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Genetic correlates influencing immunopathogenesis of HIV infection.

ABSTRACT: Variability to HIV infection, its progression as well as responsiveness to antiretroviral therapy (ART) is observed among individuals including viraemia controllers or exposed uninfected, rapid versus slow progressors and ART responders compared to non responders. This differential responsiveness/vulnerability to HIV-1 is governed by multiple host genetic factors that include HLA, cytokines, chemokines, their receptors and others. This review highlights the influence of these genetic factors on HIV/AIDS outcome; however, in India, the information in this area is very limited and most of these genetic studies have been conducted in Caucasian and South African populations. Considering the population-specific differences in the frequencies of protective or susceptibility favouring alleles and their influence on the disease outcome, it is of utmost importance to strengthen ongoing efforts towards defining largely unknown genetic propensity in Indian population, particularly by recruitment of large cohorts of well categorized exposed uninfected individuals, rapid, long term non progressors and elite viraemic controllers. Multi-parametric analysis of these potentially interactive immunogenetic variables in these cohorts may help to define potential targets for diagnostics and therapy in a population specific manner.

SUBMITTER: Sharma G

PROVIDER: S-EPMC3284087 | biostudies-literature | 2011 Dec

REPOSITORIES: biostudies-literature

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Genetic correlates influencing immunopathogenesis of HIV infection.

Sharma Gaurav G Kaur Gurvinder G Mehra Narinder N

The Indian journal of medical research 20111201 6

Variability to HIV infection, its progression as well as responsiveness to antiretroviral therapy (ART) is observed among individuals including viraemia controllers or exposed uninfected, rapid versus slow progressors and ART responders compared to non responders. This differential responsiveness/vulnerability to HIV-1 is governed by multiple host genetic factors that include HLA, cytokines, chemokines, their receptors and others. This review highlights the influence of these genetic factors on ...[more]

PMID: 22310811

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Project description:Genetic and immunologic analyses of epidemiologically-linked HIV transmission enable insights into the impact of immune responses on clinical outcomes. Human vaccine trials and animal studies of HIV-1 infection have suggested immune correlates of protection; however, their role in natural infection in terms of protection from disease progression is mostly unknown. Four HIV-1+ Cameroonian individuals, three of them epidemiologically-linked in a polygamous heterosexual relationship and one incidence-matched case, were studied over 15 years for heterologous and cross-neutralizing antibody responses, antibody binding, IgA/IgG levels, antibody-dependent cellular cytotoxicity (ADCC) against cells expressing wild-type or CD4-bound Env, viral evolution, Env epitopes, and host factors including HLA-I alleles. Despite viral infection with related strains, the members of the transmission cluster experienced contrasting clinical outcomes including cases of rapid progression and long-term non-progression in the absence of strongly protective HLA-I or CCR5Δ32 alleles. Slower progression and higher CD4/CD8 ratios were associated with enhanced IgG antibody binding to native Env and stronger V1V2 antibody binding responses in the presence of viruses with residue K169 in V2. ADCC against cells expressing Env in the CD4-bound conformation in combination with low Env-specific IgA/IgG ratios correlated with better clinical outcome. This data set highlights for the first time that V1V2-directed antibody responses and ADCC against cells expressing open, CD4-exposed Env, in the presence of low plasma IgA/IgG ratios, can correlate with clinical outcome in natural infection. These parameters are comparable to the major correlates of protection, identified post-hoc in the RV144 vaccine trial; thus, they may also modulate the rate of clinical progression once infected. The findings illustrate the potential of immune correlate analysis in natural infection to guide vaccine development.

Project description:BackgroundIn an era when HIV transmission has been on the rise among men who have sex with men (MSM), transgender women may play a considerable role in China's current HIV epidemic as a potential "bridge" of HIV transmission between homosexual and heterosexual populations. We sought to understand the risk behaviours and factors associated with HIV infection among transgender women in two cities in China.MethodsFrom January to December 2016, we recruited transgender women with the help of community-based organizations (CBOs) through a wide range of methods, including snowball sampling. After recruitment, we asked participants to fill out a structured questionnaire including questions about socio-demographics, sexual behaviours, condom use, substance use and uptake of health care services. HIV infection status was determined by using two different rapid testing reagents.ResultsAmong 498 subjects enrolled in this study, 233 were from Shanghai and 265 were from Tianjin. The median age was 30 years (range: 18-68; IQR: 24-33). Of them, 337 (67.7%) preferred feminine dress, 13 (2.6%) had undergone transsexual operation and 68 (13.7%) had used hormones for transition purposes. Nearly half (45.6%) reported having regular partners, and 351 (70.5%) had casual partners. Regarding condom use, 81.5% reported not always using condoms with stable partners, and 70.9% reported not using condoms with casual partners. Twenty-five (5.0%) had a history of buying sex and fifty-one (10.2%) had a history of selling sex in the past three months. A total of 200 (40.2%) participants had used at least one kind of controlled substance in the past six months. The most commonly used substances were amyl nitrates (rush popper) (99.5%) and 5-MeO-DiPT (20.0%). Among rush popper users, 170 (85.4%) reported always having sex while on the drug, and 177 (88.9%) reported increased sexual pleasure after using the drug. The HIV infection risk factors identified in our study were being located in Shanghai (aOR = 9.35, 95% CI = 3.89-22.49), selling sex in the past three months (aOR = 3.44, 95% CI = 1.31-9.01), and substance use in the past six months (aOR = 5.71, 95% CI = 2.63-12.41).ConclusionsTransgender women bear a high HIV burden in the two Chinese cities. Those involved in commercial sex tended to have inconsistent condom use, leading to high risk of HIV infection. Substance use was an independent risk factor of HIV infection by increasing sexual activities and unprotected sex, which indicated an aggravated and complex situation with possible interacting syndemic factors that could cumulatively facilitate sexual risk behaviours and HIV infection in transgender women. There is an urgent need for innovative and appropriate HIV prevention programmes targeting this unique population. Efforts should be made to provide them with tailored services including persuasive communication on consistent condom use, substance use counselling and related referral services, all with the goal of reducing HIV epidemic among transgender women.

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Genetic correlates influencing immunopathogenesis of HIV infection.

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Genetic correlates influencing immunopathogenesis of HIV infection.

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