Natural control of HIV infection in young women in South Africa: HPTN 068.
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ABSTRACT:
SUBMITTER: Sivay MV
PROVIDER: S-EPMC6442735 | biostudies-literature | 2018 Oct
REPOSITORIES: biostudies-literature
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Project description:BackgroundSouth Africa has one of the highest rates of HIV-1 (HIV) infection world-wide, with the highest rates among young women. We analyzed the molecular epidemiology and evolutionary history of HIV in young women attending high school in rural South Africa.MethodsSamples were obtained from the HPTN 068 randomized controlled trial, which evaluated the effect of cash transfers for school attendance on HIV incidence in women aged 13-20 years (Mpumalanga province, 2011-2015). Plasma samples from HIV-infected participants were analyzed using the ViroSeq HIV-1 Genotyping assay. Phylogenetic analysis was performed using 200 pol gene study sequences and 2,294 subtype C reference sequences from South Africa. Transmission clusters were identified using Cluster Picker and HIV-TRACE, and were characterized using demographic and other epidemiological data. Phylodynamic analyses were performed using the BEAST software.ResultsThe study enrolled 2,533 young women who were followed through their expected high school graduation date (main study); some participants had a post-study assessment (follow-up study). Two-hundred-twelve of 2,533 enrolled young women had HIV infection. HIV pol sequences were obtained for 94% (n = 201/212) of the HIV-infected participants. All but one of the sequences were HIV-1 subtype C; the non-C subtype sequence was excluded from further analysis. Median pairwise genetic distance between the subtype C sequences was 6.4% (IQR: 5.6-7.2). Overall, 26% of study sequences fell into 21 phylogenetic clusters with 2-6 women per cluster. Thirteen (62%) clusters included women who were HIV-infected at enrollment. Clustering was not associated with study arm, demographic or other epidemiological factors. The estimated date of origin of HIV subtype C in the study population was 1958 (95% highest posterior density [HPD]: 1931-1980), and the median estimated substitution rate among study pol sequences was 1.98x10-3 (95% HPD: 1.15x10-3-2.81x10-3) per site per year.ConclusionsPhylogenetic analysis suggests that multiple HIV subtype C sublineages circulate among school age girls in South Africa. There were no substantive differences in the molecular epidemiology of HIV between control and intervention arms in the HPTN 068 trial.
| S-EPMC6033411 | biostudies-literature
Project description:BackgroundAntiretroviral (ARV) drugs are used for HIV treatment and prevention. We analyzed ARV drug use and HIV drug resistance in a cohort of young women in rural South Africa enrolled in the HIV Prevention Trials Network (HPTN) 068 study, which evaluated the use of a cash transfer conditional on school attendance to reduce HIV incidence.MethodsARV drug testing was performed using plasma samples from 2526 young women. This included 2526 enrollment samples (80 HIV-infected and 2446 HIV-uninfected) and 162 seroconversion samples (first HIV-positive study visit). Testing was performed using a qualitative assay that detects 20 ARV drugs from 5 drug classes. HIV drug resistance testing was performed with the ViroSeq HIV-1 Genotyping System for samples that had HIV viral loads ≥400 copies per milliliter.ResultsAt enrollment, ARV drugs were detected in 10 (12.5%) of 80 HIV-infected young women. None of 2446 HIV-uninfected young women had ARV drugs detected at enrollment. ARV drugs were also detected in 16 (9.9%) of 162 seroconverters. At enrollment, 9 (13.4%) of 67 young women with genotyping results had HIV drug resistance; resistance was also detected in 9 (6.9%) of 131 seroconverters with genotyping results.ConclusionsMost of the HIV-infected young women in this cohort from rural South Africa were not taking ARV drugs, suggesting they were unaware of their HIV status or were not in care. HIV drug resistance was detected in young women with both prevalent and new HIV infection.
| S-EPMC6185777 | biostudies-literature
Project description:Executive function (EF) may predict sexual risk-taking and HIV risk in young women in rural South Africa. We tested associations between EF and seven risky behavioural outcomes: binge drinking, illicit substance use, unprotected vaginal sex, concurrent sexual relationships, transactional sex, herpes simplex virus type 2 (HSV-2) infection, and HIV infection. We compared EF in young women with HIV to matched controls. 1080 young women underwent cognitive assessments. Better verbal short-term memory was associated with a lower risk of HSV-2 (OR 0.77; 95% CI 0.69, 0.86; p < 0.001). Uncorrected trends (p < 0.05) were better verbal working memory being associated with a lower risk of concurrency, better planning with a lower risk of illicit drug use, and better affective inhibition with a lower risk of transactional sex. 78 participants with sexually acquired HIV were matched with 153 HIV-negative controls and had poorer verbal working memory than controls (Hedge's g = -0.38; 95% CI -0.66, -0.10; p = 0.0076), but this was non-significant after adjustment. EF's contribution to young women's risky behaviour in this context does not hold when stringent statistical corrections are applied, with only verbal short term memory reaching statistical significance as predictor. Replication in other samples is recommended.
| S-EPMC8650142 | biostudies-literature
Project description:Sexual liaisons between older men and younger women have been linked to greater risk of HIV acquisition. This study aims to (1) identify psychosocial and behavioral factors associated with age-discordant (partner ?5 years) versus age-concordant partnerships (-1< partner <5) and (2) examine the association between partner age discordance and young South African women's sexual behavior.We used generalized estimating equations to analyze responses from 656 sexually experienced women (aged 13-20 years) from rural Mpumalanga province.Partner age discordance was associated with greater odds of reporting both more frequent sex [adjusted odd ratio (aOR) = 1.77; 95% confidence interval (CI): 1.20 to 2.60] and having a partner with concurrent partnerships (aOR = 1.77; 95% CI: 1.22 to 2.57). Age-discordant partnerships were associated with greater odds of casual partnerships (aOR = 1.50; 95% CI: 1.06 to 2.13), having a partner with concurrent partnerships (aOR = 1.71; 95% CI: 1.19 to 2.46), and more frequent intercourse (ie, having sex at least 2 or 3 times per month) (aOR = 2.04; 95% CI: 1.39 to 3.00). They were associated with lower odds of reporting condom use at last sex (aOR = 0.70; 95% CI: 0.50 to 0.98) and always using condoms (aOR = 0.53; 95% CI: 0.32 to 0.88) in age-discordant partnerships.Our findings suggest that a history of age-discordant partnerships, and to a lesser extent having an age-discordant partner, is linked to HIV risk among young South African women; however, the link between partner age discordance and HIV risk may be more strongly related to the characteristics of age-discordant partnerships than to the characteristics of young women who form such partnerships.
| S-EPMC4925181 | biostudies-literature
Project description:ABSTRACTStressful life circumstances (e.g. violence and poverty) have been associated with elevated biomarkers, including C-reactive protein (CRP), cytomegalovirus (CMV), and herpes simplex virus type-1 (HSV-1), among older adults in high-income settings. Yet, it remains unknown whether these relationships exist among younger populations in resource-limited settings. We therefore utilised a cohort of 1,279 adolescent girls and young women (AGYW) from the HIV Prevention Trials Network 068 study in rural South Africa to examine the associations between 6 hypothesized stressors (intimate partner violence (IPV), food insecurity, depression, socioeconomic status (SES), HIV, childhood violence) and 3 biomarkers that were measured using dried blood spots (CRP, CMV, and HSV-1). Ordinal logistic regression estimated the lagged and cross-sectional associations between each stressor and each biomarker. IPV was cross-sectionally associated with elevated CMV (OR = 2.45, 95% CI = 1.05,5.72), while low SES was cross-sectionally associated with reduced CMV (OR = 0.73, 95% CI = 0.58,0.93). AGYW with HIV had elevated biomarkers cross-sectionally (CRP: OR = 1.51, 95% CI = 1.08,2.09; CMV: OR = 1.86, 95% CI = 1.31,2.63; HSV-1: OR = 1.68, 95% CI = 1.17,2.41) and in a lagged analysis. The association between violence and CMV could help explain how violence results in stress and subsequently worse health among AGYW; however, additional research is needed to disentangle the longitudinal nature of IPV and stress.
| S-EPMC10580295 | biostudies-literature
Project description:BackgroundNearly all population-level research showing positive associations between age-disparate partnerships and HIV acquisition among adolescent girls and young women (AGYW) has classified age disparity as ≥5 or ≥10 years. We describe variations in 1-year risk of HIV infection after exposure to sexual partner(s) of continuous age disparities.MethodsLongitudinal data from the HPTN 068 randomized trial in South Africa were used to estimate 1-year risk of HIV infection at various age pairings. The parametric g-formula was used to estimate risk at up to 5 annual time points, stratified by maximum partner age difference, maximum partner age, and AGYW age.ResultsAGYW reported an older partner in 86% of 5351 age pairings. The 1-year risk of HIV infection rapidly increased with maximum partner age difference among girls ages 13-14 years, from 0·01 with a same-age partner, to 0·21 with a partner 10 years older, and 0·24 with a partner 15 years older. A gradual increase occurred among AGYW ages 15-16 years, up to 0·13 with a partner 15 years older, and 0·09 among AGYW 17-18 years with partners 8-11 years older. Risk of HIV infection among AGYW ages 19-21 years remained relatively constant across maximum partner age differences.ConclusionsAge differences between AGYW and their sexual partners have a greater effect on HIV-risk infection in younger compared with older AGYW. Considering both the age of an AGYW and her sexual partners provides granular insight into identifying key groups for HIV transmission prevention efforts.
| S-EPMC7722780 | biostudies-literature
Project description:Background. Prevention of both school dropout and teen pregnancy represent clear public health priorities for South Africa, yet their complex and potentially cyclical relationship has not been fully explored. Objective. To further understand how this relationship operates, we analyzed data from a randomized trial of young women aged 13 to 20 years enrolled in school in rural South Africa to estimate the association between pregnancy and subsequent dropout and between dropout and subsequent pregnancy. Method. We examined inverse probability (IP) of exposure-weighted survival curves for school dropout by pregnancy and for pregnancy by school dropout. We used weighted curves to calculate 1-, 2-, and 3-year risk differences and risk ratios. Additionally, we used an IP-weighted marginal structural cox model to estimate a hazard ratio (HR) for each relationship. Results. Dropout from school was associated with subsequent pregnancy (HR 3.58; 95% confidence interval [CI] [2.04, 6.28]) and pregnancy was associated with subsequent school dropout (HR 2.36; 95% CI [1.29, 4.31]). Young women who attended school but attended fewer days had a higher hazard of pregnancy than those who attended more school (HR 3.64; 95% CI [2.27, 5.84]). Conclusion. Pregnancy is both a cause and a consequence of school dropout. Consideration of school attendance and academic performance could ultimately enhance pregnancy prevention efforts in this population. Programs should be tailored differently for (1) girls who have dropped out of school, (2) those who are in school and at risk for pregnancy, and (3) those who are in school and become pregnant.
| S-EPMC6625926 | biostudies-literature
Project description:BackgroundCash transfers have been proposed as an intervention to reduce HIV-infection risk for young women in sub-Saharan Africa. However, scarce evidence is available about their effect on reducing HIV acquisition. We aimed to assess the effect of a conditional cash transfer on HIV incidence among young women in rural South Africa.MethodsWe did a phase 3, randomised controlled trial (HPTN 068) in the rural Bushbuckridge subdistrict in Mpumalanga province, South Africa. We included girls aged 13-20 years if they were enrolled in school grades 8-11, not married or pregnant, able to read, they and their parent or guardian both had the necessary documentation necessary to open a bank account, and were residing in the study area and intending to remain until trial completion. Young women (and their parents or guardians) were randomly assigned (1:1), by use of numbered sealed envelopes containing a randomisation assignment card which were numerically ordered with block randomisation, to receive a monthly cash transfer conditional on school attendance (≥80% of school days per month) versus no cash transfer. Participants completed an Audio Computer-Assisted Self-Interview (ACASI), before test HIV counselling, HIV and herpes simplex virus (HSV)-2 testing, and post-test counselling at baseline, then at annual follow-up visits at 12, 24, and 36 months. Parents or guardians completed a Computer-Assisted Personal Interview at baseline and each follow-up visit. A stratified proportional hazards model was used in an intention-to-treat analysis of the primary outcome, HIV incidence, to compare the intervention and control groups. This study is registered at ClinicalTrials.gov (NCT01233531).FindingsBetween March 5, 2011, and Dec 17, 2012, we recruited 10 134 young women and enrolled 2537 and their parents or guardians to receive a cash transfer programme (n=1225) or not (control group; n=1223). At baseline, the median age of girls was 15 years (IQR 14-17) and 672 (27%) had reported to have ever had sex. 107 incident HIV infections were recorded during the study: 59 cases in 3048 person-years in the intervention group and 48 cases in 2830 person-years in the control group. HIV incidence was not significantly different between those who received a cash transfer (1·94% per person-years) and those who did not (1·70% per person-years; hazard ratio 1·17, 95% CI 0·80-1·72, p=0·42).InterpretationCash transfers conditional on school attendance did not reduce HIV incidence in young women. School attendance significantly reduced risk of HIV acquisition, irrespective of study group. Keeping girls in school is important to reduce their HIV-infection risk.FundingNational Institute of Allergy and Infectious Diseases, National Institute of Mental Health of the National Institutes of Health.
| S-EPMC5626439 | biostudies-literature
Project description:Friends could be influential on young women's sexual health via influences on sexual behaviours and as connections to sexual partners, but are understudied in sub-Saharan Africa. We cross-sectionally surveyed 2326 13-20 year-old young women eligible for grades 8-11 in rural South Africa about their sexual behaviour and up to three sexual partners. Participants each described five specific but unidentified friends and the relationships between them in an 'egocentric' network analysis design. We used logistic regression to investigate associations between friendship characteristics and participants' reports of ever having had sex (n?=?2326) and recent condom use (n?=?457). We used linear regression with random effects by participant to investigate friendship characteristics and age differences with sexual partners (n?=?633 participants, 1051 partners). We found that it was common for friends to introduce young women to those who later became sexual partners, and having older friends was associated with having older sexual partners, (increase of 0.37 years per friend at least 1 year older, 95% CI 0.21-0.52, adjusted). Young women were more likely to report ever having had sex when more friends were perceived to be sexually active (adjusted OR 1.85, 95% CI 1.72-2.01 per friend) and when they discussed sex, condoms and HIV with friends. Perception of friends' condom use was not associated with participants' reported condom use. While this study is preliminary and unique in this population and further research should be conducted, social connections between friends and sexual partners and perceptions of friend sexual behaviours could be considered in the design of sexual health interventions for young women in South Africa.
| S-EPMC6703905 | biostudies-literature
Project description:BackgroundSexual partners are the primary source of incident HIV infection among adolescent girls and young women (AGYW) in sub-Saharan Africa. Identifying partner types at greatest risk of HIV transmission could guide the design of tailored HIV prevention interventions.MethodsWe conducted a secondary analysis of data from AGYW (aged 13-23 years) enrolled in a randomized controlled trial of cash transfers for HIV prevention in South Africa. Annually, AGYW reported behavioral and demographic characteristics of their 3 most recent sexual partners, categorized each partner using prespecified labels, and received HIV testing. We used latent class analysis (LCA) to identify partner types from reported characteristics, and generalized estimating equations to estimate the relationship between both LCA-identified and prespecified partner types and incident HIV infection.ResultsAcross 2140 AGYW visits, 1034 AGYW made 2968 partner reports and 63 AGYW acquired HIV infection. We identified 5 LCA partner types, which we named monogamous HIV-negative peer partner; one-time protected in-school peer partner; out-of-school older partner; anonymous out-of-school peer partner; and cohabiting with children in-school peer partner. Compared to AGYW with only monogamous HIV-negative peer partners, AGYW with out-of-school older partners had 2.56 times the annual risk of HIV infection (95% confidence interval: 1.23 to 5.33), whereas AGYW with anonymous out-of-school peer partners had 1.72 times the risk (95% confidence interval: 0.82 to 3.59). Prespecified partner types were not associated with incident HIV.ConclusionBy identifying meaningful combinations of partner characteristics and predicting the corresponding risk of HIV acquisition among AGYW, LCA-identified partner types may provide new insights for the design of tailored HIV prevention interventions.
| S-EPMC6692200 | biostudies-literature