HIV-infected sex workers with beneficial HLA-variants are potential hubs for selection of HIV-1 recombinants that may affect disease progression.
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ABSTRACT:
SUBMITTER: Chang CH
PROVIDER: S-EPMC4469978 | biostudies-literature | 2015 Jun
REPOSITORIES: biostudies-literature
Publications
HIV-infected sex workers with beneficial HLA-variants are potential hubs for selection of HIV-1 recombinants that may affect disease progression.
Chang Chih-Hao CH Kist Nicolaas C NC Stuart Chester Tammy L TL Sreenu Vattipally B VB Herman Melissa M Luo Ma M Lunn Daniel D Bell John J Plummer Francis A FA Ball T Blake TB Katzourakis Aris A Iversen Astrid K N AK
Scientific reports 20150617
Cytotoxic T lymphocyte (CTL) responses against the HIV Gag protein are associated with lowering viremia; however, immune control is undermined by viral escape mutations. The rapid viral mutation rate is a key factor, but recombination may also contribute. We hypothesized that CTL responses drive the outgrowth of unique intra-patient HIV-recombinants (URFs) and examined gag sequences from a Kenyan sex worker cohort. We determined whether patients with HLA variants associated with effective CTL re ...[more]
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Project description:BACKGROUND:HIV diagnosis, the first step in HIV care and treatment engagement, may be inhibited by substance use among female sex workers (FSW). We assessed the relationship between alcohol and cannabis use and lack of HIV infection awareness among HIV-infected FSW in Lilongwe, Malawi. METHODS:From July to September, 2014, 200 FSW aged ?18 years were enrolled using venue-based sampling to examine substance use, HIV testing history, and serostatus ascertained by HIV rapid test. We used Poisson regression with robust variance estimates to estimate the associations of alcohol and cannabis use and lack of HIV infection awareness. RESULTS:Of the 138 HIV-infected FSW, 20% were unaware of their HIV infection, with 70% not testing within 6 months prior. According to the Alcohol Use Disorder Identification Tests (AUDIT), 55% of FSW unaware of their HIV infection reported hazardous, harmful, or dependent alcohol consumption. We observed a dose-response relationship between alcohol use and lack of HIV infection awareness, with alcohol dependency significantly associated with lack of HIV infection awareness (adjusted prevalence ratio: 3.0, 95% CI: 1.3, 6.8). Current cannabis use was uncommon (26%) among unaware HIV-infected FSW and weakly associated with lack of HIV infection awareness adjusted prevalence ratio: 1.1, 95% CI: 0.5, 2.5). CONCLUSION:Increased levels of alcohol use is associated with lack of HIV infection awareness among HIV-infected FSW in Malawi. Frequent, consistent HIV testing integrated with alcohol reduction strategies could improve the health and infection awareness of substance-using FSW.
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Project description:PurposeWe aimed to characterize the antiretroviral therapy (ART) cascade among female sex workers (FSWs) globally.MethodsWe systematically searched PubMed, Embase and MEDLINE in March 2014 to identify studies reporting on ART uptake, attrition, adherence, and outcomes (viral suppression or CD4 count improvements) among HIV-infected FSWs globally. When possible, available estimates were pooled using random effects meta-analyses (with heterogeneity assessed using Cochran's Q test and I2 statistic).Results39 studies, reporting on 21 different FSW study populations in Asia, Africa, North America, South America, and Central America and the Caribbean, were included. Current ART use among HIV-infected FSWs was 38% (95% CI: 29%-48%, I2?=?96%, 15 studies), and estimates were similar between high-, and low- and middle-income countries. Ever ART use among HIV-infected FSWs was greater in high-income countries (80%; 95% CI: 48%-94%, I2?=?70%, 2 studies) compared to low- and middle-income countries (36%; 95% CI: 7%-81%, I2?=?99%, 3 studies). Loss to follow-up after ART initiation was 6% (95% CI: 3%-11%, I2?=?0%, 3 studies) and death after ART initiation was 6% (95% CI: 3%-11%, I2?=?0%, 3 studies). The fraction adherent to ?95% of prescribed pills was 76% (95% CI: 68%-83%, I2?=?36%, 4 studies), and 57% (95% CI: 46%-68%, I2?=?82%, 4 studies) of FSWs on ART were virally suppressed. Median gains in CD4 count after 6 to 36 months on ART, ranged between 103 and 241 cells/mm3 (4 studies).ConclusionsDespite global increases in ART coverage, there is a concerning lack of published data on HIV treatment for FSWs. Available data suggest that FSWs can achieve levels of ART uptake, retention, adherence, and treatment response comparable to that seen among women in the general population, but these data are from only a few research settings. More routine programme data on HIV treatment among FSWs across settings should be collected and disseminated.
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Project description:The genetic polymorphism that has the greatest impact on immune control of human immunodeficiency virus (HIV) infection is expression of HLA-B*57. Understanding of the mechanism for this strong effect remains incomplete. HLA-B*57 alleles and the closely related HLA-B*5801 are often grouped together because of their similar peptide-binding motifs and HIV disease outcome associations. However, we show here that the apparently small differences between HLA-B*57 alleles, termed HLA-B*57 micropolymorphisms, have a significant impact on immune control of HIV. In a study cohort of >2,000 HIV C-clade-infected subjects from southern Africa, HLA-B*5703 is associated with a lower viral-load set point than HLA-B*5702 and HLA-B*5801 (medians, 5,980, 15,190, and 19,000 HIV copies/ml plasma; P = 0.24 and P = 0.0005). In order to better understand these observed differences in HLA-B*57/5801-mediated immune control of HIV, we undertook, in a study of >1,000 C-clade-infected subjects, a comprehensive analysis of the epitopes presented by these 3 alleles and of the selection pressure imposed on HIV by each response. In contrast to previous studies, we show that each of these three HLA alleles is characterized both by unique CD8(+) T-cell specificities and by clear-cut differences in selection pressure imposed on the virus by those responses. These studies comprehensively define for the first time the CD8(+) T-cell responses and immune selection pressures for which these protective alleles are responsible. These findings are consistent with HLA class I alleles mediating effective immune control of HIV through the number of p24 Gag-specific CD8(+) T-cell responses generated that can drive significant selection pressure on the virus.
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Project description:Worldwide, transgender women who engage in sex work have a disproportionate risk for HIV compared with natal male and female sex workers. We reviewed recent epidemiological research on HIV in transgender women and show that transgender women sex workers (TSW) face unique structural, interpersonal, and individual vulnerabilities that contribute to risk for HIV. Only six studies of evidence-based prevention interventions were identified, none of which focused exclusively on TSW. We developed a deterministic model based on findings related to HIV risks and interventions. The model examines HIV prevention approaches in TSW in two settings (Lima, Peru and San Francisco, CA, USA) to identify which interventions would probably achieve the UN goal of 50% reduction in HIV incidence in 10 years. A combination of interventions that achieves small changes in behaviour and low coverage of biomedical interventions was promising in both settings, suggesting that the expansion of prevention services in TSW would be highly effective. However, this expansion needs appropriate sustainable interventions to tackle the upstream drivers of HIV risk and successfully reach this population. Case studies of six countries show context-specific issues that should inform development and implementation of key interventions across heterogeneous settings. We summarise the evidence and knowledge gaps that affect the HIV epidemic in TSW, and propose a research agenda to improve HIV services and policies for this population.
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Project description:BACKGROUND:Despite recent progress, there exist gaps in the prevention of vertical HIV transmission program access and uptake in Cameroon. Female sex workers (FSW), many of whom are mothers, are disproportionately affected by HIV and have specific barriers to HIV testing and treatment access. Testing for HIV-exposed infants is crucial in monitoring for incident infection and timely intervention. This study explores the level of early childhood testing and also associations between antenatal care (ANC) attendance and other factors and early childhood HIV testing among FSW in Cameroon. METHODS:FSW were recruited to participate in an integrated biobehavioral survey in Cameroon between December 2015 and October 2016. Women were included in these analyses if they were living with HIV and had at least one living child. Both univariate and multivariable logistic regression were used to look at predictors of a child being tested for HIV before age five. RESULTS:A total of 481/2255 FSW were eligible for these analyses as they were HIV seropositive and had at least one living child at the time of the study. Women included in these analyses had a median age of 35(IQR 30-41). Nearly 70% reported none of their children had been tested for HIV before age five (326/481), and 3.5%(17/481) reported one or more of their children had been diagnosed with HIV. ANC attendance (adjusted OR 2.12, 95% CI: [1.02, 4.55]), awareness of HIV status (aOR 3.70[2.30, 5.93]), pregnancy intentions (aOR 1.89[1.16, 3.08]), and higher education (aOR 2.17[1.01, 4.71]) were all independently associated with increased odds of women having a greater proportion of children tested for HIV before age five. Regional differences in early childhood testing were also observed. CONCLUSION:Vertical transmission of HIV remains a challenge in Cameroon, and HIV testing among children of FSW living with HIV was very low. ANC attendance and promotion of the mother's health were associated with increased child HIV testing. For women at high risk of HIV and for whom engagement in the health system is low, strategies to promote and ensure ANC attendance are essential for their health and the health of their children.
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Project description:Globally HIV incidence is slowing, however HIV epidemics among sex workers are stable or increasing in many settings. While laws governing sex work are considered structural determinants of HIV, individual-level data assessing this relationship are limited. In this study, individual-level data are used to assess the relationships of sex work laws and stigmas in increasing HIV risk among female sex workers, and examine the mechanisms by which stigma affects HIV across diverse legal contexts in countries across sub-Saharan Africa. Interviewer-administered socio-behavioral questionnaires and biological testing were conducted with 7259 female sex workers between 2011-2018 across 10 sub-Saharan African countries. These data suggest that increasingly punitive and non-protective laws are associated with prevalent HIV infection and that stigmas and sex work laws may synergistically increase HIV risks. Taken together, these data highlight the fundamental role of evidence-based and human-rights affirming policies towards sex work as part of an effective HIV response.
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Project description:Female, male, and transgender sex workers continue to have disproportionately high burdens of HIV infection in low-income, middle-income, and high-income countries in 2018. 4 years since our Lancet Series on HIV and sex work, our updated analysis of the global HIV burden among female sex workers shows that HIV prevalence is unacceptably high at 10·4% (95% CI 9·5-11·5) and is largely unchanged. Comprehensive epidemiological data on HIV and antiretroviral therapy (ART) coverage are scarce, particularly among transgender women. Sustained coverage of treatment is markedly uneven and challenged by lack of progress on stigma and criminalisation, and sustained human rights violations. Although important progress has been made in biomedical interventions with pre-exposure prophylaxis and early ART feasibility and demonstration projects, limited coverage and retention suggest that sustained investment in community and structural interventions is required for sex workers to benefit from the preventive interventions and treatments that other key populations have. Evidence-based progress on full decriminalisation grounded in health and human rights-a key recommendation in our Lancet Series-has stalled, with South Africa a notable exception. Additionally, several countries have rolled back rights to sex workers further. Removal of legal barriers through the decriminalisation of sex work, alongside political and funding investments to support community and structural interventions, is urgently needed to reverse the HIV trajectory and ensure health and human rights for all sex workers.
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