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South Africa is faced with a high HIV and STI prevalence and incidence, respectively, with pockets of high burden areas driving these diseases. Localised monitoring of the HIV epidemic and STI endemic would enable more effective targeted prevention strategies. We assessed spatial variations in curable STI incidence among a cohort of women enrolled in HIV prevention clinical trials between 2002 and 2012. STI incidence rates from 7557 South African women enrolled in five HIV prevention trials were geo-mapped using participant household GPS coordinates. Age and period standardised incidence rates were calculated for 43 recruitment areas and Bayesian conditional autoregressive areal spatial regression (CAR) was used to identify significant patterns and spatial patterns of STI infections in recruitment communities. Overall age and period standardised STI incidence rate were estimated as 15 per 100 PY and ranged from 6 to 24 per 100 PY. We identified five significant STI high risk areas with higher-than-expected incidence of STIs located centrally (three-locations) and southern neighbouring areas of Durban (two-locations). Younger age (<25), not married/cohabitating, parity <3 and poor education were all significant correlates of high STI communities. Findings demonstrate sustained STI incidence rates across the greater Durban area. The role of STI incidence in HIV acquisition in high HIV endemic areas need to be revisited as current highly effective PrEP interventions do not protect from STI acquisition. In these settings there is an urgent need for integrative HIV and STI prevention and treatment services.

Objective: Development of immunogens that elicit an anti-HIV-1 broadly neutralizing antibody (bnAb) response will be a key step in the development of an effective HIV-1 vaccine. Although HIV-1 bnAb epitopes have been identified and mechanisms of action studied, current HIV-1 envelope-based immunogens do not elicit HIV-1 bnAbs in humans or animal models. A better understanding of how HIV-1 bnAbs arise during infection and the clinical factors associated with bnAb development may be critical for HIV-1 immunogen design efforts., Design and Methods: Longitudinal plasma samples from the treatment-naive control arm of the Short Pulse Anti-Retroviral Therapy at Seroconversion (SPARTAC) primary HIV-1 infection cohort were used in an HIV-1 pseudotype neutralization assay to measure the neutralization breadth, potency and specificity of bnAb responses over time., Results: In the SPARTAC cohort, development of plasma neutralization breadth and potency correlates with duration of HIV infection and high viral loads, and typically takes 3-4 years to arise. bnAb activity was mostly directed to one or two bnAb epitopes per donor and more than 60% of donors with the highest plasma neutralization having bnAbs targeted towards glycan-dependent epitopes., Conclusion: This study highlights the SPARTAC cohort as an important resource for more in-depth analysis of bnAb developmental pathways., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc.)

Curable sexually transmitted infections (STIs) affect millions of people across the world. Besides unacceptably high HIV rates, South Africa also has the highest burden of STIs in the world. The aim of the study was to investigate temporal changes in STI incidence rates using the data from ~ 10,000 women who enrolled in several HIV prevention trials, KwaZulu-Natal, South Africa (2002-2016). We particularly focused on the changes in distribution of the most influential factors and their population-level impacts on STI incidence rates over time. Characteristics of the women were compared across the study periods: 2002-2004, 2005-2008, 2009-2011, and 2012-2016. Besides multivariable Cox regression models, population attributable risks were calculated for the significant factors. Despite the significant progress in prevention, testing, and treatment programs, infection rates increased substantially from 13.6 to 20.0 per 100 person-year over the study period. Our findings provided a compelling evidence for single/non-cohabiting South African women to be the most vulnerable population who consistently and substantially contributed to increasing STI rates during the 15 years of study duration (PAR%: 44%-47%). We also highlighted the impact of women's lack of knowledge related to their partner, using injectable contraceptives, less parity, and baseline STI positivity which were increased substantially over time. Our findings suggest that a significant proportion of STIs could be prevented by targeting single/non-cohabiting. These results may provide guidance in developing more effective STI prevention programs by targeting women at highest risk of infections and delivering more realistic messages., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

South Africa has the highest number of HIV infected individuals in the world. The primary objective of the current study was to describe temporal changes in HIV incidence rates using the data from 9,948 women who enrolled in one of the six HIV prevention trials conducted in KwaZulu-Natal, South Africa. Characteristics of the study population were presented and compared across the four study periods: 2002-2004, 2005-2008, 2009-2011 and 2012-2016. HIV infection rates increased from 6.2 to 9.3 per 100 person-year over the 15 years. These rates were as high as 14 per 100 person-year among women younger than 20 years age. Being single/not cohabiting, using injectable contraceptives, having less than two children, and diagnosed with STI(s) were associated with increased risk of HIV infection. These four factors were associated with 71%, 75%, 80% and 88% of the HIV seroconversions in four study periods. As the research continues to find ways of controlling the spread of the infections, quantifying the temporal trends in risk factors and their population-level impacts on HIV infection may have significant implications. This information may assist in developing effective counselling and education programs by targeting the sexually active single women and delivering more realistic messages.

In this study, we investigated spatial diversities of sexually transmitted infections (STIs) and quantified their impacts on the STIs using population attributable risk (PAR%). The study population was 7,557 women who participated in several HIV prevention trials from KwaZulu-Natal, South Africa. Our results provide compelling evidence for substantial geographical diversities on STI incidence rates in the region. Their population-level impacts on the STIs exceeded the combined impacts of the individual risk factors considered in this study (PAR%: 41% (<25 years), 52% (25-34 years) and 34% (35+ years). When all these factors are considered together, PAR% was the highest among younger women (PAR%: 67%, 82% and 50% for <25, 25-34 and 35+ years old respectively). Results from our study will bring greater insight into the previous research by increasing our understanding of the impacts of the sub-geographical level variations of STI prevalence and incidence rates in the region.

Despite expanded antiretroviral therapy (ART) eligibility in South Africa, many people diagnosed with HIV do not initiate ART promptly, yet understanding of the reasons is limited. Using data from an 8-month prospective cohort interview study of women and men newly-diagnosed with HIV in three public-sector primary care clinics in the eThekwini (Durban) region, South Africa, 2010-2014, we examined if theoretically-relevant social-structural, social-cognitive, psychosocial, and health status indicators were associated with time to ART initiation. Of 459 diagnosed, 350 returned to the clinic for their CD4+ test results (linkage); 153 (33.3%) were ART-eligible according to treatment criteria at the time; 115 (75.2% of those eligible) initiated ART (median = 12.86 weeks [95% CI: 9.75, 15.97] after linkage). In adjusted Cox proportional hazard models, internalized stigma was associated with a 65% decrease in the rate of ART initiation (Adjusted hazard ratio [AHR] 0.35, 95% CI: 0.19-0.80) during the period less than four weeks after linkage to care, but not four or more weeks after linkage to care, suggesting that stigma-reduction interventions implemented shortly after diagnosis may accelerate ART uptake. As reported by others, older age was associated with more rapid ART initiation (AHR for 1-year age increase: 1.04, 95% CI: 1.01-1.07) and higher CD4+ cell count (≥300μL vs. <150μL) was associated with a lower rate of initiation (AHR 0.38, 95% CI: 0.19-0.80). Several other factors that were assessed prior to diagnosis, including stronger belief in traditional medicine, higher endorsement of stigma toward people living with HIV, food insecurity, and higher psychological distress, were found to be in the expected direction of association with ART initiation, but confidence intervals were wide and could not exclude a null finding., Competing Interests: The authors have declared that no competing interests exist.

Background: Two phase 3 clinical trials showed that use of a monthly vaginal ring containing 25 mg dapivirine was well tolerated and reduced HIV-1 incidence in women by approximately 30% compared with placebo. We aimed to evaluate use and safety of the dapivirine vaginal ring (DVR) in open-label settings with high background rates of HIV-1 infection, an important step for future implementation., Methods: We did a phase 3B open-label extension trial of the DVR (MTN-025/HIV Open-label Prevention Extension [HOPE]). Women who were HIV-1-negative and had participated in the MTN-020/ASPIRE phase 3 trial were offered 12 months of access to the DVR at 14 clinical research centres in Malawi, South Africa, Uganda, and Zimbabwe. At each visit (monthly for 3 months, then once every 3 months), women chose whether or not to accept the offer of the ring. Used, returned rings were tested for residual amounts of dapivirine as a surrogate marker for adherence. HIV-1 serological testing was done at each visit. Dapivirine amounts in returned rings and HIV-1 incidence were compared with data from the ASPIRE trial, and safety was assessed. This study is registered with ClinicalTrials.gov, NCT02858037., Findings: Between July 16, 2016, and Oct 10, 2018, of 1756 women assessed for eligibility, 1456 were enrolled and participated in the study. Median age was 31 years (IQR 27-37). At baseline, 1342 (92·2%) women chose to take the DVR; ring acceptance was more than 79% at each visit up until 12 months and 936 (73·2%) of 1279 chose to take the ring at all visits. 12 530 (89·3%) of 14 034 returned rings had residual dapivirine amounts consistent with some use during the previous month (>0·9 mg released) and the mean dapivirine amount released was greater than in the ASPIRE trial (by 0·21 mg; p<0·0001). HIV-1 incidence was 2·7 per 100 person-years (95% CI 1·9-3·8, 35 infections), compared with an expected incidence of 4·4 per 100 person-years (3·2-5·8) among a population matched on age, site, and presence of a sexually transmitted infection from the placebo group of ASPIRE. No serious adverse events or grade 3 or higher adverse events observed were assessed as related to the DVR., Interpretation: High uptake and persistent use in this open-label extension study support the DVR as an HIV-1 prevention option for women. With an increasing number of HIV-1 prophylaxis choices on the horizon, these results suggest that the DVR will be an acceptable and practical option for women in Africa., Funding: The Microbicide Trials Network and the National Institute of Allergy and Infectious Diseases, The Eunice Kennedy Shriver National Institute of Child Health and Human Development, and the National Institute of Mental Health, all components of the US National Institutes of Health., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: The Pox-Protein Public-Private Partnership is performing a suite of trials to evaluate the bivalent subtype C envelope protein (TV1.C and 1086.C glycoprotein 120) vaccine in the context of different adjuvants and priming agents for human immunodeficiency virus (HIV) type 1 (HIV-1) prevention., Methods: In the HIV Vaccine Trials Network 111 trial, we compared the safety and immunogenicity of DNA prime followed by DNA/protein boost with DNA/protein coadministration injected intramuscularly via either needle/syringe or a needle-free injection device (Biojector). One hundred thirty-two healthy, HIV-1-uninfected adults were enrolled from Zambia, South Africa, and Tanzania and were randomized to 1 of 6 arms: DNA prime, protein boost by needle/syringe; DNA and protein coadministration by needle/syringe; placebo by needle/syringe; DNA prime, protein boost with DNA given by Biojector; DNA and protein coadministration with DNA given by Biojector; and placebo by Biojector., Results: All vaccinations were safe and well tolerated. DNA and protein coadministration was associated with increased HIV-1 V1/V2 antibody response rate, a known correlate of decreased HIV-1 infection risk. DNA administration by Biojector elicited significantly higher CD4+ T-cell response rates to HIV envelope protein than administration by needle/syringe in the prime/boost regimen (85.7% vs 55.6%; P = .02), but not in the coadministration regimen (43.3% vs 48.3%; P = .61)., Conclusions: Both the prime/boost and coadministration regimens are safe and may be promising for advancement into efficacy trials depending on whether cellular or humoral responses are desired., Clinical Trials Registration: South African National Clinical Trials Registry (application 3947; Department of Health [DoH] no. DOH-27-0715-4917) and ClinicalTrials.gov (NCT02997969)., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America.)

Low adherence in vaginal microbicide clinical trials for HIV prevention has impeded interpretation of trial results and hindered evaluation of potentially efficacious HIV prevention gels. Understanding the underlying reasons why women join trials and their barriers to product use can support identification of ways to improve adherence and its reporting. Eight focus group discussion workshops were conducted with 46 former microbicide trial participants in Durban, South Africa and Mwanza, Tanzania. Participants provided feedback on why women join trials, the barriers to using study gel and reporting adherence accurately, and how clinical trial design can be improved to support better adherence and its reporting. Women join microbicide trials for a number of important reasons such as healthcare and financial reimbursement. Fear of adverse effects from the investigational product was the most important reason why participants reported not using the gel. The key reason for inaccurate reporting of gel use was fear of removal from the trial. Participants made concrete suggestions for improving microbicide trial design such as applicator use testing and real time feedback, improving education to participants about how trials answer their research questions, and improving transparency and clarity about study procedures. Participants also gave feedback on an innovative trial design with a non-randomised arm. Identifying HIV prevention products for women requires better understanding of the lives of women asked to join these trials, and application of that understanding to microbicide trial design. This study has demonstrated that participants and research teams can work collaboratively to design clinical trials that meet needs of both the research and of participants., Competing Interests: The authors have declared that no competing interests exist.

Background: Low adherence has contributed to disappointing results for trials testing vaginal microbicides for HIV prevention. This study engaged former gel trial participants to understand the reasons behind low adherence and seek suggestions on how to improve products and adherence to microbicides. This analysis examines the impact of participant perceptions of male partners on participant adherence and suggestions on how to address those issues., Methods: Eight focus group discussion workshops were conducted with 46 former microbicide trial participants in South Africa and Tanzania. Participants provided feedback on why women join trials, barriers to using gels and reporting adherence accurately, and how adherence and adherence reporting can be improved., Results: Participants reported that male partners can affect women's ability to use gels. For some, the lubricating effects caused relationship conflicts due to suspicion of male partners about infidelity. Needing to provide sex to partners on demand was a barrier to gel use. Participants suggested a gel formulation which was thicker and less noticeable, and explicit male partner engagement to enhance understanding of the purpose of the gels., Conclusions: The imbalance of power in intimate relationships affects the ability of women to use microbicides as directed. To improve adherence to HIV prevention methods within trials and for successful rollout of proven HIV prevention methods in populations, it is important that the complicated dynamics of sex and relationships be taken into greater consideration and that women receive targeted support to navigate product use and communication within the context of these gender dynamics.

Objective: Despite all efforts, high pregnancy rates are often reported in HIV biomedical intervention trials conducted in African countries. We therefore aimed to develop a pregnancy risk scoring algorithm for targeted recruitment and screening strategies among a cohort of women in South Africa., Methods: The study population was ~ 10,000 women who enrolled in one of the six biomedical intervention trials conducted in KwaZulu Natal, South Africa. Cox regression models were used to create a pregnancy risk scoring algorithm which was internally validated using standard statistical measures., Results: Five factors were identified as significant predictors of pregnancy incidence:<25 years old, not using injectable contraceptives, parity (<3), being single/not cohabiting and having ≥ 2 sexual partners in the past three months. Women with total scores of 21-24, 25-35 and 36+ were classified as being at "moderate", "high", "severe" risk of pregnancy. Sensitivity of the development and validation models were reasonably high (sensitivity 76% and 74% respectively)., Conclusion: Our risk scoring algorithm can identify and alert researchers to women who need additional non-routine pregnancy assessment and counselling, with statistically acceptable accuracy and robustness., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Introduction: Some observational data suggest that the progestogen injectable contraceptive depot medroxyprogesterone acetate (DMPA) may increase a woman's risk of HIV acquisition but a randomized clinical trial did not find a statistically significant increase in HIV risk for women using DMPA compared to two other methods. However, it could not rule out up to 30% increased HIV risk for DMPA users. We evaluate changes to contraceptive method mix in South Africa under different assumptions about the existence and strength of a possible undetected relationship between DMPA use and HIV risk., Methods: A mathematical model was developed to simulate the ongoing HIV epidemic and contraceptive method mix in South Africa to estimate how changes in method mix could impact HIV- and reproductive health-related outcomes. We made different assumptions about the relationship between DMPA use and HIV risk, from no relationship to a 30% increase in HIV risk for women using DMPA. Scenario analyses were used to investigate the impact of switching away from DMPA predominance to new patterns of contraceptive use., Results: In South Africa, the HIV-related benefits of reduced DMPA use could be as great as the harms of increased adverse reproductive health outcomes over 20 years, if DMPA did increase the risk of HIV acquisition by a relative hazard of infection of 1.1 or greater. A reduction in DMPA use among HIV-positive women would have no benefit in terms of HIV infections, but would incur additional negative reproductive health outcomes. The most important driver of adverse reproductive health outcomes is the proportion of women who switch away from DMPA to no contraceptive method., Conclusions: If there is any real increased HIV risk for DMPA users that has not been detected by the recent randomized trial, a reduction in DMPA use could reduce the ongoing number of new HIV infections. However, such a change would place more women at risk of adverse reproductive health effects. It is imperative that these effects are minimized by focusing on expanding access to safe, effective and acceptable alternative contraceptive methods for all women., (© 2020 The Authors. Journal of the International AIDS Society published by John Wiley & Sons Ltd on behalf of the International AIDS Society.)

Linkage to care following an HIV diagnosis remains an important HIV care continuum milestone, even in the era of universal ART eligibility. In an 8-month prospective cohort study among 459 (309 women, 150 men) newly-diagnosed HIV-positive individuals in three public-sector clinics in Durban metropolitan region, South Africa, from 2010 to 2013, median time to return to clinic for CD4+ results (linkage) was 10.71 weeks (95% CI 8.52-12.91), with 54.1% 3-month cumulative incidence of linkage. At study completion (9.23 months median follow-up), 26.2% had not linked. Holding more positive outcome-beliefs about enrolling in care was associated with more rapid linkage [adjusted hazard ratio (AHR) each additional belief 1.31; 95% CI 1.05-1.64] and lower odds of never linking [adjusted odds ratio (AOR) 0.50; 95% CI 0.33-0.75]. Holding positive ARV beliefs was strongly protective against never linking to care. Age over 30 years (AHR 1.59; 95% CI 1.29-1.97) and disclosing one's HIV-positive status within 30 days of diagnosis (AHR 1.52; 95% CI 1.10-2.10) were associated with higher linkage rates and lower odds of never linking. Gender was not associated with linkage and did not alter the effect of other predictors. Although expanded access to ART has reduced some linkage barriers, these findings demonstrate that people's beliefs and social relations also matter. In addition to structural interventions, consistent ART education and disclosure support, and targeting younger individuals for linkage are high priorities.

Background: WHO guidelines recommend co-trimoxazole prophylaxis for HIV-exposed, HIV-uninfected infants. These guidelines date back to an era in which HIV testing of infants was impossible and mothers had poor access to antiretroviral treatment. To determine whether this guideline requires revision in the current era of effective prevention of mother-to-child transmission and early infant diagnosis programmes, we aimed to investigate whether receiving no co-trimoxazole prophylaxis is inferior to receiving co-trimoxazole prophylaxis in the resulting incidence of grade 3 or 4 common childhood illnesses or mortality in breastfed HIV-exposed, HIV-uninfected infants., Methods: We investigated our aim in a randomised controlled, non-inferiority trial. We enrolled the HIV-negative infants of mothers living with HIV who were actively involved in transmission prevention programmes in two clinics in Durban, South Africa. Infants were included in the study if they were breastfeeding at the screening and enrolment visits, and their mother was planning to breastfeed for at least 6 months; were a singleton birth and had a birthweight of 2 kg or more; had no clinically observed genetic disorders; and had no serious illnesses and had not received antibiotics or traditional medications (such as herbal remedies). Infants were randomly assigned (1:1) to receive co-trimoxazole or no co-trimoxazole. In the co-trimoxazole group, infants received the drug until all exposure to HIV had ceased (ie, 6 weeks after last exposure to breastmilk) and the infant was confirmed to be uninfected with HIV. The drug was administered by mothers in once-daily regimens of 20 mg trimethoprim and 100 mg sulfamethoxazole orally (age <6 months or bodyweight <5 kg), or 40 mg trimethoprim and 200 mg sulfamethoxazole orally (age >6 months or bodyweight >5 kg). Clinical and laboratory staff always remained masked to group assignment, but mothers and study counsellors were not. Infants and their mothers attended study visits at ages 6 weeks (for enrolment and randomisation), 10 weeks, 14 weeks, and then monthly from 4 to 12 months. Our primary outcome was the incidence of grade 3 or 4 common childhood illnesses (pneumonia or diarrhoea) or mortality in breastfed HIV-exposed, HIV-uninfected infants by age 12 months. A non-inferiority bound of 5% was used. The study is registered with the Pan African Clinical Trials Registry, number PACTR201311000621110, and the South African National Clinical Trials Registry, number DOH-27-0614-4728., Findings: We screened 1570 mother-child pairs for study enrolment, from whom (78%) eligible infants were enrolled into the study between Oct 16, 2013, and May 23, 2018. Of the infants enrolled, 611 (50%) were randomly assigned to the co-trimoxazole group and 609 (50%) were randomly assigned to the no co-trimoxazole group. One (<1%) infant in the no co-trimoxazole group was excluded from the analysis of the final outcomes for having received traditional medicine (which only became apparent after randomisation); therefore, 611 (50%) infants in the co-trimoxazole group and 608 (50%) infants in the no co-trimoxazole group were included in the final intention-to-treat analysis. 136 (22%) infants in the co-trimoxazole group and 139 (23%) infants in the no co-trimoxazole group did not complete the 12-month study visit, predominantly because of loss to follow-up (93 [15%] infants in the co-trimoxazole group; 90 [15%] infants in the no co-trimoxazole group). The cumulative probability of the composite primary outcome was 0·114 (95% CI 0·076 to 0·147; 49 events) in the co-trimoxazole group versus 0·0795 (0·044 to 0·115; 39 events) in the no co-trimoxazole group. The risk difference (no co-trimoxazole group minus co-trimoxazole group) was -0·0319 (-0·075 to 0·011), meaning that the risk was around 3 percentage points lower in the no co-trimoxazole group on the additive scale., Interpretation: We can conclude that no co-trimoxazole is not inferior to daily co-trimoxazole among breastfed HIV-exposed, HIV-uninfected infants whose mothers are accessing a prevention of mother-to-child transmission programme in an area unaffected by malaria. We therefore believe that WHO should revise the co-trimoxazole guidelines for HIV-exposed, HIV-uninfected infants in areas unaffected by malaria., Funding: HIV Prevention Research Unit of the South African Medical Research Council and the Family Larsson-Rosenquist Foundation., (Copyright © 2019 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Objective: The aim of this proof of concept study was to determine the effect of depot medroxyprogesterone acetate on host and viral factors in HIV infected and uninfected women., Results: In this study, the gene expression levels for CCL5, CCR5 and CXCR4 was significantly higher in HIV positive women when compared to HIV negative women (p < 0.05). An upregulation of CCR5 and CXCR4 was evident in less than 20% of the HIV infected women and none of the HIV uninfected women. The mean fold change for CCL3 was much higher in HIV uninfected when compared to infected women with a borderline significance (p = 0.062). In HIV uninfected women, the mean fold change in CCL3, CCL4, and CCL5 gene expression was not statistically different between women on DMPA versus women not on hormonal contraception. The proportion of women with an upregulation of CCL4 and CCR5 was higher in HIV infected women on DMPA. There was no association between endogenous progesterone level and chemokines and the HIV-1 receptors. The gene expression levels in the chemokine receptors CCR5 and CXCR4 were significantly higher in the HIV infected women when compared to the women who remained HIV uninfected.

Objective: We identified the geographical clustering of HIV as well as those at highest risk of infection using a decade long data (2002-2012) from KwaZulu-Natal, South Africa., Methods: A total of 5,776 women who enrolled in several HIV prevention trials were included in the study. Geo-coded individual-level data were linked to the community-level characteristics using the South African Census. High-risk women were identified using a risk scoring algorithm. Generalized additive models were used to identify the significant geographical clustering of high-risk women and HIV., Results: Overall, 60% of the women were classified as high risk of HIV. HIV infection rates were estimated as high as 10 to 15 per 100 person year. Areas with high rates of HIV infections were spatially clustered and overlapped particularly in the Northern part of Durban., Conclusion: Targeting multifactorial and complex nature of the epidemic is urgently needed to identify the "high transmission" areas., (Copyright © 2019. Published by Elsevier Ltd.)

Background: A vaginal ring containing dapivirine, a non-nucleoside human immunodeficiency virus (HIV)-1 reverse transcriptase inhibitor (NNRTI), was safe and effective in preventing HIV-1 infection in African women. We examined the impact of dapivirine ring use at the time of HIV-1 acquisition on subsequent HIV-1 disease progression and responses to NNRTI-containing antiretroviral therapy (ART)., Methods: HIV-1 disease progression and virologic failure following initiation of ART were assessed among women who acquired HIV-1 while participating in Microbicide Trials Network-020, a randomized, placebo-controlled trial of a monthly, dapivirine vaginal ring., Results: Among the 158 participants who acquired HIV-1 (65 dapivirine, 93 placebo), no differences between dapivirine and placebo participants were observed in CD4+ cell counts or plasma HIV-1 RNA over the first year after infection (prior to ART). During follow-up, 100/158 (63%) participants initiated NNRTI-containing ART (dapivirine: 39/65; placebo: 61/93); the median time to HIV-1 RNA <200 copies/ml was approximately 90 days for both dapivirine and placebo ring recipients (log-rank P = .40). Among the 81 participants with at least 6 months of post-ART follow-up, 19 (24%) experienced virologic failure (dapivirine: 6/32, 19%; placebo: 13/39, 27%; P = .42)., Conclusions: The acquisition of HIV-1 infection during dapivirine or placebo treatment in ASPIRE did not lead to differences in HIV-1 disease progression. After the initiation of NNRTI-containing ART, dapivirine and placebo participants had similar times to virologic suppression and risks of virologic failure. These results provide reassurance that NNRTI-based ART regimens are effective among women who acquired HIV-1 while receiving the dapivirine vaginal ring., Clinical Trials Registration: NCT016170096 and NCT00514098., (© The Author(s) 2018. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Background: With Universal Health Coverage and Integrated People-centred Health Care, streamlined health-systems and respectful care are necessary. South Africa has made great strides in prevention of mother-to-child transmission (PMTCT) but with the great burden of HIV, a minimum of birth and 10-week HIV-PCR testing are required for the estimated 360,000 HIV-exposed infants born annually which presents many challenges including delayed results and loss to follow-up. Point-of-care (POC) HIV testing of infants addresses these challenges well and facilitates initiation of HIV-infected infants rapidly after diagnosis for best clinical outcomes., Methods: Objectives were to determine accuracy, feasibility and acceptability of POC testing compared to standard-of-care (SOC) central-laboratory testing. HIV-exposed infants for birth PCR testing in hospital (n = 323) and follow-up at a primary health care clinic (n = 117) in Durban, South Africa were included. A baseline situational-analysis reviewed registers and phoned mothers of HIV-exposed infants prior to the intervention. An effectiveness-implementation study of the Alere™q HIV-1/2 Detect POC test (heel-prick specimen processed in 50 min) was compared with SOC with questionnaires to mothers and staff. Stata 14 was used for analysis., Results: At baseline 2% of birth HIV tests were missed; only 40% of mothers could be contacted; 17% did not receive birth test result; 19% did not have a 10-week test; 39% had not received the 10-week results. There were 5(1.5%) HIV-infected and 318(98.5%) HIV-negative infants detected in hospital with all clinic babies negative. All positive infants commenced ART before discharge. Ultimately POC and SOC had perfect concordance but for 10 SOC tests researchers actively tracked-down results or repeated tests. Turn around times for SOC tests were on average 8-days (IQR 6-10  days) and for POC testing was 0-days. The POC error-rate was 9,6% with all giving a result when repeated. The majority of mothers (92%) preferred POC testing with 7% having no preference. No staff preferred SOC testing with 79% preferring POC and 21% having no preference., Conclusions: Point-of-care HIV testing for EID is accurate, feasible and acceptable, with benefits of early ART for all positive infants at birth facilities. We recommend that it be considered best practice for EID., Trial Registration: ISRCTN38911104 registered 9 January 2018 - retrospectively registered.

Background: Fine scale geospatial analysis of HIV infection patterns can be used to facilitate geographically targeted interventions. Our objective was to use the geospatial technology to map age and time standardized HIV incidence rates over a period of 10 years to identify communities at high risk of HIV in the greater Durban area., Methods: HIV incidence rates from 7557 South African women enrolled in five community-based HIV prevention trials (2002-2012) were mapped using participant household global positioning system (GPS) coordinates. Age and period standardized HIV incidence rates were calculated for 43 recruitment clusters across greater Durban. Bayesian conditional autoregressive areal spatial regression (CAR) was used to identify significant patterns and clustering of new HIV infections in recruitment communities., Results: The total person-time in the cohort was 9093.93 years and 613 seroconversions were observed. The overall crude HIV incidence rate across all communities was 6·74 per 100PY (95% CI: 6·22-7·30). 95% of the clusters had HIV incidence rates greater than 3 per 100PY. The CAR analysis identified six communities with significantly high HIV incidence. Estimated relative risks for these clusters ranged from 1.34 to 1.70. Consistent with these results, age standardized HIV incidence rates were also highest in these clusters and estimated to be 10 or more per 100 PY. Compared to women 35+ years old younger women were more likely to reside in the highest incidence areas (aOR: 1·51, 95% CI: 1·06-2·15; aOR: 1.59, 95% CI: 1·19-2·14 and aOR: 1·62, 95% CI: 1·2-2·18 for < 20, 20-24, 25-29 years old respectively). Partnership factors (2+ sex partners and being unmarried/not cohabiting) were also more common in the highest incidence clusters (aOR 1.48, 95% CI: 1.25-1.75 and aOR 1.54, 95% CI: 1.28-1.84 respectively)., Conclusion: Fine geospatial analysis showed a continuous, unrelenting, hyper HIV epidemic in most of the greater Durban region with six communities characterised by particularly high levels of HIV incidence. The results motivate for comprehensive community-based HIV prevention approaches including expanded access to PrEP. In addition, a higher concentration of HIV related services is required in the highest risk communities to effectively reach the most vulnerable populations.

South Africa has the highest burden of human immunodeficiency virus (HIV) infections in the world with significant geographical variations. We identified the predictors of HIV infections and their sub-geographical-level contributions to the epidemic using a decade long data (2002-2012) from 6484 South African women. Generalized additive models were used to uncover the most significant features of these estimates across the region. In the overall analysis, younger age, not married or cohabiting with a partner, partner has another partner(s) and null/prim parity, using injectable contraceptives and presence of other sexually transmitted infections (STIs) were identified as independent predictors of HIV seroconversions. Overall, the top three highest contributors to infections were women's marital status (PAR% = 73%, 95% CI: 68%, 77%), parity (PAR% = 47%, 95% CI: 42%, 53%) and partnership factors (PAR% = 37%, 95% CI: 30%, 44%). However, their contributions varied remarkably at sub-geographical level. This was mainly due to the substantial localized variations in their prevalence and hazard ratios across the region. Our results will guide policy makers to develop tailored prevention strategies in order to allocate scarce resources by targeting the most significant contributors of HIV infection at sub-geographical level.

Background: A high endogenous progesterone luteal state in the menstrual cycle has been independently associated with Human Immunodeficiency Virus (HIV) incidence in epidemiological studies. Hormonal contraception particularly high dose Depot Medroxyprogesterone Acetate (DMPA) is also thought to increase the risk of HIV acquisition. Inconsistent reports of this association have led us to hypothesize that unsuppressed endogenous progesterone level in women who reported hormonal contraception (HC) use may be an explanation for increased vulnerability to HIV., Methods: This pilot study was a secondary cross-sectional analysis of data and laboratory testing of stored specimens collected from women who participated in the SAMRC HIV prevention MDP 301 trial during 2005-2009 in South Africa. Serum progesterone levels were measured in 39 women at the point of first positive HIV diagnosis during study follow-up and 36 women who remained HIV uninfected at the 52-week study exit visit., Results: Overall, the median (IQR) progesterone level in 49 women using hormonal contraception was 0.39 ng/ml (IQR 0.13-0.45) and 48 (97.9%) women had a progesterone level < 3.0 ng/ml suggestive of adequate progesterone suppression for contraceptive efficacy. After excluding the one woman with a progesterone level of > 3.0 ng/ml, the median progesterone level in women using DMPA remained marginally higher at 0.42 ng/ml (IQR 0.27-0.45) than women using Norethisterone Enanthate (NET-EN) (0.31 ng/ml; IQR 0.13-0.41, p = 0.061). For women using hormonal contraception, the median progesterone level did not differ between women with recent HIV infection or women who remained HIV negative (0.39 vs 0.38 ng/ml, p = 0.959). Similarly, the median progesterone level in women using DMPA or NET-EN did not differ by HIV status (0.43 vs 0.41 ng/ml, p = 0.905; 0.24 vs 0.31 ng/ml, p = 0.889)., Conclusion: Among women using hormonal contraception, DMPA or NET-EN we did not observe a significant difference in progesterone levels between women with recently acquired HIV infection and women who remained HIV negative. Our findings suggest that endogenous progesterone levels remain suppressed in the presence of hormonal contraception and are not likely to be associated with HIV acquisition.

Introduction: There are few data on the frequency of virological remission in African individuals after treatment with antiretroviral therapy (ART) in primary HIV infection (PHI)., Methods: We studied participants (n = 82) from South Africa and Uganda in Short Pulse Antiretroviral Treatment at HIV-1 Seroconversion, the first trial of treatment interruption in African individuals with PHI randomized to deferred ART or 48 weeks of immediate ART. All were female and infected with non-B HIV subtypes, mainly C. We measured HIV DNA in CD4+ T cells, CD4+ cell count, plasma viral load (pVL), cell-associated HIV RNA and T-cell activation and exhaustion. We explored associations with clinical progression and time to pVL rebound after treatment interruption (n = 22). Data were compared with non-African Short Pulse Antiretroviral Treatment at HIV-1 Seroconversion participants., Results: Pretherapy pVL and integrated HIV DNA were lower in Africans compared with non-Africans (median 4.16 vs. 4.72 log10 copies/ml and 3.07 vs. 3.61 log10 copies/million CD4+ T cells, respectively; P < 0.001). Pre-ART HIV DNA in Africans was associated with clinical progression (P = 0.001, HR per log10 copies/million CD4+ T cells increase (95% CI) 5.38 (1.95-14.79)) and time to pVL rebound (P = 0.034, HR per log10 copies/ml increase 4.33 (1.12-16.84)). After treatment interruption, Africans experienced longer duration of viral remission than non-Africans (P < 0.001; HR 3.90 (1.75-8.71). Five of 22 African participants (22.7%) maintained VL less than 400 copies/ml over a median of 188 weeks following treatment interruption., Conclusion: We find evidence of greater probability of virological remission following treatment interruption among African participants, although we are unable to differentiate between sex, ethnicity and viral subtype. The finding warrants further investigation.

Background: Women enrolled in human immunodeficiency virus (HIV) prevention efficacy trials receive counseling on prevention of HIV, sexually transmitted infections (STIs), and pregnancy during every visit. Incident pregnancy has an impact on efficacy outcomes. Incidence rates of pregnancy and HIV/STIs among women who became pregnant and associated risk factors were assessed., Methods: Data from 9165 women participating in HIV prevention trials in KwaZulu-Natal, South Africa from 2002-2012 were combined. Demographic and behavioral predictors of incidence pregnancy and incidence HIV and STIs were determined using Cox regression models., Results: Overall pregnancy incidence was 9.6 per 100 person-year (py) (95% confidence interval [Cl], 9.1-10.3). Human immunodeficiency virus incidence among pregnant women was 5.93 per 100 py (95% Cl, 4.73-7.44). Incidence of STIs among pregnant women for Chlamydia trachomatis, Trichomonas vaginalis, Neisseria gonorrhoeae, and Treponema pallidum (syphilis) were 10.87, 7.42, 3.92, and 1.43 per 100 py, respectively. In the adjusted analyses, we observed overlapping risk factors for HIV acquisition during pregnancy, ie, young age, not married/not cohabitating, and low parity. The risk of pregnancy and HIV acquisition is more than 3 times higher among young women (<20 years of age)., Conclusions: We identified overlapping risk factors for pregnancy and HIV incidence, suggesting an urgent need for appropriate, targeted, individual-centred counseling for women participating in HIV prevention trials.

Despite the salience of social support and violence as potential outcomes of disclosure, how pre-existing social support and relationship violence among people living with HIV shapes and influences HIV status disclosure has received limited attention. Following the Disclosure Process Model, this study investigated pre-disclosure support and violence-prone relationships as predictors of disclosure using data from a prospective study of 459 newly diagnosed South African women and men. Most (88%) disclosed their status to at least one person by their 8-month interview. Level of social support was unrelated to disclosure to a partner. However, those with higher levels of support had higher odds of disclosing to family and to others. Women in violence-prone relationships were more likely to report disclosure to a partner than were those not in such relationships, counter to expectations. The findings suggest that the same mechanisms may not explain processes of disclosure across all relationship types.

This article describes the influence of a peer education programme on skills development among 22 women participating in HIV prevention trials. Interviews were used to collect data on peer educator experiences and their opinions of the trainings. The training enhanced their agency and confidence to engage their family and community on health promotion, including HIV prevention research procedures, thus improving their self-esteem and communication skills. Training and partnering with clinical trial participants as peer educators is an effective and sustainable community-based approach for HIV prevention.

As oral tenofovir-based regimens for preexposure prophylaxis (PrEP) are adopted as standard of care for HIV prevention, their utilization in clinical trials among women in southern Africa will require an accurate estimate of oral PrEP efficacy in this population. This information is critical for women in choosing this prevention strategy, and in public health policy making. Estimates of the efficacy of oral PrEP regimens containing tenofovir have varied widely across trials that enrolled women, with some studies reporting high efficacy and others reporting no efficacy. Although poor adherence is strongly associated with lack of efficacy, other factors, such as mode of transmission (sexual vs. parenteral), predominant HIV subtype (C vs. non-C), intensity of exposure, and percentage of stable serodiscordant couples, may also contribute to the variation in efficacy estimates. In this article, we evaluate the evidence for PrEP efficacy in women and propose potential explanations for the observed differences in efficacy among studies. Our review emphasizes the need to continue to refine estimates of efficacy and effectiveness of tenofovir-based oral PrEP so as to best develop the next generation of HIV prevention tools, and to inform public policies directed toward HIV prevention.

Background: Women in sub-Saharan Africa are in urgent need of female-initiated human immunodeficiency virus (HIV) preventative methods. Vaginal rings are one dosage form in development for delivery of HIV microbicides. However, African women have limited experience with vaginal rings., Objectives: This Phase I, randomized, crossover trial assessed and compared the safety, acceptability and adherence of a silicone elastomer placebo vaginal ring, intended as a microbicide delivery method, inserted for a 12-week period in healthy, HIV-negative, sexually active women in South Africa and Tanzania., Methods: 170 women, aged 18 to 35 years were enrolled with 88 women randomized to Group A, using a placebo vaginal ring for 12 weeks followed by a 12-week safety observation period. 82 women were randomized to Group B and observed for safety first, followed by a placebo vaginal ring for 12 weeks. Safety was assessed by clinical laboratory assessments, pelvic/colposcopy examinations and adverse events. Possible carry-over effect was addressed by ensuring no signs or symptoms of genital irritation at crossover., Results: No safety concerns were identified for any safety variables assessed during the trial. No serious adverse events were reported considered related to the placebo vaginal ring. Vaginal candidiasis was the most common adverse event occurring in 11% of participants during each trial period. Vaginal discharge (2%), vaginal odour (2%), and bacterial vaginitis (2%) were assessed as possibly or probably related to the vaginal ring. Thirty-four percent of participants had sexually transmitted infections (STIs) at screening, compared to 12% of participants who tested positive for STIs at crossover and the final trial visit. Three participants (2%) tested HIV positive during the trial., Conclusions: The silicone elastomer vaginal ring had no safety concerns, demonstrating a profile favorable for further development for topical release of antiretroviral-based microbicides., Competing Interests: Data contained in this article were presented at the annual Conference on Retroviruses and Opportunistic Infections (CROI) 2011, Boston, USA, 27 Feb to 02 March 2011; and at the SA AIDS conference, Durban, SA, 07 to 10 June 2011. This trial was funded by International Partnership for Microbicides (IPM) (a not-for-profit public-private partnership). The role of the funder in the trial is as follows: IPM was responsible for trial design, implementation and data interpretation, the trial project management and oversight, site coordination, and trial monitoring. IPM was also responsible for in-house preparation of the clinical study report and manuscript. IPM provided the silicone elastomer vaginal rings used in this trial. Dr. Annaléne Nel, Ms. Neliëtte van Niekerk and Dr. Janine Martins are employees of IPM. With the exception of the above disclosure, the authors declare no further conflicts of interest. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Efforts to both characterize and eradicate the HIV reservoir have been limited by the rarity of latently infected cells and the absence of a specific denoting biomarker. CD32a (FcγRIIa) has been proposed to be a marker for an enriched CD4 T cell HIV reservoir, but this finding remains controversial. Here, we explore the expression of CD32 on CD3 + CD4 + cells in participants from two primary HIV infection studies and identify at least three distinct phenotypes (CD32 low , CD32 + CD14 + , and CD32 high ). Of note, CD4 negative enrichment kits remove the majority of CD4 + CD32 + T cells, potentially skewing subsequent analyses if used. CD32 high CD4 T cells had higher levels of HLA-DR and HIV co-receptor expression than other subsets, compatible with their being more susceptible to infection. Surprisingly, they also expressed high levels of CD20, TCRαβ, IgD, and IgM (but not IgG), markers for both T cells and naïve B cells. Compared with other populations, CD32 low cells had a more differentiated memory phenotype and high levels of immune checkpoint receptors, programmed death receptor-1 (PD-1), Tim-3, and TIGIT. Within all three CD3 + CD4 + CD32 + phenotypes, cells could be identified in infected participants, which contained HIV DNA. CD32 expression on CD4 T cells did not correlate with HIV DNA or cell-associated HIV RNA (both surrogate measures of overall reservoir size) or predict time to rebound viremia following treatment interruption, suggesting that it is not a dominant biomarker for HIV persistence. Our data suggest that while CD32 + T cells can be infected with HIV, CD32 is not a specific marker of the reservoir although it might identify a population of HIV enriched cells in certain situations.

Few studies have examined HIV-testing decision-making since the South African national HIV counseling and testing campaign in 2010-2011 and subsequent expansion in antiretroviral therapy (ART) eligibility in 2012. We describe HIV-testing decision-making and pathways to testing among participants in Pathways to Care, a cohort study of newly-diagnosed HIV-positive adults in KwaZulu-Natal. Our analysis is embedded within a theoretical framework informed by Arthur Kleinman's work on pluralistic healthcare systems, and the concept of diagnostic itineraries (i.e., the route taken to HIV testing). We conducted 26 semi-structured interviews in 2012, within one month of participants' diagnosis. Most (n = 22) deferred testing until they had developed symptoms, and then often sought recourse in non-biomedical settings. Of the eleven symptomatic participants who accessed professional medical services prior to testing, only three reported that a healthcare professional had offered or recommended an HIV test. Although ART emerged as an important motivator, offering hope of health and normalcy, fear of death and HIV-related stigma remained key barriers. Despite national policy changes in testing and treatment, health system and individual factors contributed to ongoing high levels of late diagnosis of HIV in this study population. Encouraging local health systems to direct clients toward HIV testing, and continuing to raise awareness of the benefits of routine testing remain important strategies to reduce delayed diagnoses.

We aimed to develop a HIV risk scoring algorithm for targeted screening among women in South Africa. We used data from five biomedical intervention trials (N = 8982 Cox regression models were used to create a risk prediction algorithm and it was internally and externally validated using standard statistical measures; 7-factors were identified as significant predictors of HIV infection: <25 years old, being single/not cohabiting, parity (<3), age at sexual debut (<16), 3+ sexual partners, using injectables and diagnosis with a sexually transmitted infection(s). A score of ≥25 (out of 50) was the optimum cut point with 83% (80%) sensitivity in the development (validation) dataset. Our tool can be used in designing future HIV prevention research and guiding recruitment strategies as well as in health care settings. Identifying, targeting and prioritising women at highest risk will have significant impact on preventing new HIV infections by scaling up testing and pre-exposure prophylaxis in conjunction with other HIV prevention modalities.

Background: Little is known regarding HIV disease outcomes among individuals who become infected with HIV while receiving antiretroviral medications for prevention. We compared HIV disease parameters among women who seroconverted while receiving tenofovir-containing oral or vaginal pre-exposure prophylaxis (PrEP) to placebo., Methods: Participants with HIV seroconversion in a randomized placebo-controlled trial of oral tenofovir, oral tenofovir/emtricitabine, and vaginal tenofovir gel (MTN-003) were followed in a longitudinal cohort study (MTN-015). The effect of oral and vaginal tenofovir-containing PrEP on HIV disease progression was compared to placebo using linear mixed effects and Cox proportional hazard models, as appropriate. Additional analyses were performed to compare the outcomes among participants with detectable tenofovir or emtricitabine in plasma at the first quarterly visit in MTN-003., Results: A total of 224 participants were included in the analysis; 93% from South Africa and 94% clade C virus. No differences in HIV RNA at steady state or the trajectory over 12 months were observed for each active arm compared to placebo; tenofovir gel recipients had higher CD4+ T cell counts (722 vs 596 cells/mm3; p = 0.02) at 90 days after estimated HIV seroconversion and higher average rates of change over 12 months compared to placebo (-181 vs -92 cells/mm3 per year; p = 0.08). With a median follow-up of 31 months, no significant differences were observed for time to CD4+ T cell count ≤350 cells/mm3, or the composite endpoint of CD4+ T cells ≤350 cells/mm3, initiation of antiretroviral therapy or death for each active arm compared to placebo. Additionally, there were no significant differences in the HIV RNA or CD4+ T cell counts at baseline, the change to month 12, or any disease progression outcomes among participants with oral drug detected and no oral drug detected compared to placebo., Conclusions: No clinically significant differences in HIV seroconversion outcomes were observed among women randomized to tenofovir-containing oral or vaginal PrEP regimens, however low overall adherence limits the generalizability of these findings.

The objective of this study was to describe the impact of intense counseling to reduce vaginal hygiene practices and its effect on bacterial vaginosis. A secondary data analysis of the HIV Prevention Trials Network 035 study was undertaken, focusing on HIV-negative, nonpregnant women who were at least 18 years old, in seven African sites and one US site. At enrollment and during follow-up quarterly visits, vaginal hygiene practices were determined by face-to-face administration of a behavioral assessment questionnaire. Vaginal hygiene practices were categorized as insertion into the vagina of (1) nothing, (2) water only, and (3) other substances with or without water. Each practice was quantified by frequency and type/combination of inserted substances. At quarterly visits, diagnosis of bacterial vaginosis was made using the Nugent score. Trends for vaginal hygiene practices and bacterial vaginosis were evaluated using generalized estimating equation models. A total of 3087 participants from the HIV Prevention Trials Network 035 study were eligible for this analysis. At enrollment, 1859 (60%) reported recent vaginal hygiene practices. By one year, this figure had decreased to 1019 (33%) with counseling. However, bacterial vaginosis prevalence remained consistent across the study observation period, with 36%-38% of women testing positive for the condition ( p for trend = 0.27). Overall, those who reported douching with water only (AOR = 1.03, 95%CI: 0.94-1.13) and those who reported inserting other substances (AOR= 0.98, 95%CI: 0.88-1.09) in the past quarter were not more likely to have bacterial vaginosis compared to those who reported no insertions. However, in South Africa, an increase in bacterial vaginosis was seen among those who reported inserting other substances (AOR: 1.48, 95%CI: 1.17, 1.88). In conclusion, targeted counseling against vaginal hygiene practices resulted in change in self-reported behavior but did not have an impact on bacterial vaginosis diagnosis in all but one site.

Sub-Saharan Africa has the highest number of HIV infected individuals in the world. Developing and implementing effective biomedical interventions still remains urgent. Poor adherence has been commonly identified as one of the major barriers for the success of HIV prevention trials. A better understanding of how to improve adherence remains a research priority. In this analysis, younger age (<35 years), number of children ≤2, being single/not cohabiting and having a new partner during the study follow up were all significantly associated with poor adherence and subsequent HIV seroconversions. At population level, these three factors collectively associated with 56 % of the low level adherence and 75 % of the HIV seroconversions. Results highlighted the importance of effective adherence and comprehensive contraceptive counselling of women who enrol in HIV prevention trials. Culturally and socially appropriate methods are needed to achieve and maintain optimum adherence levels in future HIV prevention research.

Background: Antiretroviral medications that are used as prophylaxis can prevent acquisition of human immunodeficiency virus type 1 (HIV-1) infection. However, in clinical trials among African women, the incidence of HIV-1 infection was not reduced, probably because of low adherence. Longer-acting methods of drug delivery, such as vaginal rings, may simplify use of antiretroviral medications and provide HIV-1 protection., Methods: We conducted a phase 3, randomized, double-blind, placebo-controlled trial of a monthly vaginal ring containing dapivirine, a non-nucleoside HIV-1 reverse-transcriptase inhibitor, involving women between the ages of 18 and 45 years in Malawi, South Africa, Uganda, and Zimbabwe., Results: Among the 2629 women who were enrolled, 168 HIV-1 infections occurred: 71 in the dapivirine group and 97 in the placebo group (incidence, 3.3 and 4.5 per 100 person-years, respectively). The incidence of HIV-1 infection in the dapivirine group was lower by 27% (95% confidence interval [CI], 1 to 46; P=0.046) than that in the placebo group. In an analysis that excluded data from two sites that had reduced rates of retention and adherence, the incidence of HIV-1 infection in the dapivirine group was lower by 37% (95% CI, 12 to 56; P=0.007) than that in the placebo group. In a post hoc analysis, higher rates of HIV-1 protection were observed among women over the age of 21 years (56%; 95% CI, 31 to 71; P<0.001) but not among those 21 years of age or younger (-27%; 95% CI, -133 to 31; P=0.45), a difference that was correlated with reduced adherence. The rates of adverse medical events and antiretroviral resistance among women who acquired HIV-1 infection were similar in the two groups., Conclusions: A monthly vaginal ring containing dapivirine reduced the risk of HIV-1 infection among African women, with increased efficacy in subgroups with evidence of increased adherence. (Funded by the National Institutes of Health; ClinicalTrials.gov number, NCT01617096 .).

Product sharing among participants can impact on adherence and compromise the outcome in clinical trials. We describe incidents of product sharing at the Durban clinical research sites conducting the VOICE trial. The Durban sites enrolled 2750 women with 1103 and 1647 participants randomized to the vaginal gel and oral tablet arms respectively. Monthly pill and applicator counts including product assessments were conducted by pharmacists. Discrepancies with product counts prompted discussions with participants. Thirty-two cases of product sharing were identified. Vaginal gels were more commonly shared than oral tablets. Product sharing between study participants and their female friends or relatives living in the same household was identified as the most common source of product sharing in this analysis. Study product counts and pharmacist-driven discussions with participants may help to identify reasons for product sharing and inform the development of strategies for PrEP implementation outside of the research setting. ClinicalTrials.gov number: NCT00705679.

A randomized, placebo-controlled, efficacy trial of Carraguard was unable to demonstrate a reduction in women's risk of HIV infection, which may have been due, in part, to low adherence (gel used in 42 % of vaginal sex acts, on average). A secondary analysis was undertaken to understand baseline factors associated with high adherence (gel used in ≥85 % of sex acts). Women who reported ≥1 vaginal sex act, returned ≥1 opened applicator, and had ≥1 conclusive post-enrollment HIV test (N = 5990) were included. Adherence was estimated as the ratio of average weekly applicator insertions (based on a dye stain assay indicating vaginal insertion)/average weekly sex acts (by self-report). Multivariate logistic regression modeling indicated that coital frequency, site, contraception, and partner age difference had a significant impact on adherence. Women reporting >1 and ≤2 vaginal sex acts per week, on average, were half as likely to be adherent as those reporting 1 vaginal sex act per week or less [adjusted odds ratio (AOR): 0.48; 95 % CI 0.38-0.61]; women from the Western Cape had one-third the odds of being adherent compared to women from KZN (AOR: 0.31; 95 % CI 0.23-0.41); compared to women using injectable contraception, women using any other or no method were more likely to be adherent (AOR: 1.30; 95 % CI 1.04-1.63); and women who had a larger age gap from their partners were more likely to be adherent (AOR: 1.03; 95 % CI 1.01-1.05; p = 0.001). Despite low adherence, overall, 13 % of participants achieved nearly perfect adherence, indicating a potential niche for a coitally dependent microbicide. More research is needed on the impact of sexual patterns and HIV risk perception on product acceptability and adherence to improve counseling in ongoing trials and when products are eventually introduced.

Background: Timely linkage to care by newly-diagnosed HIV+ individuals remains a significant challenge to achieving UNAIDS 90-90-90 goals. Current World Health Organization (WHO) guidelines recommend initiating anti-retroviral treatment (ART) regardless of CD4+ count, with priority given to those with CD4+ <350 cells/μl. We evaluated the impact of not having a day-of-diagnosis CD4+ count blood draw, as recommended by South African guidelines, on time to linkage, using data from a prospective cohort study., Methods: Individuals (N = 2773) were interviewed prior to HIV counseling and testing at three public sector primary care clinics in the greater Durban area; 785 were newly-diagnosed and eligible for the cohort study; 459 (58.5%) joined and were followed for eight months with three structured assessments. Linkage to care, defined as returning to clinic for CD4+ count results, and day-of-diagnosis blood draw were self-reported., Results: Overall, 72.5% did not have a day-of-diagnosis CD4+ count blood draw, and 19.2% of these never returned. Compared with a day-of-diagnosis blood draw, the adjusted hazard ratio of linkage (AHRlinkage) associated with not having day-of-diagnosis blood draw was 0.66 (95%CI: 0.51, 0.85). By 4 months, 54.8% of those without day-of-diagnosis blood draw vs. 75.2% with one were linked to care (chi-squared p = 0.004). Of those who deferred blood draw, 48.3% cited clinic-related and 51.7% cited personal reasons. AHRlinkage was 0.60 (95%CI: 0.44, 0.82) for clinic-related and 0.53 (95%CI: 0.38, 0.75) for personal reasons relative to having day-of-diagnosis blood draw., Conclusions: Newly-diagnosed HIV+ individuals who did not undergo CD4+ count blood draw on the day they were diagnosed-regardless of the reason for deferring-had delayed linkage to care relative to those with same-day blood draw. To enhance prompt linkage to care even when test and treat protocols are implemented, all diagnostic testing required before ART initiation should be performed on the same day as HIV testing/diagnosis. This may require modifying clinic procedures to enable overnight blood storage if same-day draws cannot be performed, and providing additional counseling to encourage newly-diagnosed individuals to complete day-of-diagnosis testing. Tracking HIV+ individuals via clinic registries should commence immediately from diagnosis to reduce these early losses to care., Competing Interests: The authors have declared that no competing interests exist.

Background: Total CD4 T-cell counts predict HIV disease progression but do not necessarily reflect normalization of immune function. CD4/CD8 ratio is a marker of immune dysfunction, a prognostic indicator for non-AIDS mortality, and reflects viral reservoir size. Despite antiretroviral therapy (ART), recovery of CD4/CD8 ratio in chronic HIV infection is incomplete; we hypothesize enhanced CD4/CD8 ratio recovery with earlier treatment initiation in recently infected individuals., Methods: CD4 count and CD4/CD8 ratio were analyzed using data from 2 cohorts: SPARTAC trial and the UK HIV Seroconverters Cohort where primary HIV infection (PHI) was defined as within 6 months from estimated date of infection. Using time-to-event methods and Cox proportional hazard models, we examined the effect of CD4/CD8 ratio at seroconversion on disease progression (CD4 <350 cells per cubic millimeter/ART initiation) and factors associated with time from ART initiation to CD4/CD8 normalization (ratio >1.0)., Findings: Of 573 seroconverters, 482 (84%) had abnormal CD4/CD8 ratios at HIV seroconversion. Individuals with higher CD4/CD8 ratio at seroconversion were significantly less likely to reach the disease progression endpoint [adjusted hazard ratio (aHR) (95% CI) = 0.52 (0.32 to 0.82), P = 0.005]. The longer the interval between seroconversion and ART initiation [HR (95% CI) = 0.98 per month increase (0.97, 0.99), P < 0.001], the less likely the CD4/CD8 ratio normalization. ART initiation within 6 months from seroconversion was significantly more likely to normalize [HR (95% CI) = 2.47 (1.67 to 3.67), P < 0.001] than those initiating later., Interpretation: Most individuals presenting in PHI have abnormal CD4/CD8 ratios. The sooner the ART is initiated in PHI, the greater the probability of achieving normal CD4/CD8 ratio.

In South Africa, a large proportion of young women are in age disparate relationships, which is believed to be a risk factor for human immunodeficiency virus (HIV). The aim of this study was to determine the generational effect of age disparity on HIV and sexually transmitted infection (STI) incidence. Socio-demographic and behavioural data were collected from women, aged 16 and older, who were followed for up to 24 months. Women who reported having a steady sexual partner older than themselves were categorised into: (1) non-age disparate partnerships (age difference between partners was 0-4 years); (2) intra-generational age disparate partnerships (5-9 year age gap between sexual partners); and (3) inter-generational age disparate partnerships (age gap of 10 years or more between sexual partners). Of the 1355 women included in the analysis, 759, 429 and 167 were in non-age disparate, intra-generational age disparate and inter-generational age disparate partnerships, respectively. Strong predictors of inter-generational age disparate partnerships include age, marital status and concurrency of sexual partners. No significant relationship between age disparity and risk of HIV acquisition was found. The highest crude STI incidence was observed among those in intra-generational age disparate relationships followed by those in non-age disparate relationships (31.86 [26.41-38.44] and 25.60 [21.92-29.91] per 100 person-years, respectively). Reduction of multiple partnerships remains key to HIV prevention; however, in light of partner concurrency being more prevalent than individual concurrency partnerships, female-initiated HIV prevention options remain critical., (© The Author(s) 2016.)

Introduction: No randomised controlled trial (RCT) has examined the efficacy of cotrimoxazole (CTX) prophylaxis in HIV-exposed uninfected (HEU) infants during the breastfeeding period, in this new era of effective prevention of mother-to-child transmission (PMTCT) prophylaxis. The efficacy of CTX prophylaxis has presently been demonstrated only in HIV-infected children. The absence of proven benefits in HEU breastfed infants associated with infectious diseases justifies an RCT as proposed. Herewith lies the rationale for conducting the proposed study., Methods: A partially blinded RCT is proposed to evaluate the efficacy of CTX prophylaxis administered from 6 weeks of age to HEU infants receiving a PMTCT regimen. A non-inferiority design will be used, randomising 1298 infants to receive CTX or not to receive CTX. Participants will be reviewed at the following time points: 6 weeks (enrolment and randomisation), 10 weeks, 14 weeks, 4 months and monthly thereafter until 12 months of age. They will be evaluated for anthropometric growth, interval illness, CTX adherence, signs and symptoms of study drug toxicity, concomitant medication use, breastfeeding status and HIV infection status. The study will compare the incidence of grade 3 and grade 4 common childhood illnesses (focusing on pneumonia and diarrhoea) and all-cause mortality until 12 months of age. In a subset of participants, we will compare grade 3 and grade 4 haemoglobin and alanine aminotransferase results as well as investigate gut integrity., Ethics and Dissemination: The study has ethical approval from the University of KwaZulu-Natal Biomedical Research Ethics Committee (BFC212/13)., Trial Registration Numbers: PACTR201311000621110 and DOH-27-0614-4728; Pre-results., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

We aimed to estimate the individual and joint impact of age, marital status and diagnosis with sexually transmitted infections (STIs) on HIV acquisition among young women at a population level in Durban, KwaZulu-Natal, South Africa. A total of 3,978 HIV seronegative women were recruited for four biomedical intervention trials from 2002-2009. Point and interval estimates of partial population attributable risk (PAR) were used to quantify the proportion of HIV seroconversions which can be prevented if a combination of risk factors is eliminated from a target population. More than 70% of the observed HIV acquisitions were collectively attributed to the three risk factors: younger age (<25 years old), unmarried and not cohabiting with a stable/regular partner and diagnosis with STIs. Addressing these risks requires targeted structural, behavioural, biomedical and cultural interventions in order to impact on unacceptably high HIV incidence rates among young women and the population as a whole.

Background: It is well documented that the mucosal linings of the female genital tract (FGT) usually provides a robust barrier that protects against sexually acquired infections. However, to the best of our knowledge there are limited South African studies that have investigated the association between damage to the mucosal linings and the acquisition of HIV infections. We hypothesize that in this cohort of women, a higher rate of HIV seroconversions will be observed for women who present with evidence of mucosal damage., Methods: We undertook a secondary analysis of the Methods for Improving Reproductive Health in Africa (MIRA) trial that assessed the effectiveness of the latex diaphragm and lubricant gel on HIV prevention among women. Participants underwent a physical examination which included a pelvic examination to detect the presence of mucosal abnormalities. During the physical examinations, the study clinicians examined the genitalia, cervix and vagina for signs of epithelial disruptions and abnormal vaginal discharge. The association between the various genital factors and HIV seroconversion was modeled using Cox proportional hazards regression analysis., Results: In this cohort of 1485 women that had enrolled to participate in the study, women that had presented with genital epithelial disruptions and abnormal vaginal discharge were shown to be at highest risk for HIV acquisition (Hazard Ratio (HR): 4.30, 95% CI: 2.25, 8.22, p <0001, HR: 2.37, 95% CI: 1.69, 3.33, p <0.001) respectively. In addition, the Kaplan Meier analysis showed that the highest number of seroconversions was observed in women that had disrupted genital epithelia (27 per 100/py, 95% CI: 15.0, 50.7) and abnormal vaginal discharge (12 per 100/py, 95% CI: 9.70, 16.7). Other significant factors included: genital signs and symptoms (HR: 1.67, 95% CI: 1.07, 2.61, p = 0.02) and genital ulcers/sores (HR: 1.79, 95% CI: 1.05, 3.06, p = 0.03)., Conclusion: We have shown that damage to the mucosal epithelial lining increases a women's risk of HIV seroconversion. Future studies that provide an in depth understanding of the mechanisms associated with the FGT and mucosal immunity will be most valuable. An understanding of all of these mechanisms will be key in directing the advancement of products most suitable for combating HIV infection in women., Trial Registration: This study was registered with ClinicalTrials.gov,number NCT00121459 on the 28th February 2007.

Background: Women in sub-Saharan Africa continue to be at greater risk for HIV acquisition than men. Concurrency, viz. multiple sexual partnerships that overlap over time, has been studied as a possible risk factor for HIV transmission. The aim of this study was to identify predictors of perceived male partner concurrency among sexually active, HIV negative women., Methods: Socio-demographic and behavioural data from women enrolled in a biomedical HIV prevention clinical trial were assessed in relation to perceived male partner concurrency using the Chi squared test. Univariate and multivariate logistic regression was performed to assess the independent predictors of perceived male partner concurrency. Kaplan-Meier survival estimates were obtained for HIV and STI incidence in relation to male partner concurrency. A Cox Proportional Hazards model was used to assess the association between perceived male partner concurrency and HIV and STI incidence., Results: The results revealed that 29 % of women reported their male partners to be in concurrent sexual relationships, 22 % reported partners that were not engaging in concurrency, whilst 49 % reported not knowing their partners concurrency status. Older women, having never married, experiencing economic abuse, and women reporting individual concurrency, were found to be significant predictors of perceived male partner concurrency in the studied population. Perceived male partner concurrency was not found to be a significantly associated with incident HIV and STI infections in this analysis., Conclusions: The study provides insight into predictors of perceived male partner concurrency among women at high risk for STI and HIV acquisition. These results may inform the design of behavioural and biomedical interventions, to address the role of multiple sexual partnerships in HIV prevention.

Background: Unplanned pregnancy rates in South Africa are high. Effective use of contraception is therefore an essential public health intervention to prevent unplanned pregnancies. This study describes contraception use and its impact on pregnancy in women participating in HIV prevention research and its implications for public health practice., Method: A secondary analysis of sociodemographic, behavioural, contraception use, and pregnancy incidence data was conducted amongst women participating in the Microbicides Development Programme (MDP) 301 trial conducted in Durban, South Africa. Log-rank tests were carried out to compare the pregnancy incidence between women who reported use of injectable contraceptive methods compared to women using oral contraceptive pills, using condoms and other methods (intrauterine device, traditional methods and natural methods). The effect of types of contraceptives on pregnancy incidence was assessed using Cox proportional hazards regression models., Results: Of the 2018 women enrolled, injectable contraception was the most commonly used method (52%) compared to pills, condoms for pregnancy prevention and other methods. Injectable contraception use was associated with lower crude pregnancy incidence of 4.4 per 100 woman-years [95% confidence interval (95% CI 3.3-5.9)] compared to women using pills [19.3 per 100 woman-years (95% CI 13.3-28.0)], condoms [19.7 per 100 woman-years (95% CI 16.3-23.6)] and other methods [11.5 per 100 woman-years (95% CI 7.5-17.6)]. This effect remained significant when adjusted for age, level of education, condom use at last sex act [hazard ratio 0.27, (95% CI 0.16-0.47, p<0.001)]., Conclusion: Injectable contraception offered a high level of protection against pregnancies among women in Durban., Trial Registration Number: ISRCTN64716212., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

Objective: To assess the effect of oral and injectable contraceptive use compared to nonhormonal contraceptive use on HIV acquisition among Southern African women enrolled in a microbicide trial., Study Design: This is a prospective cohort study using data from women enrolled in HIV Prevention Trials Network protocol 035. At each quarterly visit, participants were interviewed about self-reported contraceptive use and sexual behaviors and underwent HIV testing. Cox proportional hazards regression was used to assess the effect of injectable and oral hormonal contraceptive use on HIV acquisition., Results: The analysis included 2830 participants, of whom 106 became HIV infected (4.07 per 100 person-years). At baseline, 1546 (51%) participants reported using injectable contraceptives and 595 (21%) reported using oral contraceptives. HIV incidence among injectable, oral and nonhormonal contraceptive method users was 4.72, 2.68 and 3.83 per 100 person-years, respectively. Injectable contraceptive use was associated with a nonstatistically significant increased risk of HIV acquisition [adjusted hazard ratio (aHR)=1.17; 95% confidence interval (CI) 0.70, 1.96], while oral contraceptive use was associated with a nonstatistically significant decreased risk of HIV acquisition (aHR=0.76; 95% CI 0.37,1.55)., Conclusion: In this secondary analysis of randomized trial data, a marginal, but nonstatistically significant, increase in HIV risk among women using injectable hormonal contraceptives was observed. No increased HIV risk was observed among women using oral contraceptives. Our findings support the World Health Organization's recommendation that women at high risk for acquiring HIV, including those using progestogen-only injectable contraception, should be strongly advised to always use condoms and other HIV prevention measures., Implications: Among Southern African women participating in an HIV prevention trial, women using injectable hormonal contraceptives had a modest increased risk of HIV acquisition; however, this association was not statistically significant. Continued research on the relationship between widely used hormonal contraceptive methods and HIV acquisition is essential., (Copyright © 2016 Elsevier Inc. All rights reserved.)

While the expansion of antiretroviral therapy (ART) in sub-Saharan Africa has reduced morbidity and mortality from HIV/AIDS, it has increased concern about drug resistance. The Microbicide Trials Network 009 study assessed the prevalence of drug-resistance mutations among women at clinical sites in Durban, South Africa who tested seropositive for HIV-1 at screening for the VOICE trial. The objective of this paper was to identify characteristics and behaviors associated with drug resistance. Factors found to be significantly associated with increased resistance were high perceived risk of getting HIV and prior participation in a microbicide trial, a likely proxy for familiarity with the health care system. Two factors were found to be significantly associated with reduced resistance: having a primary sex partner and testing negative for HIV in the past year. Other variables hypothesized to be important in identifying women with resistant virus, including partner or friend on ART who shared with the participant and being given antiretrovirals during pregnancy or labor, or the proxy variable-number of times given birth in a health facility-were not significantly associated. The small number of participants with resistant virus and the probable underreporting of sensitive behaviors likely affected our ability to construct a comprehensive profile of the type of HIV-positive women at greatest risk of developing resistance mutations.

A recent analysis from South Africa reported no association between age-disparate relationships and HIV-1 acquisition. We assessed the association between male partner age and HIV-1 acquisition among South African women participating in the VOICE trial. Of 4077 women enrolled, 3789 had complete data; 26% and 5% reported having a partner >5 and >10 years older at enrollment, respectively. Reporting a partner >5 years older (hazard ratio = 1.00; 95% confidence interval: 0.74 to 1.35) or >10 older (hazard ratio = 0.92; 95% confidence interval: 0.49 to 1.74) was not associated with HIV-1 acquisition. These data corroborate recent reports and may suggest a shift in local epidemiology of heterosexual HIV-1 transmission.

Purpose of Review: This review was designed to evaluate the progress in studies of the use of oral and topical antiretroviral (ARV) medication for primary HIV prevention., Recent Findings: Nonhuman primate data have suggested that the administration of ARV medication before or after retroviral exposure can protect against the establishment of chronic infection. Over the past two decades, observational studies have demonstrated the safety of ARV agents for postexposure prophylaxis and more recent efficacy studies have demonstrated that tenofovir with or without emtricitabine can protect against HIV when used as preexposure prophylaxis (PrEP). Efficacy studies have been conducted in diverse populations, including men and transgender women who have sex with men, young African heterosexuals, and injection drug users. Three studies in African women evaluating oral and topical tenofovir-based regimens did not demonstrate efficacy, in large part because of suboptimal medication adherence. Further research is underway to determine the optimal ways to provide chemoprophylaxis, the optimal medications, and dosing regimens., Summary: PrEP can be effective in decreasing HIV transmission to at-risk uninfected persons, but further research is needed to determine the optimal modes of delivery., Competing Interests: Dr. Mayer has received unrestricted research grants from Gilead Sciences.

Background: Several observational studies have reported that HIV-1 acquisition seems to be higher in women who use depot medroxyprogesterone acetate (DMPA) than in those who do not use hormonal contraception. We aimed to assess whether two injectable progestin-only contraceptives, DMPA and norethisterone enanthate (NET-EN), confer different risks of HIV-1 acquisition., Methods: We included data from South African women who used injectable contraception while participating in theVOICE study, a multisite, randomised, placebo-controlled trial that investigated the safety and efficacy of three formulations of tenofovir for prevention of HIV-1 infection in women between Sept 9, 2009, and Aug 13, 2012. Women were assessed monthly for contraceptive use and incident infection. We estimated the difference in incident HIV-1infection between DMPA and NET-EN users by Cox proportional hazards regression analyses in this prospective cohort. The VOICE trial is registered with ClinicalTrials.gov, NCT00705679., Findings: 3141 South African women using injectable contraception were included in the present analysis: 1788 (56·9%)solely used DMPA, 1097 (34·9%) solely used NET-EN, and 256 (8·2%) used both injectable types at different times during follow-up. During 2733·7 person-years of follow-up, 207 incident HIV-1 infections occurred (incidence7·57 per 100 person-years, 95% CI 6·61–8·68). Risk of HIV-1 acquisition was higher among DMPA users (incidence 8·62 per 100 person-years, 95% CI 7·35–10·11) than among NET-EN users (5·67 per 100 person-years, 4·35–7·38;hazard ratio 1·53, 95% CI 1·12–2·08; p=0·007). This association persisted when adjusted for potential confoundingvariables (adjusted hazard ratio [aHR] 1·41, 95% CI 1·06–1·89; p=0·02). Among women seropositive for herpes simplex virus type 2 (HSV-2) at enrolment, the aHR was 2·02 (95% CI 1·26–3·24) compared with 1·09 (0·78–1·52)for HSV-2-seronegative women (pinteraction=0·07)., Interpretation: Although moderate associations in observational analyses should be interpreted with caution, thesefi ndings suggest that NET-EN might be an alternative injectable drug with a lower HIV risk than DMPA in high HIV-1 incidence settings where NET-EN is available., Funding: National Institutes of Health, Mary Meyer Scholars Fund, and the Ruth Freeman Memorial Fund.

Introduction: Understanding the impact of curable sexually transmitted infections (STIs) on HIV transmissibility is essential for effective HIV prevention programs. Investigating the impact of longitudinally measured recurrent STIs on HIV seroconversion is the interest of the current paper., Methods: In this prospective study, data from a total of 1456 HIV-negative women who enrolled in a HIV biomedical trial were used. It was hypothesized that women who had recurrent STI diagnoses during the study share a common biological heterogeneity which cannot be quantified. To incorporate this "unobserved" correlation in the analysis, times to HIV seroconversion were jointly modelled with repeated STI diagnoses using Cox regression with random effects., Results and Discussion: A total of 110 HIV seroconversions were observed (incidence rate of 6.00 per 100 person-years). In a multivariable model, women who were diagnosed at least once were more likely to seroconvert compared to those who had no STI diagnosis [hazard ratio (HR): 1.63, 95% confidence interval (CI): 1.04, 2.57]; women who had recurrent STI diagnoses during the study were 2.5 times more likely to be at increased risk of HIV infection (95% CI: 1.35, 4.01) with an estimated frailty variance of 1.52, with p<0.001, indicating strong evidence that there is a significant correlation (heterogeneity) among women who had recurrent STIs. In addition to this, factors associated with incidence of STIs, namely not being married and having a new sexual partner during the study follow-up, were all significantly associated with increased risk for HIV seroconversion (HR: 2.92, 95% CI: 1.76, 5.01 and HR: 2.25, 95% CI: 1.63, 3.83 respectively)., Conclusions: The results indicated that women who were at risk for STIs were also at risk of HIV infection. In fact, they share the similar risk factors. In addition to this, repeated STI diagnoses also increased women's susceptibility for HIV infection significantly. Decreasing STIs by increasing uptake of testing and treatment and reducing partner change plays a significant role in the trajectory of the epidemic.