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:BackgroundHIV 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.MethodsFrom 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.ResultsOf 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).ConclusionIncreased 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.
| S-EPMC4829472 | biostudies-literature
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.
| S-EPMC4179256 | biostudies-literature
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.
| S-EPMC3255844 | biostudies-other
Project description:BackgroundMost HIV infections are transmitted across mucosal epithelium. Understanding the role of innate and specific mucosal immunity in susceptibility or protection against HIV infection, as well as the effect of HIV infection on mucosal immunity, are of fundamental importance. HLA-G is a powerful modulator of the immune response. The aim of this study was to investigate whether soluble HLA-G (sHLA-G) expression in the female genital tract is associated with HIV-1 infection.Methods and findingsGenital levels of sHLA-G were determined in 52 HIV-1-uninfected and 44 antiretroviral naïve HIV-1-infected female commercial sex workers (CSWs), as well as 71 HIV-1-uninfected non-CSW women at low risk of exposure, recruited in Cotonou, Benin. HIV-1-infected CSWs had higher genital levels of sHLA-G compared with those in both the HIV-1-uninfected CSW (P?=?0.009) and non-CSW groups (P?=?0.0006). The presence of bacterial vaginosis (P?=?0.008), and HLA-G*01:01:02 genotype (P?=?0.002) were associated with higher genital levels of sHLA-G in the HIV-1-infected CSWs, whereas the HLA-G*01:04:04 genotype was also associated with higher genital level of sHLA-G in the overall population (P?=?0.038). When adjustment was made for all significant variables, the increased expression of sHLA-G in the genital mucosa remained significantly associated with both HIV-1 infection (P?=?0.02) and bacterial vaginosis (P?=?0.03).ConclusionThis study demonstrates that high level of sHLA-G in the genital mucosa is independently associated with both HIV-1 infection and bacterial vaginosis.
| S-EPMC3179477 | biostudies-literature
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.
| S-EPMC4320978 | biostudies-literature
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.
| S-EPMC6538542 | biostudies-other
Project description:CD161 identifies a subset of circulating Th17 cells that are depleted in the blood and gut of HIV-infected individuals. In the female reproductive tract (FRT), the pattern of CD161 expression on CD4+ cells remains unknown. Here, we characterized CD161 expression in the FRT of Kenyan female sex workers (FSW). Compared to the blood, CD161+CD4+ T cells were enriched in the FRT of uninfected FSWs. These cells were depleted in FRT of HIV-infected FSWs. Cervical CD161+ cells harboured an activated phenotype (CD69, CD95, HLA-DR) with elevated expression of tissue-homing markers (CCR6, β7 integrin) and HIV co-receptor (CCR5). Mitogen-stimulated production of IL-17 confirmed the Th17 commitment of CD161+CD4+ T cells in the FRT with a predominance of polyfunctional Th1/Th17 cells. Here, we showed that the expression of CD161 on CD4+T cells is modulated at the FRT, but still identified a highly activated cellular subset, which differentiates into pro-inflammatory Th1/Th17 cells, expresses multiple HIV susceptibility markers and are depleted in HIV-infected individuals. The use of CD161 as a biomarker of HIV targets in the FRT reduces the need for functional assessment of cells and could have important implications in better understanding HIV pathogenesis and Th17 fate in the FRT of high-risk women.
| S-EPMC5593931 | biostudies-literature
Project description:BackgroundThe precise immune responses mediated by HLA class I molecules such as HLA-B*27:05 and HLA-B*57:01 that protect against HIV disease progression remain unclear. We studied a CRF01_AE clade HIV infected donor-recipient transmission pair in which the recipient expressed both HLA-B*27:05 and HLA-B*57:01.ResultsWithin 4.5 years of diagnosis, the recipient had progressed to meet criteria for antiretroviral therapy initiation. We employed ultra-deep sequencing of the full-length virus genome in both donor and recipient as an unbiased approach by which to identify specific viral mutations selected in association with progression. Using a heat map method to highlight differences in the viral sequences between donor and recipient, we demonstrated that the majority of the recipient's mutations outside of Env were within epitopes restricted by HLA-B*27:05 and HLA-B*57:01, including the well-studied Gag epitopes. The donor, who also expressed HLA alleles associated with disease protection, HLA-A*32:01/B*13:02/B*14:01, showed selection of mutations in parallel with disease progression within epitopes restricted by these protective alleles.ConclusionsThese studies of full-length viral sequences in a transmission pair, both of whom expressed protective HLA alleles but nevertheless failed to control viremia, are consistent with previous reports pointing to the critical role of Gag-specific CD8+ T cell responses restricted by protective HLA molecules in maintaining immune control of HIV infection. The transmission of subtype CRF01_AE clade infection may have contributed to accelerated disease progression in this pair as a result of clade-specific sequence differences in immunodominant epitopes.
| S-EPMC4487201 | biostudies-literature
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.
| S-EPMC7028952 | biostudies-literature
Project description:HIV-1-specific cytotoxic T cells (CTLs) play an important role in the control of HIV-1 subtype B or C infection. However, the role of CTLs in HIV-1 subtype A/E infection still remains unclear. Here we investigated the association of HLA class I alleles with clinical outcomes in treatment-naive Vietnamese infected with subtype A/E virus. We found that HLA-C*12:02 was significantly associated with lower plasma viral loads (pVL) and higher CD4 counts and that the HLA-A*29:01-B*07:05-C*15:05 haplotype was significantly associated with higher pVL and lower CD4 counts than those for individuals without these respective genotypes. Nine Pol and three Nef mutations were associated with at least one HLA allele in the HLA-A*29:01-B*07:05-C*15:05 haplotype, with a strong negative correlation between the number of HLA-associated Pol mutations and CD4 count as well as a positive correlation with pVL for individuals with these HLA alleles. The results suggest that the accumulation of mutations selected by CTLs restricted by these HLA alleles affects HIV control.IMPORTANCE Most previous studies on HLA association with disease progression after HIV-1 infection have been performed on cohorts infected with HIV-1 subtypes B and C, whereas few such population-based studies have been reported for cohorts infected with the Asian subtype A/E virus. In this study, we analyzed the association of HLA class I alleles with clinical outcomes for 536 HIV-1 subtype A/E-infected Vietnamese individuals. We found that HLA-C*12:02 is protective, while the HLA haplotype HLA-A*29:01-B*07:05-C*15:05 is deleterious. The individuals with HIV-1 mutations associated with at least one of the HLA alleles in the deleterious HLA haplotype had higher plasma viral loads and lower CD4 counts than those of individuals without the mutations, suggesting that viral adaptation and escape from HLA-mediated immune control occurred. The present study identifies a protective allele and a deleterious haplotype for HIV-1 subtype A/E infection which are different from those identified for cohorts infected with HIV-1 subtypes B and C.
| S-EPMC5809730 | biostudies-literature