, Sundhiya; Harling, Guy; Santas, Xenophon M; Mosure, Debra; Delay, Paul R

    2011-02-06

    Individual-level data are needed to optimize clinical care and monitor and evaluate HIV services. Confidentiality and security of such data must be safeguarded to avoid stigmatization and discrimination of people living with HIV. We set out to assess the extent that countries scaling up HIV services have developed and implemented guidelines to protect the confidentiality and security of HIV information. Questionnaires were sent to UNAIDS field staff in 98 middle- and lower-income countries, some reportedly with guidelines (G-countries) and others intending to develop them (NG-countries). Responses were scored, aggregated and weighted to produce standard scores for six categories: information governance, country policies, data collection, data storage, data transfer and data access. Responses were analyzed using regression analyses for associations with national HIV prevalence, gross national income per capita, OECD income, receiving US PEPFAR funding, and being a G- or NG-country. Differences between G- and NG-countries were investigated using non-parametric methods. Higher information governance scores were observed for G-countries compared with NG-countries; no differences were observed between country policies or data collection categories. However, for data storage, data transfer and data access, G-countries had lower scores compared with NG-countries. No significant associations were observed between country score and HIV prevalence, per capita gross national income, OECD economic category, and whether countries had received PEPFAR funding. Few countries, including G-countries, had developed comprehensive guidelines on protecting the confidentiality and security of HIV information. Countries must develop their own guidelines, using established frameworks to guide their efforts, and may require assistance in adapting, adopting and implementing them.

  18. Impact of viral hepatitis co-infection on response to antiretroviral therapy and HIV disease progression in the HIV-NAT cohort

    NARCIS (Netherlands)

    Law, W. Phillip; Duncombe, Chris J.; Mahanontharit, Apicha; Boyd, Mark A.; Ruxrungtham, Kiat; Lange, Joep M. A.; Phanuphak, Praphan; Cooper, David A.; Dore, Gregory J.

    2004-01-01

    OBJECTIVE: To examine the impact of viral hepatitis co-infection on HIV disease outcomes following commencement of combination antiretroviral therapy in a developing country setting. METHODS: HIV RNA suppression, CD4 cell count recovery, and HIV disease progression were examined within a cohort of

  19. HIV/AIDS status disclosure increases support, behavioural change and, HIV prevention in the long term: a case for an Urban Clinic, Kampala, Uganda.

    Science.gov (United States)

    Atuyambe, Lynn Muhimbuura; Ssegujja, Eric; Ssali, Sarah; Tumwine, Christopher; Nekesa, Nicolate; Nannungi, Annette; Ryan, Gery; Wagner, Glenn

    2014-06-21

    Disclosure of HIV status supports risk reduction and facilitates access to prevention and care services, but can be inhibited by the fear of negative repercussions. We explored the short and long-term outcomes of disclosure among clients attending an urban HIV clinic in Uganda. Qualitative semi-structured interviews were administered to a purposeful sample of 40 adult HIV clients that was stratified by gender. The information elicited included their lived experiences and outcomes of disclosure in the short and long term. A text data management software (ATLAS.ti) was used for data analysis. Codes were exported to MS Excel and pivot tables, and code counts made to generate statistical data. Of the 134 short-term responses elicited during the interview regarding disclosure events, most responses were supportive including encouragement, advice and support regarding HIV care and treatment. The results show on-disclosing to spouse, there was more trust, and use of condoms for HIV prevention. Only one third were negative responses, like emotional shock and feeling of distress. The negative reactions to the spouses included rejection, shock and distress in the short term. Even then, none of these events led to drastic change such as divorce. Other responses reflected HIV prevention and call for behavioural change and advice to change sexual behaviour, recipient seeking HIV testing or care. Women reported more responses of encouragement compared to men. Men reported more preventive behaviour compared to women. Of the 137 long-term outcomes elicited during disclosure, three quarters were positive followed by behavioral change and prevention, and then negative responses. Men reported increased care and support when they disclosed to fellow men compared to when women disclosed to women. There was better or not change in relationship when women disclosed to women than when women disclosed to men. There is overwhelming support to individuals that disclose their HIV status

  20. QSAR models for prediction study of HIV protease inhibitors using support vector machines, neural networks and multiple linear regression

    Directory of Open Access Journals (Sweden)

    Rachid Darnag

    2017-02-01

    Full Text Available Support vector machines (SVM represent one of the most promising Machine Learning (ML tools that can be applied to develop a predictive quantitative structure–activity relationship (QSAR models using molecular descriptors. Multiple linear regression (MLR and artificial neural networks (ANNs were also utilized to construct quantitative linear and non linear models to compare with the results obtained by SVM. The prediction results are in good agreement with the experimental value of HIV activity; also, the results reveal the superiority of the SVM over MLR and ANN model. The contribution of each descriptor to the structure–activity relationships was evaluated.

  1. Is an HIV vaccine possible?

    Directory of Open Access Journals (Sweden)

    Nancy A. Wilson

    Full Text Available The road to the discovery of a vaccine for HIV has been arduous and will continue to be difficult over the ensuing twenty years. Most vaccines are developed by inducing neutralizing antibodies against the target pathogen or by using attenuated strains of the particular pathogen to engender a variety of protective immune responses. Unfortunately, simple methods of generating anti-HIV antibodies have already failed in a phase III clinical trial. While attenuated SIV variants work well against homologous challenges in non-human primates, the potential for reversion to a more pathogenic virus and recombination with challenge viruses will preclude the use of attenuated HIV in the field. It has been exceedingly frustrating to vaccinate for HIV-specific neutralizing antibodies given the enormous diversity of the Envelope (Env glycoprotein and its well-developed glycan shield. However, there are several antibodies that will neutralize many different strains of HIV and inducing these types of antibodies in vaccinees remains the goal of a vigorous effort to develop a vaccine for HIV based on neutralizing antibodies. Given the difficulty in generating broadly reactive neutralizing antibodies, the HIV vaccine field has turned its attention to inducing T cell responses against the virus using a variety of vectors. Unfortunately, the results from Merck's phase IIb STEP trial proved to be disappointing. Vaccinees received Adenovirus type 5 (Ad5 expressing Gag, Pol, and Nef of HIV. This vaccine regimen failed to either prevent infection or reduce the level of HIV replication after challenge. These results mirrored those in non-human primate testing of Ad5 using rigorous SIV challenge models. This review will focus on recent developments in HIV vaccine development. We will deal largely with attempts to develop a T cell-based vaccine using the non-human primate SIV challenge model.

  2. Challenge and response: HIV in Asia and the Pacific.

    Science.gov (United States)

    Dwyer, J M; Mahathir, M; Nath, L M

    1996-11-04

    Inexorably, the epicentre of the global HIV pandemic is moving from Africa to Asia. Despite many years of much-publicised analysis of the African epidemic, most countries in Asia and many in the Pacific have not introduced the public health strategies known to minimise the spread of HIV. What must be done now, and how can the developed countries in the region, such as Australia, assist their neighbours?

  3. Bacterial vaginosis, human papilloma virus and herpes viridae do not predict vaginal HIV RNA shedding in women living with HIV in Denmark

    DEFF Research Database (Denmark)

    Wessman, Maria; Thorsteinsson, Kristina; Jensen, Jørgen S

    2017-01-01

    in the genital tract despite undetectable HIV RNA plasma viral load. We examined the prevalence and diagnostic predictors of BV and HIV-1 RNA vaginal shedding in women living with HIV (WLWH) in Denmark, taking into account the presence of human papillomavirus (HPV) and herpes viridae. Methods: WLWH between 18...

  4. Superior control of HIV-1 replication by CD8+ T cells targeting conserved epitopes: implications for HIV vaccine design.

    Directory of Open Access Journals (Sweden)

    Pratima Kunwar

    Full Text Available A successful HIV vaccine will likely induce both humoral and cell-mediated immunity, however, the enormous diversity of HIV has hampered the development of a vaccine that effectively elicits both arms of the adaptive immune response. To tackle the problem of viral diversity, T cell-based vaccine approaches have focused on two main strategies (i increasing the breadth of vaccine-induced responses or (ii increasing vaccine-induced responses targeting only conserved regions of the virus. The relative extent to which set-point viremia is impacted by epitope-conservation of CD8(+ T cell responses elicited during early HIV-infection is unknown but has important implications for vaccine design. To address this question, we comprehensively mapped HIV-1 CD8(+ T cell epitope-specificities in 23 ART-naïve individuals during early infection and computed their conservation score (CS by three different methods (prevalence, entropy and conseq on clade-B and group-M sequence alignments. The majority of CD8(+ T cell responses were directed against variable epitopes (p<0.01. Interestingly, increasing breadth of CD8(+ T cell responses specifically recognizing conserved epitopes was associated with lower set-point viremia (r = - 0.65, p = 0.009. Moreover, subjects possessing CD8(+ T cells recognizing at least one conserved epitope had 1.4 log10 lower set-point viremia compared to those recognizing only variable epitopes (p = 0.021. The association between viral control and the breadth of conserved CD8(+ T cell responses may be influenced by the method of CS definition and sequences used to determine conservation levels. Strikingly, targeting variable versus conserved epitopes was independent of HLA type (p = 0.215. The associations with viral control were independent of functional avidity of CD8(+ T cell responses elicited during early infection. Taken together, these data suggest that the next-generation of T-cell based HIV-1 vaccines should focus

  5. Serological Response to Treatment of Syphilis with Doxycycline Compared with Penicillin in HIV-infected Individuals

    DEFF Research Database (Denmark)

    Salado-Rasmussen, Kirsten; Hoffmann, Steen; Cowan, Susan

    2016-01-01

    Serological response to treatment of syphilis with orally administered doxycycline or intramuscularly administered penicillin was assessed in patients with concurrent HIV. All HIV-infected individuals diagnosed with syphilis attending 3 hospitals in Copenhagen, Denmark were included. Odds ratios...... (ORs) with 95% confidence intervals (CI) associated with serological outcome were modelled using propensity-score-adjusted logistic regression analysis. In total, 202 cases were treated with doxycycline or intramuscular penicillin. At 12 months, serological failure was observed in 12 cases (15......%) treated with doxycycline and in 8 cases (17%) treated with penicillin (OR 0.78 (95% CI 0.16-3.88), p = 0.76). The serological cure rate at 12 months was highest in patients with primary syphilis (100%), followed by patients with secondary (89%), early latent (71%) and late latent (67%) syphilis (p = 0...

  6. Copy number variation of Fc gamma receptor genes in HIV-infected and HIV-tuberculosis co-infected individuals in sub-Saharan Africa.

    Directory of Open Access Journals (Sweden)

    Lee R Machado

    Full Text Available AIDS, caused by the retrovirus HIV, remains the largest cause of morbidity in sub-Saharan Africa yet almost all genetic studies have focused on cohorts from Western countries. HIV shows high co-morbidity with tuberculosis (TB, as HIV stimulates the reactivation of latent tuberculosis (TB. Recent clinical trials suggest that an effective anti-HIV response correlates with non-neutralising antibodies. Given that Fcγ receptors are critical in mediating the non-neutralising effects of antibodies, analysis of the extensive variation at Fcγ receptor genes is important. Single nucleotide variation and copy number variation (CNV of Fcγ receptor genes affects the expression profile, activatory/inhibitory balance, and IgG affinity of the Fcγ receptor repertoire of each individual. In this study we investigated whether CNV of FCGR2C, FCGR3A and FCGR3B as well as the HNA1 allotype of FCGR3B is associated with HIV load, response to highly-active antiretroviral therapy (HAART and co-infection with TB. We confirmed an effect of TB-co-infection status on HIV load and response to HAART, but no conclusive effect of the genetic variants we tested. We observed a small effect, in Ethiopians, of FCGR3B copy number, where deletion was more frequent in HIV-TB co-infected patients than those infected with HIV alone.

  7. HIV-1 Subtype C Mosaic Gag Expressed by BCG and MVA Elicits Persistent Effector T Cell Responses in a Prime-Boost Regimen in Mice.

    Directory of Open Access Journals (Sweden)

    Tsungai Ivai Jongwe

    Full Text Available Over 90% of HIV/AIDS positive individuals in sub-Saharan Africa are infected with highly heterogeneous HIV-1 subtype C (HIV-1C viruses. One of the best ways to reduce the burden of this disease is the development of an affordable and effective prophylactic vaccine. Mosaic immunogens are computationally designed to overcome the hurdle of HIV diversity by maximizing the expression of potential T cell epitopes. Mycobacterium bovis BCG ΔpanCD auxotroph and modified vaccinia Ankara (MVA vaccines expressing HIV-1C mosaic Gag (GagM were tested in a prime-boost regimen to demonstrate immunogenicity in a mouse study. The BCG-GagM vaccine was stable and persisted 11.5 weeks post vaccination in BALB/c mice. Priming with BCG-GagM and boosting with MVA-GagM elicited higher Gag-specific IFN-γ ELISPOT responses than the BCG-GagM only and MVA-GagM only homologous vaccination regimens. The heterologous vaccination also generated a more balanced and persistent CD4+ and CD8+ T cell Gag-specific IFN-γ ELISPOT response with a predominant effector memory phenotype. A Th1 bias was induced by the vaccines as determined by the predominant secretion of IFN-γ, TNF-α, and IL-2. This study shows that a low dose of MVA (104 pfu can effectively boost a BCG prime expressing the same mosaic immunogen, generating strong, cellular immune responses against Gag in mice. Our data warrants further evaluation in non-human primates. A low dose vaccine would be an advantage in the resource limited countries of sub-Saharan Africa and India (where the predominating virus is HIV-1 subtype C.

  8. Complement and the control of HIV infection: an evolving story.

    Science.gov (United States)

    Frank, Michael M; Hester, Christopher; Jiang, Haixiang

    2014-05-01

    Thirty years ago, investigators isolated and later determined the structure of HIV-1 and its envelope proteins. Using techniques that were effective with other viruses, they prepared vaccines designed to generate antibody or T-cell responses, but they were ineffective in clinical trials. In this article, we consider the role of complement in host defense against enveloped viruses, the role it might play in the antibody response and why complement has not controlled HIV-1 infection. Complement consists of a large group of cell-bound and plasma proteins that are an integral part of the innate immune system. They provide a first line of defense against microbes and also play a role in the immune response. Here we review the studies of complement-mediated HIV destruction and the role of complement in the HIV antibody response. HIV-1 has evolved a complex defense to prevent complement-mediated killing reviewed here. As part of these studies, we have discovered that HIV-1 envelope, on administration into animals, is rapidly broken down into small peptides that may prove to be very inefficient at provident the type of antigenic stimulation that leads to an effective immune response. Improving complement binding and stabilizing envelope may improve the vaccine response.

  9. [The HIV infection - the limits of prevention concepts. Consideration with respect to responsibilities incumbent on the infected individual, politics and society at large].

    Science.gov (United States)

    Dennin, R H; Doese, D; Theobald, W; Lafrenz, M

    2007-04-01

    Despite the introduction of campaigns to prevent the continued spread of HIV/AIDS in Germany, the number of annual firsttime HIV-diagnoses is continuing steadily. The concepts behind the current campaigns are largely based on models of New Public Health, of which social learning strategies are an essential element. The established personal and individual rights should be unimpeachable but the right not to know the status of HIV infection should be questioned for those people who spread their HIV infection intentionally and wilfully. Confronted with more than 10,000 people in Germany unconscious of their HIV infection, easy access to HIV testing and access of opportune therapy should be offered with the goal of reducing the number of new infections. Expanded strategies on the responsibility to one's personal health and that of the partner, understandable and adapted to special groups of the society, should be established and maintained at a high level of awareness. All measures must be performed voluntarily.

  10. Schistosomiasis and HIV in rural Zimbabwe: efficacy of treatment of schistosomiasis in individuals with HIV coinfection

    DEFF Research Database (Denmark)

    Kallestrup, Per; Zinyama, Rutendo; Gomo, Exnevia

    2006-01-01

    There is evidence from experimental models that the praziquantel-induced clearance of schistosomiasis is dependent on the host's immune response. Consequently, human immunodeficiency virus (HIV)-related immunodeficiency may impair the effect of praziquantel treatment.......There is evidence from experimental models that the praziquantel-induced clearance of schistosomiasis is dependent on the host's immune response. Consequently, human immunodeficiency virus (HIV)-related immunodeficiency may impair the effect of praziquantel treatment....

  11. The expanding role of civil society in the global HIV/AIDS response: what has the President's Emergency Program For AIDS Relief's role been?

    Science.gov (United States)

    Coutinho, Alex; Roxo, Uchechi; Epino, Henry; Muganzi, Alex; Dorward, Emily; Pick, Billy

    2012-08-15

    Civil society has been part of the HIV/AIDS response from the very beginning of the epidemic, often becoming engaged before national governments. Traditional roles of civil society--advocacy, activism, serving as government watchdog, and acting as community caretaker--have been critical to the response. In addition, civil society organizations (CSOs) play an integral part in providing world-class HIV prevention and treatment services and helping to ensure continuity of care. The President's Emergency Program for AIDS Relief (PEPFAR) has significantly increased the global scale-up of combination antiretroviral therapy reaching for more than 5 million people in developing countries, as well as implementation of effective evidence-based combination prevention approaches. PEPFAR databases in 5 countries and annual reports from a centrally managed initiative were mined and analyzed to determine the numbers and types of CSOs funded by PEPFAR over a 5-year period (2006-2011). Data are also presented from Uganda showing the overall resource growth in CSO working for HIV. Case studies document the evolution of 3 indigenous CSOs that increased the capacity to implement activities with PEPFAR funding. A legacy of PEPFAR has been the growth of civil society to address social and health issues as well as recognition by governments that partnerships with beneficiaries and civil society result in better outcomes. Scale-up of the global response could not have happened without the involvement of civil society and people living with HIV. This game changing partnership to jointly tackle the problems that countries face may well be the greatest benefit emerging from the HIV epidemic.

  12. Chimeric rhinoviruses displaying MPER epitopes elicit anti-HIV neutralizing responses.

    Directory of Open Access Journals (Sweden)

    Guohua Yi

    Full Text Available The development of an effective AIDS vaccine has been a formidable task, but remains a critical necessity. The well conserved membrane-proximal external region (MPER of the HIV-1 gp41 glycoprotein is one of the crucial targets for AIDS vaccine development, as it has the necessary attribute of being able to elicit antibodies capable of neutralizing diverse isolates of HIV.Guided by X-ray crystallography, molecular modeling, combinatorial chemistry, and powerful selection techniques, we designed and produced six combinatorial libraries of chimeric human rhinoviruses (HRV displaying the MPER epitopes corresponding to mAbs 2F5, 4E10, and/or Z13e1, connected to an immunogenic surface loop of HRV via linkers of varying lengths and sequences. Not all libraries led to viable chimeric viruses with the desired sequences, but the combinatorial approach allowed us to examine large numbers of MPER-displaying chimeras. Among the chimeras were five that elicited antibodies capable of significantly neutralizing HIV-1 pseudoviruses from at least three subtypes, in one case leading to neutralization of 10 pseudoviruses from all six subtypes tested.Optimization of these chimeras or closely related chimeras could conceivably lead to useful components of an effective AIDS vaccine. While the MPER of HIV may not be immunodominant in natural infection by HIV-1, its presence in a vaccine cocktail could provide critical breadth of protection.

  13. Predicting the response of olfactory sensory neurons to odor mixtures from single odor response

    Science.gov (United States)

    Marasco, Addolorata; de Paris, Alessandro; Migliore, Michele

    2016-04-01

    The response of olfactory receptor neurons to odor mixtures is not well understood. Here, using experimental constraints, we investigate the mathematical structure of the odor response space and its consequences. The analysis suggests that the odor response space is 3-dimensional, and predicts that the dose-response curve of an odor receptor can be obtained, in most cases, from three primary components with specific properties. This opens the way to an objective procedure to obtain specific olfactory receptor responses by manipulating mixtures in a mathematically predictable manner. This result is general and applies, independently of the number of odor components, to any olfactory sensory neuron type with a response curve that can be represented as a sigmoidal function of the odor concentration.

  14. Patient Characteristics Associated with HCV Treatment Adherence, Treatment Completion, and Sustained Virologic Response in HIV Coinfected Patients

    Directory of Open Access Journals (Sweden)

    Glenn Wagner

    2011-01-01

    Full Text Available Background. Hepatitis C (HCV treatment efficacy among HIV patients is limited by poor treatment adherence and tolerance, but few studies have examined the psychosocial determinants of treatment adherence and outcomes. Methods. Chart abstracted and survey data were collected on 72 HIV patients who had received pegylated interferon and ribavirin to assess correlates of treatment adherence, completion, and sustained virologic response (SVR. Results. Nearly half (46% the sample had active psychiatric problems and 13% had illicit drug use at treatment onset; 28% reported <100% treatment adherence, 38% did not complete treatment (mostly due to virologic nonresponse, and intent to treat SVR rate was 49%. Having a psychiatric diagnosis was associated with nonadherence, while better HCV adherence was associated with both treatment completion and SVR. Conclusions. Good mental health may be an indicator of HCV treatment adherence readiness, which is in turn associated with treatment completion and response, but further research is needed with new HCV treatments emerging.

  15. HIV-1 proteins dysregulate motivational processes and dopamine circuitry.

    Science.gov (United States)

    Bertrand, Sarah J; Mactutus, Charles F; Harrod, Steven B; Moran, Landhing M; Booze, Rosemarie M

    2018-05-18

    Motivational alterations, such as apathy, in HIV-1+ individuals are associated with decreased performance on tasks involving frontal-subcortical circuitry. We used the HIV-1 transgenic (Tg) rat to assess effect of long-term HIV-1 protein exposure on motivated behavior using sucrose (1-30%, w/v) and cocaine (0.01-1.0 mg/kg/infusion) maintained responding with fixed-ratio (FR) and progressive-ratio (PR) schedules of reinforcement. For sucrose-reinforced responding, HIV-1 Tg rats displayed no change in EC 50 relative to controls, suggesting no change in sucrose reinforcement but had a downward shifted concentration-response curves, suggesting a decrease in response vigor. Cocaine-maintained responding was attenuated in HIV-1 Tg rats (FR1 0.33 mg/kg/infusion and PR 1.0 mg/kg/infusion). Dose-response tests (PR) revealed that HIV-1 Tg animals responded significantly less than F344 control rats and failed to earn significantly more infusions of cocaine as the unit dose increased. When choosing between cocaine and sucrose, control rats initially chose sucrose but with time shifted to a cocaine preference. In contrast, HIV-1 disrupted choice behaviors. DAT function was altered in the striatum of HIV-1 Tg rats; however, prior cocaine self-administration produced a unique effect on dopamine homeostasis in the HIV-1 Tg striatum. These findings of altered goal directed behaviors may determine neurobiological mechanisms of apathy in HIV-1+ patients.

  16. Ambient air pollution associated with suppressed serologic responses to Pneumocystis jirovecii in a prospective cohort of HIV-infected patients with Pneumocystis pneumonia.

    Directory of Open Access Journals (Sweden)

    Robert J Blount

    Full Text Available Ambient air pollution (AAP may be associated with increased risk for Pneumocystis pneumonia (PCP. The mechanisms underlying this association remain uncertain.To determine if real-life exposures to AAP are associated with suppressed IgM antibody responses to P. jirovecii in HIV-infected (HIV+ patients with active PCP, and to determine if AAP, mediated by suppressed serologic responses to Pneumocystis, is associated with adverse clinical outcomes.We conducted a prospective cohort study in HIV+ patients residing in San Francisco and admitted to San Francisco General Hospital with microscopically confirmed PCP. Our AAP predictors were ambient air concentrations of particulate matter of < 10 µm in diameter (PM10 and < 2.5 µm in diameter (PM2.5, nitrogen dioxide (NO2, ozone (O3, and sulfur dioxide (SO2 measured immediately prior to hospital admission and 2 weeks prior to admission. Our primary outcomes were the IgM serologic responses to four recombinant P. jirovecii major surface glycoprotein (Msg constructs: MsgC1, MsgC3, MsgC8, and MsgC9.Elevated PM10 and NO2 exposures immediately prior to and two weeks prior to hospital admission were associated with decreased IgM antibody responses to P. jirovecii Msg. For exposures immediately prior to admission, every 10 µg/m(3 increase in PM10 was associated with a 25 to 35% decrease in IgM responses to Msg (statistically significant for all the Msg constructs, and every 10 ppb increase in NO2 was associated with a 19-45% decrease in IgM responses to Msg (statistically significant for MsgC8 and MsgC9. Similar findings were seen with exposures two weeks prior to admission, but for fewer of the Msg constructs.Real life exposures to PM10 and NO2 were associated with suppressed IgM responses to P. jirovecii Msg in HIV+ patients admitted with PCP, suggesting a mechanism of immunotoxicity by which AAP increases host susceptibility to pulmonary infection.

  17. Thirty Years with HIV Infection-Nonprogression Is Still Puzzling

    DEFF Research Database (Denmark)

    Gaardbo, Julie C; Hartling, Hans J; Gerstoft, Jan

    2012-01-01

    , host differences in the immunological response have been proposed. Moreover, the immunological response can be divided into an immune homeostasis resistant to HIV and an immune response leading to viral control. Thus, non-progression in LTNP and controllers may be due to different immunological...... mechanisms. Understanding the lack of disease progression and the different interactions between HIV and the immune system could ideally teach us how to develop a functional cure for HIV infection. Here we review immunological features of controllers and LTNP, highlighting differences and clinical...

  18. Soil transmitted helminth infections are not associated with compromised antibody responses to previously administered measles and tetanus vaccines among HIV-1 infected, ART naïve Kenyan adults

    Directory of Open Access Journals (Sweden)

    Helen L. Storey

    2017-02-01

    Full Text Available In many regions of sub-Saharan Africa, both HIV and helminth infections are prevalent. HIV-1 (human immunodeficiency virus type 1 and helminth infections can both compromise immune responses in humans. To determine whether the presence of helminth infection or the treatment of helminth infection alters unstimulated vaccine responses among HIV-1 infected individuals, we conducted two nested serologic studies. Blood samples were collected for HIV disease monitoring and vaccine-specific serologic assays, while stool was evaluated by direct microscopy methods. We compared antibody responses to measles and tetanus vaccines in helminth-infected (Ascaris, Trichuris, hookworm and/or Schistosoma mansoni and uninfected adults 18 years and older (n = 100. We also compared measles and tetanus antibody responses in Ascaris only-infected adults receiving 400 mg albendazole daily for 3 days (n = 16 vs. placebo (n = 19 in a separate study. In both cohorts, over 70% of participants had measles and tetanus responses above the protective threshold. Prevalence of measles responses were similar between helminth-infected and uninfected individuals (82%, 95% CI: 71–93% vs 72%, 95% CI: 59–85%, as well as log10 tetanus antibody levels (−0.133 IU/mL vs −0.190 IU/mL, p > 0.05, and did not differ by helminth species. In the Ascaris-infected cohort, changes in measles responses and tetanus responses did not differ between those who received anthelminthic vs. placebo (p > 0.05 for both. In these studies, neither helminth infection, nor deworming, appeared to affect previously administered vaccine responsiveness in HIV-1 infected, ART naïve, adults in Kenya.

  19. Two-year prospective study of major depressive disorder in HIV-infected men.

    Science.gov (United States)

    Atkinson, J Hampton; Heaton, Robert K; Patterson, Thomas L; Wolfson, Tanya; Deutsch, Reena; Brown, Stephen J; Summers, J; Sciolla, A; Gutierrez, R; Ellis, Ronald J; Abramson, Ian; Hesselink, John R; McCutchan, J Allen; Grant, Igor

    2008-06-01

    The risks and factors contributing to major depressive episodes in HIV infection remain unclear. This 2-year prospective study compared cumulative rates and predictors of a major depressive episode in HIV-infected (HIV+) men (N=297) and uninfected (HIV-) risk-group controls (N=90). By design participants at entry were without current major depression, substance dependence or major anxiety disorder. Standardized neuromedical, neuropsychological, neuroimaging, life events, and psychiatric assessments (Structured Clinical Interview for DSM III-R) were conducted semi-annually for those with AIDS, and annually for all others. Lifetime prevalence of major depression or other psychiatric disorder did not differ at baseline between HIV+ men and controls. On a two-year follow-up those with symptomatic HIV disease were significantly more likely to experience a major depressive episode than were asymptomatic HIV+ individuals and HIV-controls (pdepression. After baseline disease stage and medical variables associated with HIV infection were controlled, a lifetime history of major depression, or of lifetime psychiatric comorbidity (two or more psychiatric disorders), predicted subsequent major depressive episode (pdepressive episode. Research cohort of men examined before era of widespread use of advanced anti-HIV therapies. Symptomatic HIV disease, but not HIV infection itself, increases intermediate-term risk of major depression. Prior psychiatric history most strongly predicted future vulnerability.

  20. Diagnostic accuracy and acceptability of rapid HIV oral testing among adults attending an urban public health facility in Kampala, Uganda.

    Directory of Open Access Journals (Sweden)

    Joanita Nangendo

    Full Text Available The prevalence of HIV in Uganda is 7.3%, and yet nearly 40% of people living with HIV are unaware of their status. The current HIV testing policy which is strictly blood-based poses several challenges including: a need for high level laboratory skills, stringent waste disposal needs, and painful sample collection. It is envisaged that introduction of a rapid, painless HIV oral fluid test as a potential alternative is likely to increase the number of people testing. The aim of this study was to determine the diagnostic accuracy and acceptability of rapid HIV oral testing among adults attending Kisenyi Health Centre IV in Kampala.We conducted a cross-sectional study among 440 adults recruited consecutively at Kisenyi Health Centre IV from January to March 2016. The diagnostic accuracy of the HIV oral test was assessed by comparing to the national HIV serial testing algorithm. We also assessed for acceptability among patients and health care workers (HCWs by triangulating responses from a structured questionnaire, three focus group discussions and seven key informant interviews. Acceptability was defined as willingness to take the test at the time of the study and intention for future use of the test if it was availed. The prevalence of HIV infection among study participants was 14.8%. The HIV oral fluid test was highly accurate with sensitivity of 100% (95% CI; 94.5-100.0, specificity of 100% (95% CI; 99.0-100.0, positive predictive value (PPV of 100% (95% CI; 94.5-100.0 and negative predictive value (NPV of 100% (95% CI; 99.0-100.0. Acceptability of HIV oral testing was also high at 87.0% (95% CI; 83.6-89.9. Participants preferred HIV oral testing because it was: pain free (91%, n = 399 and did not require blood draw (82%, n = 360.The HIV oral fluid test has high diagnostic accuracy and acceptability. HIV oral testing is a suitable addition to the national HIV testing strategies with the potential of increasing access to HIV testing services in

  1. Dopamine reward prediction error responses reflect marginal utility.

    Science.gov (United States)

    Stauffer, William R; Lak, Armin; Schultz, Wolfram

    2014-11-03

    Optimal choices require an accurate neuronal representation of economic value. In economics, utility functions are mathematical representations of subjective value that can be constructed from choices under risk. Utility usually exhibits a nonlinear relationship to physical reward value that corresponds to risk attitudes and reflects the increasing or decreasing marginal utility obtained with each additional unit of reward. Accordingly, neuronal reward responses coding utility should robustly reflect this nonlinearity. In two monkeys, we measured utility as a function of physical reward value from meaningful choices under risk (that adhered to first- and second-order stochastic dominance). The resulting nonlinear utility functions predicted the certainty equivalents for new gambles, indicating that the functions' shapes were meaningful. The monkeys were risk seeking (convex utility function) for low reward and risk avoiding (concave utility function) with higher amounts. Critically, the dopamine prediction error responses at the time of reward itself reflected the nonlinear utility functions measured at the time of choices. In particular, the reward response magnitude depended on the first derivative of the utility function and thus reflected the marginal utility. Furthermore, dopamine responses recorded outside of the task reflected the marginal utility of unpredicted reward. Accordingly, these responses were sufficient to train reinforcement learning models to predict the behaviorally defined expected utility of gambles. These data suggest a neuronal manifestation of marginal utility in dopamine neurons and indicate a common neuronal basis for fundamental explanatory constructs in animal learning theory (prediction error) and economic decision theory (marginal utility). Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

  2. Interferon α subtypes in HIV infection.

    Science.gov (United States)

    Sutter, Kathrin; Dickow, Julia; Dittmer, Ulf

    2018-02-13

    Type I interferons (IFN), which are immediately induced after most virus infections, are central for direct antiviral immunity and link innate and adaptive immune responses. However, several viruses have evolved strategies to evade the IFN response by preventing IFN induction or blocking IFN signaling pathways. Thus, therapeutic application of exogenous type I IFN or agonists inducing type I IFN responses are a considerable option for future immunotherapies against chronic viral infections. An important part of the type I IFN family are 12 IFNα subtypes, which all bind the same receptor, but significantly differ in their biological activities. Up to date only one IFNα subtype (IFNα2) is being used in clinical treatment against chronic virus infections, however its therapeutic success rate is rather limited, especially during Human Immunodeficiency Virus (HIV) infection. Recent studies addressed the important question if other IFNα subtypes would be more potent against retroviral infections in in vitro and in vivo experiments. Indeed, very potent IFNα subtypes were defined and their antiviral and immunomodulatory properties were characterized. In this review we summarize the recent findings on the role of individual IFNα subtypes during HIV and Simian Immunodeficiency Virus infection. This includes their induction during HIV/SIV infection, their antiretroviral activity and the regulation of immune response against HIV by different IFNα subtypes. The findings might facilitate novel strategies for HIV cure or functional cure studies. Copyright © 2018 Elsevier Ltd. All rights reserved.

  3. Predicting fluid responsiveness with transthoracic echocardiography is not yet evidence based

    DEFF Research Database (Denmark)

    Wetterslev, M; Haase, N; Johansen, R R

    2013-01-01

    an integrated tool in the intensive care unit, this systematic review examined studies evaluating the predictive value of TTE for fluid responsiveness. In October 2012, we searched Pubmed, EMBASE and Web of Science for studies evaluating the predictive value of TTE-derived variables for fluid responsiveness...... responsiveness. Of the 4294 evaluated citations, only one study fully met our inclusion criteria. In this study, the predictive value of variations in inferior vena cava diameter (> 16%) for fluid responsiveness was moderate with sensitivity of 71% [95% confidence interval (CI) 44-90], specificity of 100% (95......% CI 73-100) and an area under the receiver operating curve of 0.90 (95% CI 0.73-0.98). Only one study of TTE-based methods fulfilled the criteria for valid assessment of fluid responsiveness. Before recommending the use of TTE in predicting fluid responsiveness, proper evaluation including...

  4. Lack of definitive severe mitochondrial signs and symptoms among deceased HIV-uninfected and HIV-indeterminate children

    NARCIS (Netherlands)

    Dominguez, K; Bertolli, J; Fowler, M; Peters, [No Value; Ortiz, [No Value; Melville, S; Rakusan, T; Frederick, T; Hsu, H; D'Almada, P; Maldonado, Y; Wilfert, C; Ammann, AJ; Rubinstein, A

    2000-01-01

    Background: In response to recent reports of mitochondrial dysfunction in HIV-uninfected infants exposed to antiretroviral (ARV) prophylaxis., the Perinatal Safety Review Working Group reviewed deaths in five large HIV-exposed perinatal cohorts in the United States to determine if similar cases of

  5. A neuropsychological investigation of multitasking in HIV infection: implications for everyday functioning.

    Science.gov (United States)

    Scott, J Cobb; Woods, Steven Paul; Vigil, Ofilio; Heaton, Robert K; Schweinsburg, Brian C; Ellis, Ronald J; Grant, Igor; Marcotte, Thomas D

    2011-07-01

    A subset of individuals with HIV-associated neurocognitive impairment experience related deficits in "real world" functioning (i.e., independently performing instrumental activities of daily living [IADL]). While performance-based tests of everyday functioning are reasonably sensitive to HIV-associated IADL declines, questions remain regarding the extent to which these tests' highly structured nature fully captures the inherent complexities of daily life. The aim of this study was to assess the predictive and ecological validity of a novel multitasking measure in HIV infection. Participants included 60 individuals with HIV infection (HIV+) and 25 demographically comparable seronegative adults (HIV-). Participants were administered a comprehensive neuropsychological battery, questionnaires assessing mood and everyday functioning, and a novel standardized test of multitasking, which involved balancing the demands of four interconnected performance-based functional tasks (i.e., financial management, cooking, medication management, and telephone communication). HIV+ individuals demonstrated significantly worse overall performance, fewer simultaneous task attempts, and increased errors on the multitasking test as compared to the HIV- group. Within the HIV+ sample, multitasking impairments were modestly associated with deficits on standard neuropsychological measures of executive functions, episodic memory, attention/working memory, and information processing speed, providing preliminary evidence for convergent validity. More importantly, multivariate prediction models revealed that multitasking deficits were uniquely predictive of IADL dependence beyond the effects of depression and global neurocognitive impairment, with excellent sensitivity (86%), but modest specificity (57%). Taken together, these data indicate that multitasking ability may play an important role in successful everyday functioning in HIV+ individuals. PsycINFO Database Record (c) 2011 APA, all rights

  6. Aripiprazole Improves Depressive Symptoms and Immunological Response to Antiretroviral Therapy in an HIV-Infected Subject with Resistant Depression

    Directory of Open Access Journals (Sweden)

    Chiara Cecchelli

    2010-01-01

    Full Text Available Aripiprazole is the first medication approved by the FDA as an add-on treatment for MDD. The impact of aripiprazole on the response to HIV is unknown. The patient we report on was diagnosed HIV-positive in 1997 and has been treated with antiretroviral therapy since then. In 2008, we diagnosed resistant major depression, hypochondria, and panic disorder. On that occasion, blood tests showed a significantly reduced CD4 count and a positive viral load. We treated this patient with aripiprazole and citalopram. Mood, somatic symptoms, and occupational functioning progressively improved. The last blood examination showed an increase in the CD4 count and a negative viral load. On the basis of the present case study and the review of the literature concerning the effects of psychotropic agents on viral replication, we suggest that the use of aripiprazole in HIV-infected subjects warrants further research.

  7. Maternal HIV Serostatus, Mother–Daughter Sexual Risk Communication and Adolescent HIV Risk Beliefs and Intentions

    Science.gov (United States)

    Hutchinson, M. Katherine; Duan, Lei; Jemmott, Loretta S.

    2012-01-01

    Daughters of HIV-positive women are often exposed to the same factors that placed their mothers at risk. This cross-sectional study (N = 176 dyads) examined HIV status, parent-teen sexual risk communication (PTSRC), and daughters’ abstinence and condom use beliefs and intentions. Maternal HIV status was not associated with PTSRC. Path analyses show that maternal depression was associated with PTSRC behavioral and normative beliefs; relationship satisfaction was associated with PTSRC normative and control beliefs. Control beliefs were solely predictive of maternal PTSRC intention. PTSRC was associated with adolescent behavioral and normative beliefs. Abstinence beliefs were associated with abstinence intentions; condom beliefs were associated with condom use intentions. Relationship satisfaction was associated with adolescent control beliefs about both abstinence and condom use. There is a need for interventions that help HIV-positive mothers recognize their daughter’s HIV risk and provide them with relationship building and parent process skills to help reduce these risks. PMID:22677973

  8. Maternal HIV serostatus, mother-daughter sexual risk communication and adolescent HIV risk beliefs and intentions.

    Science.gov (United States)

    Cederbaum, Julie A; Hutchinson, M Katherine; Duan, Lei; Jemmott, Loretta S

    2013-09-01

    Daughters of HIV-positive women are often exposed to the same factors that placed their mothers at risk. This cross-sectional study (N = 176 dyads) examined HIV status, parent-teen sexual risk communication (PTSRC), and daughters' abstinence and condom use beliefs and intentions. Maternal HIV status was not associated with PTSRC. Path analyses show that maternal depression was associated with PTSRC behavioral and normative beliefs; relationship satisfaction was associated with PTSRC normative and control beliefs. Control beliefs were solely predictive of maternal PTSRC intention. PTSRC was associated with adolescent behavioral and normative beliefs. Abstinence beliefs were associated with abstinence intentions; condom beliefs were associated with condom use intentions. Relationship satisfaction was associated with adolescent control beliefs about both abstinence and condom use. There is a need for interventions that help HIV-positive mothers recognize their daughter's HIV risk and provide them with relationship building and parent process skills to help reduce these risks.

  9. HIV/AIDS Prevention Trials Capacity Building Grants - Phase II ...

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

    Canada's international response to the HIV/AIDS epidemic is largely built around the work of the Canadian HIV Vaccine Initiative (CHVI). CHVI proposes to increase the capacity of Canada and low- and middle-income countries to respond to the HIV/AIDS pandemic by developing new HIV vaccines and other preventive ...

  10. Enhanced glucagon-like peptide-1 (GLP-1) response to oral glucose in glucose-intolerant HIV-infected patients on antiretroviral therapy

    DEFF Research Database (Denmark)

    Andersen, O; Haugaard, S B; Holst, Jens Juul

    2005-01-01

    concentrations of GLP-1 and GIP were determined frequently during a 3-h, 75-g glucose tolerance test. Insulin secretion rates (ISRs) were calculated by deconvolution of C-peptide concentrations. RESULTS: The incremental area under the curve (incrAUC) for GLP-1 was increased by 250% in IGT patients compared...... without adjustment (r=0.38, Pglucose incrAUC (r=0.49, Pglucose-intolerant, HIV-infected male patients may display enhanced GLP-1 responses to oral glucose compared with normal glucose-tolerant HIV-infected male patients......OBJECTIVES: We investigated whether the incretin hormones glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), which are major regulators of glucose tolerance through the stimulation of insulin secretion, contribute to impaired glucose tolerance (IGT) among HIV...

  11. HIV-derived vectors for gene therapy targeting dendritic cells.

    Science.gov (United States)

    Rossetti, Maura; Cavarelli, Mariangela; Gregori, Silvia; Scarlatti, Gabriella

    2013-01-01

    Human immunodeficiency virus type 1 (HIV-1)-derived lentiviral vectors (LV) have the potential to mediate stable therapeutic gene transfer. However, similarly to other viral vectors, their benefit is compromised by the induction of an immune response toward transgene-expressing cells that closely mimics antiviral immunity. LV share with the parental HIV the ability to activate dendritic cells (DC), while lack the peculiar ability of subverting DC functions, which is responsible for HIV immune escape. Understanding the interaction between LV and DC, with plasmacytoid and myeloid DC playing fundamental and distinct roles, has paved the way to novel approaches aimed at regulating transgene-specific immune responses. Thanks to the ability to target either DC subsets LV might be a powerful tool to induce immunity (i.e., gene therapy of cancer), cell death (i.e., in HIV/AIDS infection), or tolerance (i.e., gene therapy strategies for monogenic diseases). In this chapter, similarities and differences between the LV-mediated and HIV-mediated induction of immune responses, with specific focus on their interactions with DC, are discussed.

  12. Characterizing Class-Specific Exposure-Viral Load Suppression Response of HIV Antiretrovirals Using A Model-Based Meta-Analysis.

    Science.gov (United States)

    Xu, Y; Li, Y F; Zhang, D; Dockendorf, M; Tetteh, E; Rizk, M L; Grobler, J A; Lai, M-T; Gobburu, J; Ankrom, W

    2016-08-01

    We applied model-based meta-analysis of viral suppression as a function of drug exposure and in vitro potency for short-term monotherapy in human immunodeficiency virus type 1 (HIV-1)-infected treatment-naïve patients to set pharmacokinetic targets for development of nonnucleoside reverse transcriptase inhibitors (NNRTIs) and integrase strand transfer inhibitors (InSTIs). We developed class-specific models relating viral load kinetics from monotherapy studies to potency normalized steady-state trough plasma concentrations. These models were integrated with a literature assessment of doses which demonstrated to have long-term efficacy in combination therapy, in order to set steady-state trough concentration targets of 6.17- and 2.15-fold above potency for NNRTIs and InSTIs, respectively. Both the models developed and the pharmacokinetic targets derived can be used to guide compound selection during preclinical development and to predict the dose-response of new antiretrovirals to inform early clinical trial design. © 2016 The Authors. Clinical and Translational Science published by Wiley Periodicals, Inc. on behalf of American Society for Clinical Pharmacology and Therapeutics.

  13. Ex vivo analysis identifies effective HIV-1 latency–reversing drug combinations

    Science.gov (United States)

    Laird, Gregory M.; Bullen, C. Korin; Rosenbloom, Daniel I.S.; Martin, Alyssa R.; Hill, Alison L.; Durand, Christine M.; Siliciano, Janet D.; Siliciano, Robert F.

    2015-01-01

    Reversal of HIV-1 latency by small molecules is a potential cure strategy. This approach will likely require effective drug combinations to achieve high levels of latency reversal. Using resting CD4+ T cells (rCD4s) from infected individuals, we developed an experimental and theoretical framework to identify effective latency-reversing agent (LRA) combinations. Utilizing ex vivo assays for intracellular HIV-1 mRNA and virion production, we compared 2-drug combinations of leading candidate LRAs and identified multiple combinations that effectively reverse latency. We showed that protein kinase C agonists in combination with bromodomain inhibitor JQ1 or histone deacetylase inhibitors robustly induce HIV-1 transcription and virus production when directly compared with maximum reactivation by T cell activation. Using the Bliss independence model to quantitate combined drug effects, we demonstrated that these combinations synergize to induce HIV-1 transcription. This robust latency reversal occurred without release of proinflammatory cytokines by rCD4s. To extend the clinical utility of our findings, we applied a mathematical model that estimates in vivo changes in plasma HIV-1 RNA from ex vivo measurements of virus production. Our study reconciles diverse findings from previous studies, establishes a quantitative experimental approach to evaluate combinatorial LRA efficacy, and presents a model to predict in vivo responses to LRAs. PMID:25822022

  14. Five Myths about the HIV Epidemic in Asia

    OpenAIRE

    Godwin, Peter; O'Farrell, Nigel; Fylkesnes, Knut; Misra, Sujaya

    2006-01-01

    It is widely recognised that the huge population sizes of many Asian countries mean that although national HIV prevalence levels are still very low, very large absolute numbers of people are being infected each year with HIV [1]. Urgent responses are required; the effective responses by countries such as Thailand and Cambodia have shown how much can be done. As implementers who have worked with HIV/AIDS programmes in several countries in the region, we recognise the public health and welf...

  15. Factors for Predicting Outcomes among Non-HIV Patients with Pulmonary Tuberculosis

    Science.gov (United States)

    Tsukahara, Toshinori; Horita, Nobuyuki; Tashiro, Ken; Nagai, Kenjiro; Shinkai, Masaharu; Yamamoto, Masaki; Sato, Takashi; Hara, Yu; Nagakura, Hideyuki; Shibata, Yuji; Watanabe, Hiroki; Nakashima, Kentaro; Ushio, Ryota; Nagashima, Akimichi; Ikeda, Misako; Narita, Atsuya; Sasaki, Katsuhito; Kobayashi, Nobuaki; Kudo, Makoto; Kaneko, Takeshi

    2017-01-01

    Objective Onodera's Prognostic Nutritional Index (PNI), determined as “10× albumin (g/dL) + 0.005× lymphocyte count (/μL),” was originally designed to determine the risk of complications following gastrointestinal surgery. This single-center, retrospective observational study was designed to investigate whether or not the PNI can predict the treatment outcome. Methods We consecutively reviewed HIV-negative pulmonary tuberculosis adults in an isolation ward. Most patients were being treated with standard three- or four-drug regimens. Patients were discharged after consecutive negative smears/cultures were confirmed. The risk of all-cause death was assessed using a multivariable Cox proportional hazard model and a log-rank trend test. Results During the observation period, we observed 371 consecutive patients with a median age of 72 (interquartile range [IQR]: 54-82) years. In our cohort, 295 (79.5%) patients were discharged alive, and 76 (20.5%) died in-hospital. Patients who died in-hospital had a lower PNI [median 21.2 (IQR: 18.5-25.9)] than those who were discharged alive [median 35.1 (IQR: 28.0-43.3); p<0.001]. The area under the receiver operating characteristic curve was 0.87. After dividing the patients based on the baseline PNI quartile, those patients with a lower PNI showed a poorer survival than those with a higher PNI (log-rank trend p<0.001). After adjusting for other baseline variables, the baseline PNI was still associated with in-hospital death with a hazard ratio of 0.86 (95% confidence interval: 0.82-0.91, p<0.001). Conclusion Our results showed that a low PNI was clearly related to a poor survival prognosis in smear-positive HIV-negative pulmonary tuberculosis inpatients. PMID:29021438

  16. What does sustainability mean in the HIV and AIDS response?

    Science.gov (United States)

    Oberth, Gemma; Whiteside, Alan

    2016-01-01

    Immense progress has been made in the fight against HIV and AIDS. Achieving and exceeding the AIDS targets for the Millennium Development Goals (MDGs) was accomplished, in large part, due to an unprecedented financial investment from the international community. Following an $800 million dip in donor disbursements in 2010, the discourse has since shifted to the need for greater sustainability of funding. But what does sustainability mean? Current efforts focus heavily on fiscal imperatives such as increasing domestic funding. This is important - needs are increasing at a faster rate than donor funding, especially with increased treatment coverage. The problem is that measures of financial sustainability tell very little about the actual sustainability of specific programmes, disease trajectories or enabling environments. Recognising that current definitions of sustainability lack clarity and depth, we offer a new six-tenet conceptualisation of what sustainability means in the HIV and AIDS response: (1) financial, (2) epidemiological, (3) political, (4) structural, (5) programmatic, and (6) human rights. Based on these, we examine examples of donor transitions for their approach to sustainability, including PEPFAR in South Africa, the Global Fund in Eastern Europe, and the Bill and Melinda Gates Foundation in India (Avahan). We conclude that sustainability must be understood within a broader framework beyond funding stability. We also recommend that certain interventions, such as programming for key populations, may have to continue to receive external support even if affected countries can afford to pay.

  17. Barriers to communication between HIV care providers (HCPs) and women living with HIV about child bearing

    DEFF Research Database (Denmark)

    Ddumba-Nyanzi, Ismael; Kaawa-Mafigiri, David; Johannessen, Helle

    2016-01-01

    Objectives: In the context of HIV clinical care, open discussion regarding sexual health and reproductive plans has become increasingly relevant. The aim of this paper is to explore barriers to communication between providers and women living with HIV regarding childbearing. Methods: In-depth int......Objectives: In the context of HIV clinical care, open discussion regarding sexual health and reproductive plans has become increasingly relevant. The aim of this paper is to explore barriers to communication between providers and women living with HIV regarding childbearing. Methods: In....... Results: Four themes emerged describing barriers to communication, from the HIV-positive women’s point of view: (i) provider indifference or opposition to childbearing post HIV diagnosis, (ii) anticipation of negative response from provider, (iii) provider’s emphasis on ‘scientific’ facts, (iv...

  18. Sieve analysis in HIV-1 vaccine efficacy trials.

    Science.gov (United States)

    Edlefsen, Paul T; Gilbert, Peter B; Rolland, Morgane

    2013-09-01

    The genetic characterization of HIV-1 breakthrough infections in vaccine and placebo recipients offers new ways to assess vaccine efficacy trials. Statistical and sequence analysis methods provide opportunities to mine the mechanisms behind the effect of an HIV vaccine. The release of results from two HIV-1 vaccine efficacy trials, Step/HVTN-502 (HIV Vaccine Trials Network-502) and RV144, led to numerous studies in the last 5 years, including efforts to sequence HIV-1 breakthrough infections and compare viral characteristics between the vaccine and placebo groups. Novel genetic and statistical analysis methods uncovered features that distinguished founder viruses isolated from vaccinees from those isolated from placebo recipients, and identified HIV-1 genetic targets of vaccine-induced immune responses. Studies of HIV-1 breakthrough infections in vaccine efficacy trials can provide an independent confirmation to correlates of risk studies, as they take advantage of vaccine/placebo comparisons, whereas correlates of risk analyses are limited to vaccine recipients. Through the identification of viral determinants impacted by vaccine-mediated host immune responses, sieve analyses can shed light on potential mechanisms of vaccine protection.

  19. In vitro stimulation of peripheral blood mononuclear cells (PBMC) from HIV- and HIV+ chancroid patients by Haemophilus ducreyi antigens.

    Science.gov (United States)

    Van Laer, L; Vingerhoets, J; Vanham, G; Kestens, L; Bwayo, J; Otido, J; Piot, P; Roggen, E

    1995-11-01

    The cellular immune responses to fractionated Haemophilus ducreyi antigens, coated on latex beads, were assessed in patients with chancroid and in controls, using an in vitro lymphocyte proliferation assay. Several fractions of H. ducreyi antigen revealed stimulating activity. However, only the molecular size ranges 91-78 kD, 59-29 kD, and 25-21 kD induced proliferation that may be specifically related to H. ducreyi infection. Lymphocytes from four HIV- patients, successfully treated for chancroid, were not stimulated by H. ducreyi antigen. In general, lymphocytes from HIV+ chancroid patients were less responsive to H. ducreyi antigen compared with those from HIV- chancroid patients. However, two HIV-infected patients showed exceptionally strong responses to high molecular weight fractions. To our knowledge this is the first report demonstrating that H. ducreyi contains specific T cell-stimulating antigens. Based on this work, further identification and purification of the T cell antigens is feasible.

  20. Treating depression in HIV-positive patients affects adherence

    African Journals Online (AJOL)

    2012-09-02

    Sep 2, 2012 ... reported that the number of people newly infected with HIV and the number .... and immunity. Subjects were ... of change in adherence as a response ..... retroviral drugs: Theorising contextual relationships. ... Drug-resistant HIV-1: The virus strikes back. ... persons with human immunodeficiency virus (HIV).

  1. Relationship between HIV stigma and self-isolation among people living with HIV in Tennessee.

    Directory of Open Access Journals (Sweden)

    Carolyn M Audet

    Full Text Available HIV stigma is a contributing factor to poor patient outcomes. Although HIV stigma has been documented, its impact on patient well-being in the southern US is not well understood.Thirty-two adults participated in cognitive interviews after completing the Berger HIV or the Van Rie stigma scale. Participant responses were probed to ensure the scales accurately measured stigma and to assess the impact stigma had on behavior.Three main themes emerged regarding HIV stigma: (1 negative attitudes, fear of contagion, and misperceptions about transmission; (2 acts of discrimination by families, friends, health care providers, and within the workplace; and (3 participants' use of self-isolation as a coping mechanism. Overwhelming reluctance to disclose a person's HIV status made identifying enacted stigma with a quantitative scale difficult.Fear of discrimination resulted in participants isolating themselves from friends or experiences to avoid disclosure. Participant unwillingness to disclose their HIV status to friends and family could lead to an underestimation of enacted HIV stigma in quantitative scales.

  2. IgM response to a human Pneumocystis carinii surface antigen in HIV-infected patients with pulmonary symptoms

    DEFF Research Database (Denmark)

    Lundgren, Bettina; Kovacs, J A; Mathiesen, Lars Reinhardt

    1993-01-01

    We have developed an ELISA to detect IgM antibodies to a major human Pneumocystis carinii surface antigen (gp95), and investigated the IgM response in 128 HIV-infected patients who underwent bronchoscopy for evaluation of pulmonary symptoms. Only 5 (4%) patients had IgM antibodies to P. carinii g...

  3. Women Living with HIV in Rural Areas. Implementing a Response using the HIV and AIDS Risk Assessment and Reduction Model

    Directory of Open Access Journals (Sweden)

    Sarah Bandali

    2014-01-01

    Full Text Available The global fight against HIV is progressing; however, women living in rural areas particularly in sub-Saharan Africa (SSA continue to face the devastating consequences of HIV and AIDS. Lack of knowledge and geographical barriers to HIV services are compounded by gender norms often limiting the negotiation of safe sexual practices among women living in rural areas. This paper discusses findings from a qualitative study conducted in rural areas of Mozambique examining factors that influenced women to engage in HIV risk-reduction practices. The findings from this study led to the emergence of an HIV and AIDS risk assessment and reduction (HARAR model, which is described in detail. The model helps in understanding gender-related factors influencing men and women to engage in risk-reduction practices, which can be used as a framework in other settings to design more nuanced and contextual policies and programs.

  4. No More Broken Promises: Challenges and Opportunities for Key Populations in Demanding More Transparency, Accountability, and Participation in the Global Response Against the HIV and AIDS Epidemic.

    Science.gov (United States)

    Chang Pico, Tomás A; Kohler, Jillian Clare; Hoffmann, Julia; Mungala, Lucy

    2017-12-01

    The global fight against HIV/AIDS continues to pose challenges: infection rates are on the rise in many settings, stigma and discrimination remain rampant, and the global response is under increasing financial pressure. There is a high risk of losing what has been achieved so far in the fight against HIV and AIDS, but also the momentum to meet the so-called Fast Track targets for 2030. In light of these trends, it is fundamental to focus on the human rights of key populations (KPs)-especially to health, non-discrimination, access to information, and to equal and meaningful participation in political and public affairs-by placing them at the center of the global HIV response. Such rights, and the demand for more transparency, accountability, and participation (TAP), have been recognized as both a necessary social justice imperative, and as a way to build more responsive, inclusive, and sustainable health systems. This article will argue that embracing TAP as key guiding principles of the global HIV response (especially in low- and middle-income countries) could have the potential to create the conditions for KPs to have their human rights fulfilled, and to expand their participation in the decision-making processes that guide the efforts against the epidemic. It will then propose a number of avenues for further engagement between different communities of practice in terms of research, agendas, and policy and practices that could be beneficial in maximizing the impact of the global efforts to end HIV/AIDS.

  5. Predictors of HIV/AIDS confirmation and differences by guardian status in HIV+ adolescents in Jamaica.

    Science.gov (United States)

    Pilgrim, N; Kershaw, T; Pierre, R B; Moore, J; Palmer, P; Davis, D; Christie, C D C

    2008-06-01

    Approximately 25% of the cumulative AIDS cases in Jamaica involve adolescents and young adults. However the lives of adolescents living with HIV within Jamaica and the Caribbean have been understudied. (1) To describe the sociodemographic characteristics of HIV+ Jamaican adolescents who have ever been a part of the Kingston Paediatric/Perinatal HIV Programme (KPAIDS) from September 1, 2002 to August 31, 2006 (2). To identify predictors of HIV/AIDS confirmation as well as factors associated or uniquely present in these adolescents by their guardian status. Seventy-two HIV+ adolescents, ages 10-19 years, were included. Factors studied included demographics as well as time to and time between HIV and AIDS confirmation. Data were analyzed by bivariate and multivariate statistics. The mean age of the adolescents was 12.6 +/- 2.8 years with slightly more males (52.8%) in the programme. There were equal proportions of adolescents living with HIV as with AIDS (43.1%). There were equal proportions who were lost to follow-up or deceased (8.3%). Twenty-two of them lived with parents, 25 with guardians and 18 in residential institutions. The primary mode of transmission was perinatal infection (68.1%), followed by sexual (20.8%), blood transfusion (2.9%) and unknown (8.3%). The mean time from HIV exposure to HIV confirmation and AIDS confirmation in mother-to-child transmission (MTCT) cases were 8.0 +/- 2.9 years and 9.6 +/- 3.3 years, respectively. In the multivariate analysis model, age and gender were significant in predicting time from HIV exposure to HIV confirmation. The majority of HIV-positive adolescents reside with parents and guardians and this might indicate support in spite of stigma and discrimination. However; the mean time to HIV confirmation in MTCT cases is quite long and must be reduced.

  6. HIV / AIDS in China: migrant population, drug injection responsible for increased transmission.

    Science.gov (United States)

    Thomas, J

    1998-01-01

    By 2000, China will have 1.2 million people infected with HIV and 33,000 people with AIDS. While HIV infection has been reported from almost all provinces and occupational groups in the country, HIV prevalence is highest among IV drug users in Yunnan province. The major source of infection elsewhere in China is through the receipt of tainted blood products and heterosexual intercourse. A National AIDS Committee was formed in October 1986 to advise the government on AIDS policy, and since 1990 to coordinate all AIDS prevention activities. The National Strategies Plan for AIDS/STD Prevention in China during 1996-2000 was prepared in 1995. China's in-country migrant labor population may become the most vulnerable to HIV infection. There are currently about 120 million migrant workers in China, of whom about half are registered, nonpermanent residents working in the fastest developing regions. The open nature of China's economy relative to recent past decades has made it difficult to monitor and control internal migration. Floating populations are the most difficult to reach with preventive health education and they tend to be deprived of access of health care. 61.4% of the migrant population is male and 40% are aged 20-24 years. China's traditional trade routes may be a factor in HIV infection. HIV/AIDS epidemiology, the synergy of STDs and AIDS in China, the international partnership in HIV/AIDS prevention in China, the role of international nongovernmental organizations in China, Hong Kong's contribution to AIDS prevention in China, awareness of the problems associated with HIV infection in China, and the challenges for AIDS-related work in China are discussed.

  7. Responses to the global HIV and AIDS pandemic: a study of the role of faith-based organisations in Lesotho.

    Science.gov (United States)

    Olowu, Dejo

    2015-01-01

    This article attempts to establish the key contribution by people of faith to the global HIV pandemic response, using Lesotho as a case study. Particular focus is paid to the work of selected religious organisations in Lesotho in this context, assessing their capacities to coordinate an effective HIV and AIDS action at the grassroots levels through education, health care, development, and social service activities. Empirical evaluations and findings regarding the level and quality of faith-based engagement in this field establish the basic premise of this article, namely, that faith-based organisations are contributing energy, expertise, and experience in order to achieve the commitment of the global commitment to advance universal access to HIV prevention, treatment, and support. Although the article is particularly focused on the Lesotho context, its tremendous implications for simulated studies and approaches across Sub-Saharan Africa are accentuated.

  8. Evaluation of simple rapid HIV assays and development of national rapid HIV test algorithms in Dar es Salaam, Tanzania.

    Science.gov (United States)

    Lyamuya, Eligius F; Aboud, Said; Urassa, Willy K; Sufi, Jaffer; Mbwana, Judica; Ndugulile, Faustin; Massambu, Charles

    2009-02-18

    Suitable algorithms based on a combination of two or more simple rapid HIV assays have been shown to have a diagnostic accuracy comparable to double enzyme-linked immunosorbent assay (ELISA) or double ELISA with Western Blot strategies. The aims of this study were to evaluate the performance of five simple rapid HIV assays using whole blood samples from HIV-infected patients, pregnant women, voluntary counseling and testing attendees and blood donors, and to formulate an alternative confirmatory strategy based on rapid HIV testing algorithms suitable for use in Tanzania. Five rapid HIV assays: Determine HIV-1/2 (Inverness Medical), SD Bioline HIV 1/2 3.0 (Standard Diagnostics Inc.), First Response HIV Card 1-2.0 (PMC Medical India Pvt Ltd), HIV1/2 Stat-Pak Dipstick (Chembio Diagnostic System, Inc) and Uni-Gold HIV-1/2 (Trinity Biotech) were evaluated between June and September 2006 using 1433 whole blood samples from hospital patients, pregnant women, voluntary counseling and testing attendees and blood donors. All samples that were reactive on all or any of the five rapid assays and 10% of non-reactive samples were tested on a confirmatory Inno-Lia HIV I/II immunoblot assay (Immunogenetics). Three hundred and ninety samples were confirmed HIV-1 antibody positive, while 1043 were HIV negative. The sensitivity at initial testing of Determine, SD Bioline and Uni-Gold was 100% (95% CI; 99.1-100) while First Response and Stat-Pak had sensitivity of 99.5% (95% CI; 98.2-99.9) and 97.7% (95% CI; 95.7-98.9), respectively, which increased to 100% (95% CI; 99.1-100) on repeat testing. The initial specificity of the Uni-Gold assay was 100% (95% CI; 99.6-100) while specificities were 99.6% (95% CI; 99-99.9), 99.4% (95% CI; 98.8-99.7), 99.6% (95% CI; 99-99.9) and 99.8% (95% CI; 99.3-99.9) for Determine, SD Bioline, First Response and Stat-Pak assays, respectively. There was no any sample which was concordantly false positive in Uni-Gold, Determine and SD Bioline assays. An

  9. 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.)

  10. 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.)

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

    Science.gov (United States)

    Li, Jonathan Z.; Heisey, Andrea; Ahmed, Hayat; Wang, Hongying; Zheng, Lu; Carrington, Mary; Wrin, Terri; Schooley, Robert T.; Lederman, Michael M.; Kuritzkes, Daniel R.

    2014-01-01

    Objectives To evaluate the impact of therapeutic HIV vaccination on the HIV reservoir, and assess the relationship of the viral reservoir with HIV-specific immune status and viral rebound kinetics. Design Retrospective analysis of ACTG A5197, a randomized, placebo-controlled trial of a therapeutic rAd5 HIV-1 gag vaccine. Methods Participants received vaccine/placebo at weeks 0, 4, and 26 prior to a 16-week analytic treatment interruption (ATI) at week 38. Cell-associated HIV-1 RNA and DNA (CA-RNA and CA-DNA) and HIV-1 residual viremia (RV) were quantified at weeks 0, 8, and 38. HIV-specific CD4+/CD8+ activity were assessed by an intracellular cytokine staining assay. Results At study entry, CA-RNA and CA-DNA levels were correlated inversely with the numbers of HIV-specific CD4+ interferon-γ-producing cells (CA-RNA: r = −0.23, P=0.03 and CA-DNA: r = −0.28, P<0.01, N=93). Therapeutic HIV vaccination induced HIV-specific CD4+ activity, but did not significantly affect levels of CA-RNA or CA-DNA. Vaccine recipients with undetectable RV at week 8 had higher frequencies of HIV-specific CD4+ and CD8+ interferon-γ-producing cells (undetectable versus detectable RV: 277 versus 161 CD4+ cells/106 lymphocytes, P=0.03 and 1326 versus 669 CD8+ cells/106 lymphocytes, P=0.04). Pre-ATI CA-RNA and CA-DNA were associated with post-ATI plasma HIV set point (CA-RNA: r = 0.51, P<0.01 and CA-DNA: r = 0.47, P<0.01). Conclusions Vaccine-induced T-cell responses were associated with a modest transient effect on RV, but more potent immune responses and/or combination treatment with latency-reversing agents are needed to reduce the HIV reservoir. HIV reservoir measures may act as biomarkers of post-ATI viral rebound kinetics. PMID:25254301

  12. Biomarkers of Progression after HIV Acute/Early Infection: Nothing Compares to CD4+ T-cell Count?

    Directory of Open Access Journals (Sweden)

    Gabriela Turk

    2018-01-01

    Full Text Available Progression of HIV infection is variable among individuals, and definition disease progression biomarkers is still needed. Here, we aimed to categorize the predictive potential of several variables using feature selection methods and decision trees. A total of seventy-five treatment-naïve subjects were enrolled during acute/early HIV infection. CD4+ T-cell counts (CD4TC and viral load (VL levels were determined at enrollment and for one year. Immune activation, HIV-specific immune response, Human Leukocyte Antigen (HLA and C-C chemokine receptor type 5 (CCR5 genotypes, and plasma levels of 39 cytokines were determined. Data were analyzed by machine learning and non-parametric methods. Variable hierarchization was performed by Weka correlation-based feature selection and J48 decision tree. Plasma interleukin (IL-10, interferon gamma-induced protein (IP-10, soluble IL-2 receptor alpha (sIL-2Rα and tumor necrosis factor alpha (TNF-α levels correlated directly with baseline VL, whereas IL-2, TNF-α, fibroblast growth factor (FGF-2 and macrophage inflammatory protein (MIP-1β correlated directly with CD4+ T-cell activation (p < 0.05. However, none of these cytokines had good predictive values to distinguish “progressors” from “non-progressors”. Similarly, immune activation, HIV-specific immune responses and HLA/CCR5 genotypes had low discrimination power. Baseline CD4TC was the most potent discerning variable with a cut-off of 438 cells/μL (accuracy = 0.93, κ-Cohen = 0.85. Limited discerning power of the other factors might be related to frequency, variability and/or sampling time. Future studies based on decision trees to identify biomarkers of post-treatment control are warrantied.

  13. HIV p24 as scaffold for presenting conformational HIV Env antigens.

    Directory of Open Access Journals (Sweden)

    Maria Tagliamonte

    Full Text Available Heterologous protein scaffolds engrafted with structurally defined HIV Env epitopes recognized by broadly neutralizing monoclonal antibodies (MAbs represent a promising strategy to elicit broad neutralizing antibodies. In such regards, a protein scaffold based on the HIV p24 CA protein is a highly attractive approach, providing also Gag epitopes for eliciting HIV non-neutralizing protective antibodies and specific CD4(+ and CD8(+ T cell responses. In the present study, computational techniques were employed to verify the presence of acceptor sites for conformational HIV Env epitopes and, as proof of concept, the analysis of HIV p24 CA-based scaffolds using a complete V3 loop in a MAb-bound conformation is presented. The V3-p24 epitope-scaffold proteins show the formation of capsomers made of hexamers similarly to the p24 wild type protein. Moreover, the conformational V3 loop presented on p24 scaffold is recognized by a panel of anti-V3 MAbs. The results suggest that HIV p24 CA protein has suitable acceptor sites for engrafting foreign epitopes, without disrupting the formation of capsomer hexamer structures, and that the V3 epitope does retain its antibody-bound conformation. This strongly support the feasibility of developing a scaffolding strategy based on p24 CA proteins displaying conformational minimal structural, antigenic HIV Env epitopes.

  14. Family physicians and HIV infection.

    Science.gov (United States)

    Hall, N; Crochette, N; Blanchi, S; Lavoix, A; Billaud, E; Baron, C; Abgueguen, P; Perré, P; Rabier, V

    2015-01-01

    We aimed to describe the current and desired involvement of family physicians (FPs) in the treatment of HIV patients (screening practices, potential training and patient follow-up) to reduce the duration and frequency of their hospital treatment. We conducted a descriptive cross-sectional survey between 2011 and 2012 with the support of COREVIH (Regional Coordinating Committee on HIV). We sent a self-assessment questionnaire to all FPs of the Pays de la Loire region to enquire about their HIV screening practices and expectations for the management of HIV patients. A total of 871 FPs completed the questionnaire (response rate: 30.4%). A total of 54.2% said to provide care to HIV patients; the mean number of HIV patients per FP was estimated at 1.4. With regard to HIV screening, 12.2% systematically suggest an HIV serology to their patients and 72.7% always suggest it to pregnant women. About 45.4% of responding FPs said to be willing to manage HIV patients (clinical and biological monitoring, compliance checks and prescription renewal). FPs mainly reported the lack of training and the low number of HIV patients as a barrier to their further involvement in the management of HIV patients. The responding FPs provide care to very few HIV patients. They are, however, willing to be more involved in the routine care of these patients. Medical training provided by COREVIH would help improve HIV screening. The management of HIV patients could thus be handed over to willing FPs. Copyright © 2015. Published by Elsevier SAS.

  15. 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

  16. Sexual behavior, risk perception, and HIV transmission can respond to HIV antiviral drugs and vaccines through multiple pathways

    Science.gov (United States)

    Tully, Stephen; Cojocaru, Monica; Bauch, Chris T.

    2015-01-01

    There has been growing use of highly active antiretroviral treatment (HAART) for HIV and significant progress in developing prophylactic HIV vaccines. The simplest theories of counterproductive behavioral responses to such interventions tend to focus on single feedback mechanisms: for instance, HAART optimism makes infection less scary and thus promotes risky sexual behavior. Here, we develop an agent based, age-structured model of HIV transmission, risk perception, and partner selection in a core group to explore behavioral responses to interventions. We find that interventions can activate not one, but several feedback mechanisms that could potentially influence decision-making and HIV prevalence. In the model, HAART increases the attractiveness of unprotected sex, but it also increases perceived risk of infection and, on longer timescales, causes demographic impacts that partially counteract HAART optimism. Both HAART and vaccination usually lead to lower rates of unprotected sex on the whole, but intervention effectiveness depends strongly on whether individuals over- or under-estimate intervention coverage. Age-specific effects cause sexual behavior and HIV prevalence to change in opposite ways in old and young age groups. For complex infections like HIV—where interventions influence transmission, demography, sexual behavior and risk perception—we conclude that evaluations of behavioral responses should consider multiple feedback mechanisms. PMID:26507957

  17. Predictive value of prostate-specific antigen for prostate cancer

    DEFF Research Database (Denmark)

    Shepherd, Leah; Borges, Alvaro Humberto; Ravn, Lene

    2014-01-01

    INTRODUCTION: Although prostate cancer (PCa) incidence is lower in HIV+ men than in HIV- men, the usefulness of prostate-specific antigen (PSA) screening in this population is not well defined and may have higher false negative rates than in HIV- men. We aimed to describe the kinetics and predict......INTRODUCTION: Although prostate cancer (PCa) incidence is lower in HIV+ men than in HIV- men, the usefulness of prostate-specific antigen (PSA) screening in this population is not well defined and may have higher false negative rates than in HIV- men. We aimed to describe the kinetics...... and predictive value of PSA in HIV+ men. METHODS: Men with PCa (n=21) and up to two matched controls (n=40) with prospectively stored plasma samples before PCa (or matched date in controls) were selected. Cases and controls were matched on date of first and last sample, age, region of residence and CD4 count...... at first sample date. Total PSA (tPSA), free PSA (fPSA), testosterone and sex hormone binding globulin (SHBG) were measured. Conditional logistic regression models investigated associations between markers and PCa. Sensitivity and specificity of using tPSA >4 µg/L to predict PCa was calculated. Mixed...

  18. Antiretroviral treatment adherence as a mediating factor between psychosocial variables and HIV viral load.

    Science.gov (United States)

    Attonito, Jennifer; Dévieux, Jessy G; Lerner, Brenda D G; Hospital, Michelle M; Rosenberg, Rhonda

    2014-01-01

    Psychosocial factors may directly impact HIV health measures such as viral load (VL) whether or not patients are taking antiretroviral treatment (ART) consistently. Structural equation modeling plus Baron and Kenny's (1986) four-step approach were used to test a mediated model predicting VL among 246 HIV-infected adults who were on ART. Exogenous variables were social support, barriers to adherence, and stress. Moderators were alcohol use, marijuana use, and neurocognitive impairment. A small positive association between marijuana use and ART adherence approached significance. Only barriers to adherence predicted a decrease in adherence rates and an increase in VL. No other factors were significantly associated with either VL or adherence, and no interaction effects between exogenous variables and moderators were identified. The association between barriers to adherence and VL was partially mediated by ART adherence. Findings provide modest support for a direct link between psychosocial variables and a virologic response to ART. Copyright © 2014 Association of Nurses in AIDS Care. Published by Elsevier Inc. All rights reserved.

  19. Impact of hepatitis B virus co-infection on response to highly active antiretroviral treatment and outcome in HIV-infected individuals

    DEFF Research Database (Denmark)

    Omland, L H; Weis, N; Skinhøj, P

    2008-01-01

    BACKGROUND: The impact of chronic hepatitis B virus (HBV) infection on viral suppression, immune recovery and mortality in HIV-1 infected patients on highly active antiretroviral treatment (HAART) is a matter of debate. The impact of HBeAg status is unknown. METHODS: This prospective cohort study.......6%). Study endpoints were viral load, CD4 cell count and mortality. RESULTS: HBV co-infection had no impact on response to HAART regarding viral suppression or immune recovery. HBV co-infection was associated with several outcomes: overall mortality [mortality rate ratio (MRR) 1.5; 95% confidence interval...... (CI) 1.1-2.1], liver-related mortality (MRR 4.0; 95% CI 1.6-9.9) and AIDS-related deaths (MRR 1.7; 95% CI 1.0-3.0). The presence of HBeAg did not influence patients' response to HAART. CONCLUSIONS: In HIV patients, chronic HBV infection has no impact on response to HAART concerning viral load...

  20. Islamic perspectives on HIV/AIDS and antiretroviral treatment: the case of Nigeria.

    Science.gov (United States)

    Balogun, Amusa Saheed

    2010-12-01

    Some religious reactions to the HIV epidemic in Africa unwittingly contributed to the expansion of the epidemic in its early years. This was because many religious people regarded the emergence of HIV and AIDS as divine punishment for man's sins as a result of people's sexual promiscuity. Some also opposed public promotion of the use of condoms for HIV prevention. However, religious bodies have made positive contributions to HIV/AIDS responses in many African countries in recent times. Though Christian bodies are taking the lead in faith-based responses to HIV and AIDS in Africa, Islamic bodies have also been major partners in HIV/AIDS interventions in several countries. Against this background, this article examines some Islamic perceptions of HIV and AIDS, and especially the impact of antiretroviral treatment (ART) for people living with HIV in Africa, with particular emphasis on Nigeria. In spite of the emergence of antiretroviral (ARV) drugs in Africa, Islam still emphasises the prevention of new infections and care for people living with HIV or AIDS. The article discusses basic issues associated with ARVs, such as health, sickness, life-prolongation and death, from an Islamic viewpoint, as well as some Islamic measures to prevent HIV-risk-taking behaviours in an era of ARVs. It also looks at the nature and extent of Islamic involvement in the national HIV/AIDS response in Nigeria. The paper concludes that while Islam sees HIV and AIDS and other diseases as 'tests' from Allah, the religion is not opposed to ART. Thus, efforts need to be intensified by Islamic bodies and Muslim leaders in Nigeria for an improved response to HIV and AIDS in the country.

  1. The relationship of reported HIV risk and history of HIV testing among emergency department patients.

    Science.gov (United States)

    Merchant, Roland C; Freelove, Sarah M; Langan, Thomas J; Clark, Melissa A; Mayer, Kenneth H; Seage, George R; DeGruttola, Victor G

    2010-01-01

    Among a random sample of emergency department (ED) patients, we sought to determine the extent to which reported risk for human immunodeficiency virus (HIV) is related to ever having been tested for HIV. A random sample of patients (aged 18-64 years) from an adult, urban, northeastern United States, academic ED were surveyed about their history of ever having been tested for HIV and their reported HIV risk behaviors. A reported HIV risk score was calculated from the survey responses and divided into 4 levels, based on quartiles of the risk scores. Pearson's X(2) testing was used to compare HIV testing history and level of reported HIV risk. Logistic regression models were created to investigate the association between level of reported HIV risk and the outcome of ever having been tested for HIV. Of the 557 participants, 62.1% were female. A larger proportion of females than males (71.4% vs 60.6%; P history of injection-drug use, were associated with prior HIV testing for both genders. In the logistic regression analyses, there was no relationship between increasing level of reported HIV risk and a history of ever having been tested for HIV for males. For females, a history of ever having been tested was related to increasing level of reported risk, but not in a linear fashion. The relationship between reported HIV risk and history of testing among these ED patients was complex and differed by gender. Among these patients, having greater risk did not necessarily mean a higher likelihood of ever having been tested for HIV.

  2. Will the global HIV response fail gay and bisexual men and other men who have sex with men?

    Science.gov (United States)

    Ayala, George; Santos, Glenn-Milo

    2016-01-01

    Gay and bisexual men and other men who have sex with men are among the small number of groups for whom HIV remains uncontrolled worldwide. Although there have been recent and notable decreases in HIV incidence across several countries, prevalence and incidence is consistently higher or rising among men who have sex with men when compared with other groups. In 2014, MSMGF (the Global Forum on MSM & HIV) conducted its third biennial Global Men's Health and Rights Study, an international, multilingual, web-based cross-sectional survey of men who have sex with men recruited through online convenience sampling. We tested hypothesized correlates (selected a priori ) of successfully achieving each step along the HIV prevention and treatment continuum by fitting separate generalized estimating equation models adjusted for clustering by country in multivariate analyses. All models controlled for ability to meet basic financial needs, age, healthcare coverage, having a regular provider, region and country-level income. Higher provider discrimination and sexual stigma were associated with lower odds of perceived access to services, service utilization and virologic suppression. Conversely, accessing services from community-based organizations focused on lesbian, gay, bisexual and transgender people; greater engagement in gay community; and comfort with healthcare providers were associated with higher odds of achieving steps along the prevention and treatment continuum. To meet accelerated global HIV targets, global leaders must adopt a differentiated and bolder response, in keeping with current epidemiologic trends and community-based research. The HIV-related needs of gay and bisexual men and other men who have sex with men must be addressed openly, quickly and with sufficient resources to support evidence-based, community-led and human rights-affirming interventions at scale.

  3. An association between neighbourhood wealth inequality and HIV prevalence in sub-Saharan Africa.

    Science.gov (United States)

    Brodish, Paul Henry

    2015-05-01

    This paper investigates whether community-level wealth inequality predicts HIV serostatus using DHS household survey and HIV biomarker data for men and women ages 15-59 pooled from six sub-Saharan African countries with HIV prevalence rates exceeding 5%. The analysis relates the binary dependent variable HIV-positive serostatus and two weighted aggregate predictors generated from the DHS Wealth Index: the Gini coefficient, and the ratio of the wealth of households in the top 20% wealth quintile to that of those in the bottom 20%. In separate multilevel logistic regression models, wealth inequality is used to predict HIV prevalence within each statistical enumeration area, controlling for known individual-level demographic predictors of HIV serostatus. Potential individual-level sexual behaviour mediating variables are added to assess attenuation, and ordered logit models investigate whether the effect is mediated through extramarital sexual partnerships. Both the cluster-level wealth Gini coefficient and wealth ratio significantly predict positive HIV serostatus: a 1 point increase in the cluster-level Gini coefficient and in the cluster-level wealth ratio is associated with a 2.35 and 1.3 times increased likelihood of being HIV positive, respectively, controlling for individual-level demographic predictors, and associations are stronger in models including only males. Adding sexual behaviour variables attenuates the effects of both inequality measures. Reporting eleven plus lifetime sexual partners increases the odds of being HIV positive over five-fold. The likelihood of having more extramarital partners is significantly higher in clusters with greater wealth inequality measured by the wealth ratio. Disaggregating logit models by sex indicates important risk behaviour differences. Household wealth inequality within DHS clusters predicts HIV serostatus, and the relationship is partially mediated by more extramarital partners. These results emphasize the importance

  4. Relationship of race-, sexual orientation-, and HIV-related discrimination with adherence to HIV treatment: a pilot study.

    Science.gov (United States)

    Boarts, Jessica M; Bogart, Laura M; Tabak, Melanie A; Armelie, Aaron P; Delahanty, Douglas L

    2008-10-01

    Adherence to highly active antiretroviral therapy (HAART) must be close to perfect in order to maintain suppression of HIV viral load, and to prevent the development of drug resistant strains of HIV. People living with HIV (PLWH) often report low levels of adherence. One variable that has been linked to poor adherence is perceived discrimination; however, research has generally not considered the possible unique effects of different types of discrimination on adherence. The present pilot study aimed to examine the association of three types of discrimination (due to HIV+ status, race, or sexual orientation) with adherence among 57 PLWH. Logistic regression analyses were conducted to demonstrate the relationships between each type of discrimination and self-reported adherence. Racial discrimination significantly predicted lower adherence levels, whereas sexual orientation- and HIV-related discrimination did not. Results underscore the importance of addressing discrimination issues, specifically racial, when designing interventions to improve adherence to HAART.

  5. HIV-related stigma and optimism as predictors of anxiety and depression among HIV-positive men who have sex with men in the United Kingdom and Ireland.

    Science.gov (United States)

    Murphy, Patrick J; Garrido-Hernansaiz, Helena; Mulcahy, Fiona; Hevey, David

    2018-03-01

    This study investigated the associations between forms of HIV-related optimism, HIV-related stigma, and anxiety and depression among HIV-positive men who have sex with men (MSM) in the United Kingdom and Ireland. HIV health optimism (HHO) and HIV transmission optimism (HTO) were hypothesised to be protective factors for anxiety and depression, while the components of HIV-related stigma (enacted stigma, disclosure concerns, concern with public attitudes, and internalised stigma) were hypothesised to be risk factors. Data were collected from 278 HIV-positive MSM using an online questionnaire. The prevalence of psychological distress was high, with close to half (48.9%) of all participants reporting symptoms of anxiety, and more than half (57.9%) reporting symptoms of depression. Multiple linear regressions revealed that both anxiety and depression were positively predicted by internalised stigma and enacted stigma, and negatively predicted by HHO. For both anxiety and depression, internalised stigma was the strongest and most significant predictor. The results highlight the continued psychological burden associated with HIV infection among MSM, even as community support services are being defunded across the United Kingdom and Ireland. The results point to the need for clinicians and policy makers to implement stigma reduction interventions among this population.

  6. Role of T. cruzi exposure in the pattern of T cell cytokines among chronically infected HIV and Chagas disease patients

    Directory of Open Access Journals (Sweden)

    Tania Regina Tozetto-Mendoza

    Full Text Available OBJECTIVES: The impact of Chagas disease (CD in HIV-infected patients is relevant throughout the world. In fact, the characterization of the adaptive immune response in the context of co-infection is important for predicting the need for interventions in areas in which HIV and Chagas disease co-exist. METHODS: We described and compared the frequency of cytokine-producing T cells stimulated with soluble antigen of Trypanosoma cruzi (T. cruzi using a cytometric assay for the following groups: individuals with chronic Chagas disease (CHR, n=10, those with Chagas disease and HIV infection (CO, n=11, those with only HIV (HIV, n=14 and healthy individuals (C, n=15. RESULTS: We found 1 a constitutively lower frequency of IL-2+ and IFN-γ+ T cells in the CHR group compared with the HIV, CO and healthy groups; 2 a suppressive activity of soluble T. cruzi antigen, which down-regulated IL-2+CD4+ and IFN-γ+CD4+ phenotypes, notably in the healthy group; 3 a down-regulation of inflammatory cytokines on CD8+ T cells in the indeterminate form of Chagas disease; and 4 a significant increase in IL-10+CD8+ cells distinguishing the indeterminate form from the cardiac/digestive form of Chagas disease, even in the presence of HIV infection. CONCLUSIONS: Taken together, our data suggest the presence of an immunoregulatory response in chronic Chagas disease, which seems to be driven by T. cruzi antigens. Our findings provide new insights into immunotherapeutic strategies for people living with HIV/AIDS and Chagas disease.

  7. Persistence of hepatitis A virus antibodies after primary immunization and response to revaccination in children and adolescents with perinatal HIV exposure

    Science.gov (United States)

    Gouvêa, Aída de Fátima Thomé Barbosa; Pinto, Maria Isabel de Moraes; Miyamoto, Maristela; Machado, Daisy Maria; Pessoa, Silvana Duarte; do Carmo, Fabiana Bononi; Beltrão, Suênia Cordeiro de Vasconcelos; Succi, Regina Célia de Menezes

    2015-01-01

    OBJECTIVE: To assess possible factors associated with the loss of antibodies to hepatitis A 7 years after the primary immunization in children of HIV-infected mothers and the response to revaccination in patients seronegative for hepatitis A. METHODS: Quantification of HAV antibodies by electrochemiluminescence was performed in 39 adolescents followed up at the Pediatric Aids Clinic of Federal University of São Paulo (Unifesp): 29 HIV-infected (HIV group) (median age: 12.8 years) and 10 HIV-exposed but non-infected (ENI group) (median age: 13.4 years). All of them received two doses of HAV vaccine (Havrix(r)) in 2002. RESULTS: The median age at primary immunization (PI) was 5.4 years for HIV group and 6.5 years for ENI group. All children, from both groups, had antibodies to HAV >20 mIU/mL after PI. Seven years later, the ENI group showed a median concentration of antibodies = 253.5 mIU/mL, while the HIV group = 113.0 mIU/mL (Mann-Whitney test, p=0.085). All ENI group and 23/29 (79.3%) from HIV group mantained HAV antibodies 7 years after PI. The levels of hepatitis A antibodies in the primary vaccination were the only factor independently associated with maintaining these antibodies for 7 years. The group that lost HAV seropositivity was revaccinated and 83.3% (5/6) responded with antibodies >20 mUI/mL. CONCLUSIONS: The antibodies levels acquired in the primary vaccination in the HIV group were the main factor associated with antibodies loss after HAV immunization. PMID:25918013

  8. Attenuation of Pathogenic Immune Responses during Infection with Human and Simian Immunodeficiency Virus (HIV/SIV) by the Tetracycline Derivative Minocycline

    Science.gov (United States)

    Drewes, Julia L.; Szeto, Gregory L.; Engle, Elizabeth L.; Liao, Zhaohao; Shearer, Gene M.; Zink, M. Christine; Graham, David R.

    2014-01-01

    HIV immune pathogenesis is postulated to involve two major mechanisms: 1) chronic innate immune responses that drive T cell activation and apoptosis and 2) induction of immune regulators that suppress T cell function and proliferation. Both arms are elevated chronically in lymphoid tissues of non-natural hosts, which ultimately develop AIDS. However, these mechanisms are not elevated chronically in natural hosts of SIV infection that avert immune pathogenesis despite similarly high viral loads. In this study we investigated whether minocycline could modulate these pathogenic antiviral responses in non-natural hosts of HIV and SIV. We found that minocycline attenuated in vitro induction of type I interferon (IFN) and the IFN-stimulated genes indoleamine 2,3-dioxygenase (IDO1) and TNF-related apoptosis inducing ligand (TRAIL) in human plasmacytoid dendritic cells and PBMCs exposed to aldrithiol-2 inactivated HIV or infectious influenza virus. Activation-induced TRAIL and expression of cytotoxic T-lymphocyte antigen 4 (CTLA-4) in isolated CD4+ T cells were also reduced by minocycline. Translation of these in vitro findings to in vivo effects, however, were mixed as minocycline significantly reduced markers of activation and activation-induced cell death (CD25, Fas, caspase-3) but did not affect expression of IFNβ or the IFN-stimulated genes IDO1, FasL, or Mx in the spleens of chronically SIV-infected pigtailed macaques. TRAIL expression, reflecting the mixed effects of minocycline on activation and type I IFN stimuli, was reduced by half, but this change was not significant. These results show that minocycline administered after infection may protect against aspects of activation-induced cell death during HIV/SIV immune disease, but that in vitro effects of minocycline on type I IFN responses are not recapitulated in a rapid progressor model in vivo. PMID:24732038

  9. recommendations for completing death notification forms in hiv

    African Journals Online (AJOL)

    2008-10-14

    Oct 14, 2008 ... (including tuberculosis and respiratory diseases) with age-specific death rates for HIV as predicted by the. Actuarial Society of South Africa model (ASSA 2000), and observed a high level of correlation, concluding that these diseases account for the 'missing' HIV cause of death statistics, and showing that ...

  10. Metabolomics biomarkers to predict acamprosate treatment response in alcohol-dependent subjects.

    Science.gov (United States)

    Hinton, David J; Vázquez, Marely Santiago; Geske, Jennifer R; Hitschfeld, Mario J; Ho, Ada M C; Karpyak, Victor M; Biernacka, Joanna M; Choi, Doo-Sup

    2017-05-31

    Precision medicine for alcohol use disorder (AUD) allows optimal treatment of the right patient with the right drug at the right time. Here, we generated multivariable models incorporating clinical information and serum metabolite levels to predict acamprosate treatment response. The sample of 120 patients was randomly split into a training set (n = 80) and test set (n = 40) five independent times. Treatment response was defined as complete abstinence (no alcohol consumption during 3 months of acamprosate treatment) while nonresponse was defined as any alcohol consumption during this period. In each of the five training sets, we built a predictive model using a least absolute shrinkage and section operator (LASSO) penalized selection method and then evaluated the predictive performance of each model in the corresponding test set. The models predicted acamprosate treatment response with a mean sensitivity and specificity in the test sets of 0.83 and 0.31, respectively, suggesting our model performed well at predicting responders, but not non-responders (i.e. many non-responders were predicted to respond). Studies with larger sample sizes and additional biomarkers will expand the clinical utility of predictive algorithms for pharmaceutical response in AUD.

  11. An observation on the variance of a predicted response in ...

    African Journals Online (AJOL)

    ... these properties and computational simplicity. To avoid over fitting, along with the obvious advantage of having a simpler equation, it is shown that the addition of a variable to a regression equation does not reduce the variance of a predicted response. Key words: Linear regression; Partitioned matrix; Predicted response ...

  12. HIV Risk Characteristics Associated with Violence Against Women: A Longitudinal Study Among Women in the United States.

    Science.gov (United States)

    Montgomery, Brooke E E; Frew, Paula M; Hughes, James P; Wang, Jing; Adimora, Adaora A; Haley, Danielle F; Kuo, Irene; Jennings, Larissa; El-Bassel, Nabila; Hodder, Sally L

    2018-06-15

    Using data from HIV Prevention Trials Network 064, a multisite, observational cohort study conducted to estimate HIV incidence rates among women living in areas of high poverty and HIV prevalence in the United States, we examined the use of HIV risk characteristics to predict emotional abuse, physical violence, and forced sex. Participants included 2099 women, 18-44 years of age, who reported unprotected vaginal or anal sex with a male partner and an additional personal or perceived male partner HIV risk characteristic in the past 6 months. Adjusting for time-varying covariates, generalized estimating equations were used to assess the ability of HIV risk characteristics to predict violence 6 months later. Reported analyses were limited to the 1980 study participants who reported having a male sex partner at that assessment. Exchanging sex, perceived partner concurrency, and perceived partner incarceration were significantly predictive of emotional abuse 6 months later (adjusted odds ratio [AOR]: 1.60; 1.59; 1.34, respectively). Prior sexually transmitted infection diagnosis, exchanging sex, and binge drinking were significantly predictive of physical violence 6 months later (AOR: 1.62; 1.71; 1.47, respectively). None of the variables measured was significantly predictive of forced sex. Strategies that address reducing violence against women should be studied further in the context of HIV prevention programs.

  13. Influential Factors for Accurate Load Prediction in a Demand Response Context

    DEFF Research Database (Denmark)

    Wollsen, Morten Gill; Kjærgaard, Mikkel Baun; Jørgensen, Bo Nørregaard

    2016-01-01

    Accurate prediction of a buildings electricity load is crucial to respond to Demand Response events with an assessable load change. However, previous work on load prediction lacks to consider a wider set of possible data sources. In this paper we study different data scenarios to map the influence....... Next, the time of day that is being predicted greatly influence the prediction which is related to the weather pattern. By presenting these results we hope to improve the modeling of building loads and algorithms for Demand Response planning.......Accurate prediction of a buildings electricity load is crucial to respond to Demand Response events with an assessable load change. However, previous work on load prediction lacks to consider a wider set of possible data sources. In this paper we study different data scenarios to map the influence...

  14. Prevalence of HIV/AIDS and prediction of future trends in north-west region of India: A six-year ICTC-based study

    Directory of Open Access Journals (Sweden)

    Vyas Nitya

    2009-01-01

    Full Text Available Background: The study was conducted to analyze previous six-year prevalence data of HIV infection in the Northwest region of India and predict future trends for a couple of years. Objectives: The study was conducted to aid SACS and NACO to plan and arrange resources for the future scenario. Materials and Methods: All the attendees of ICTC, Jaipur, from January 2002 to December 2007 were included and variables like age, sex, marital status, occupation, place of residence, pattern of risk behavior and HIV serostatus were studied. As per the strategy and policy prescribed by NACO, tests (E/R/S were performed on the serum samples. Data was collected; compiled and analyzed using standard statistical methods. Future trends of HIV-prevalence in north-west India were anticipated. Results: The overall positivity rates among attendees of ICTC, were found to be 12.2% (386/3161, 11.8% (519/4381, 11.1% (649/5867, 13% (908/6983, 14% (1385/9911 and 17.34% (1756/10133 in the years 2002, 2003, 2004, 2005, 2006 and 2007 respectively. Future trends for the next couple of years depict further increase in prevalence without any plateau. Conclusion: Epidemiological studies should be carried out in various settings to understand the role and complex relations of innumerable behavioral, social and demographic factors, which will help, interrupt and control the transmission of HIV/ AIDS.

  15. Assessing Prediction Performance of Neoadjuvant Chemotherapy Response in Bladder Cancer

    OpenAIRE

    Cremer, Chris

    2016-01-01

    Neoadjuvant chemotherapy is a treatment routinely prescribed to patients diagnosed with muscle-invasive bladder cancer. Unfortunately, not all patients are responsive to this treatment and would greatly benefit from an accurate prediction of their expected response to chemotherapy. In this project, I attempt to develop a model that will predict response using tumour microarray data. I show that using my dataset, every method is insufficient at accurately classifying responders and non-respond...

  16. Patients with discordant responses to antiretroviral therapy have impaired killing of HIV-infected T cells.

    Directory of Open Access Journals (Sweden)

    Sekar Natesampillai

    2010-11-01

    Full Text Available In medicine, understanding the pathophysiologic basis of exceptional circumstances has led to an enhanced understanding of biology. We have studied the circumstance of HIV-infected patients in whom antiretroviral therapy results in immunologic benefit, despite virologic failure. In such patients, two protease mutations, I54V and V82A, occur more frequently. Expressing HIV protease containing these mutations resulted in less cell death, caspase activation, and nuclear fragmentation than wild type (WT HIV protease or HIV protease containing other mutations. The impaired induction of cell death was also associated with impaired cleavage of procaspase 8, a requisite event for HIV protease mediated cell death. Primary CD4 T cells expressing I54V or V82A protease underwent less cell death than with WT or other mutant proteases. Human T cells infected with HIV containing these mutations underwent less cell death and less Casp8p41 production than WT or HIV containing other protease mutations, despite similar degrees of viral replication. The reductions in cell death occurred both within infected cells, as well as in uninfected bystander cells. These data indicate that single point mutations within HIV protease which are selected in vivo can significantly impact the ability of HIV to kill CD4 T cells, while not impacting viral replication. Therefore, HIV protease regulates both HIV replication as well as HIV induced T cell depletion, the hallmark of HIV pathogenesis.

  17. Predicting the Onset of Sexual and Drug Risk Behaviors in HIV-Negative Youths with HIV-Positive Mothers: The Role of Contextual, Self-Regulation, and Social-Interaction Factors

    Science.gov (United States)

    Mellins, Claude A.; Dolezal, Curtis; Brackis-Cott, Elizabeth; Nicholson, Ouzama; Warne, Patricia; Meyer-Bahlburg, Heino F. L.

    2007-01-01

    HIV-negative, inner-city adolescents with HIV-infected parents are considered to be at high risk for acquiring HIV themselves. Using a modified theory of health behavior, this study examined the effects of maternal HIV infection and psychosocial variables on the onset of sexual and drug risk behavior in 144 HIV-negative adolescents with and…

  18. Loss to Follow-Up Among HIV-Exposed Children in an HIV Clinic in Beira, Mozambique

    Directory of Open Access Journals (Sweden)

    Ana Judith Blanco

    2015-07-01

    Full Text Available Loss to follow-up contributes to the low coverage of HIV care interventions among HIV-exposed infants in Beira, Mozambique. This qualitative study explores the perceptions of HIV-infected women and their health care providers regarding the main obstacles preventing women from attending follow-up visits for HIV care, and factors influencing women’s decisions about newborn care. Fifty-two in-depth interviews and two focus group discussions were conducted; transcripts were coded and analyzed using ATLAS.ti. Interviewees perceived three major barriers to follow-up: food insecurity, difficulties navigating the health system, and women’s familial roles and responsibilities. Our findings unveil the complex context in which HIV-infected women and their children live, and suggest that the structure and function of the HIV care system should be reviewed. Economic empowerment of women is crucial to achieving better compliance with medical care. Integration of mother and child services and more efficient and culturally sensitive medical services may improve follow-up.

  19. Striatal Activation Predicts Differential Therapeutic Responses to Methylphenidate and Atomoxetine.

    Science.gov (United States)

    Schulz, Kurt P; Bédard, Anne-Claude V; Fan, Jin; Hildebrandt, Thomas B; Stein, Mark A; Ivanov, Iliyan; Halperin, Jeffrey M; Newcorn, Jeffrey H

    2017-07-01

    Methylphenidate has prominent effects in the dopamine-rich striatum that are absent for the selective norepinephrine transporter inhibitor atomoxetine. This study tested whether baseline striatal activation would predict differential response to the two medications in youth with attention-deficit/hyperactivity disorder (ADHD). A total of 36 youth with ADHD performed a Go/No-Go test during functional magnetic resonance imaging at baseline and were treated with methylphenidate and atomoxetine using a randomized cross-over design. Whole-brain task-related activation was regressed on clinical response. Task-related activation in right caudate nucleus was predicted by an interaction of clinical responses to methylphenidate and atomoxetine (F 1,30  = 17.00; p atomoxetine. The rate of robust response was higher for methylphenidate than for atomoxetine in youth with high (94.4% vs. 38.8%; p = .003; number needed to treat = 2, 95% CI = 1.31-3.73) but not low (33.3% vs. 50.0%; p = .375) caudate activation. Furthermore, response to atomoxetine predicted motor cortex activation (F 1,30  = 14.99; p atomoxetine in youth with ADHD, purportedly reflecting the dopaminergic effects of methylphenidate but not atomoxetine in the striatum, whereas motor cortex activation may predict response to atomoxetine. These data do not yet translate directly to the clinical setting, but the approach is potentially important for informing future research and illustrates that it may be possible to predict differential treatment response using a biomarker-driven approach. Stimulant Versus Nonstimulant Medication for Attention Deficit Hyperactivity Disorder in Children; https://clinicaltrials.gov/; NCT00183391. Copyright © 2017 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.

  20. Masculinity and HIV disclosure among heterosexual South African men: implications for HIV/AIDS intervention.

    Science.gov (United States)

    Dageid, Wenche; Govender, Kaymarlin; Gordon, Sarah F

    2012-01-01

    Relationships and constructions of masculinity are central to understanding the process of male HIV disclosure, which is an important step towards accessing HIV-related services. Data from in-depth interviews and focus-group discussions with 23 HIV-positive, self-identified heterosexual, Black South African men were used to explore the disclosure process and how this process was negotiated in the context of constructions of masculinity. Of these men, 20 had disclosed to one or more persons, with partners and siblings being the preferred confidants. Disclosure was dependent on the acceptance of HIV status, perceived support and healthy relationships with others, HIV counselling and participation in educational and training activities. Non-disclosure was explained as a result of stigma, fear of rejection, discrimination, a lack of healthy relationships with others and lack of access to suitable disclosure strategies. Negative perceptions of HIV and hegemonic conceptions of masculinity hindered men from disclosing and seeking health services. Many men, however, managed to renegotiate their masculine identities to become responsible, knowledgeable HIV-positive individuals, protecting their families and becoming community educators. Findings suggest the need to consider gendered, contextual, skills-building/income-generating and guided interventions to promote male HIV disclosure and service uptake.