Background Pre-exposure prophylaxis (PrEP) is highly effective and an important prevention tool for African adolescent girls and young women (AGYW), but adherence and persistence are challenging. PrEP adherence support strategies for African AGYW were studied in an implementation study. Methods and findings HIV Prevention Trials Network (HPTN) 082 was conducted in Cape Town, Johannesburg (South Africa) and Harare (Zimbabwe) from October 2016 to October 2018 to evaluate PrEP uptake, persistence, and the effect of drug level feedback on adherence. Sexually active HIV–negative women ages 16–25 were offered PrEP and followed for 12 months; women who accepted were randomized to standard adherence support (counseling, 2-way SMS, and adherence clubs) or enhanced adherence support with adherence feedback from intracellular tenofovir-diphosphate (TFV-DP) levels in dried blood spots (DBS). PrEP uptake, persistence through 12 months (no PrEP hold or missed visits), and adherence were assessed. The primary outcome was high adherence (TFV-DP ≥700 fmol/punch) at 6 months, compared by study arm. Of 451 women enrolled, median age was 21 years, and 39% had curable sexually transmitted infections (STIs). Most (95%) started PrEP, of whom 55% had uninterrupted PrEP refills through 12 months. Of those with DBS, 84% had detectable TFV-DP levels at month 3, 57% at month 6, and 31% at month 12. At 6 months, 36/179 (21%) of AGYW in the enhanced arm had high adherence and 40/184 (22%) in the standard adherence support arm (adjusted odds ratio [OR] of 0.92; 95% confidence interval [CI] 0.55, 1.34; p = 0.76). Four women acquired HIV (incidence 1.0/100 person-years), with low or undetectable TFV-DP levels at or prior to seroconversion, and none of whom had tenofovir or emtricitabine resistance mutations. The study had limited power to detect a modest effect of incentives on adherence, and there was limited awareness of PrEP at the time the study was conducted. Conclusions In this study, PrEP initiation was high, over half of study participants persisted with PrEP through month 12, and the majority of young African women had detectable TFV-DP levels through month 6 with one-fifth having high adherence. Drug level feedback in the first 3 months of PrEP use did not increase the proportion with high adherence at month 6. HIV incidence was 1% in this cohort with 39% prevalence of curable STIs and moderate PrEP adherence. Strategies to support PrEP use and less adherence-dependent formulations are needed for this population. Trial registration ClinicalTrials.gov NCT02732730.

IntroductionHigh HIV incidence and low adherence to daily oral PrEP among women underscore the need for more acceptable and easier to use HIV prevention products. Global demand for injectable contraception suggests that new, long‐acting, injectable formulations could meet this need. We examine acceptability of a long‐acting injectable PrEP among HIV‐uninfected women in Zimbabwe, South Africa and two United States phase 2 trial sites.MethodsQuantitative surveys were administered at the first, fourth and sixth injection visits. Focus group discussions (FGD) were conducted after the sixth injection visit. We compared the acceptability of injectable product attributes, prevention preferences and future interest in injectable PrEP by site and arm and ran longitudinal ordinal logistic regression models to identify determinants of future interest in injectable PrEP.ResultsBetween April 2015 and February 2017, the trial enrolled 136 (100 African, 36 US) women with a median age of 31 years. Most participants (>75%) rated injectable attributes as very acceptable. While few reported rash or other side effects, 56% to 67% reported injection pain, with nonsignificant differences over time and between arms. During FGDs, participants described initial fear of the injectable and variable experiences with pain. Most US and African participants preferred injectable PrEP to daily oral pills (56% to 96% vs. 4% to 25%). Future interest in using injectable PrEP was associated with acceptability of product attributes and was higher in African than US sites. In FGDs, participants described multiple reasons for trial participation, including a combination of monetary, health‐related and altruistic motivations. While associated with future interest in use in univariate models, neither altruistic nor personal motivations remained significant in the multivariate model.ConclusionsThis study found that long‐acting injectable PrEP is acceptable among African and US women experiencing product use. Acceptability of product attributes better predicted future interest in injectable use than experience of pain. This is reassuring as a single‐dose regimen of a different product has advanced to phase 3 trials. Finally, the study suggests that future demand for an injectable PrEP by women may be greater in African than US settings, where the risk of HIV is highest.

BackgroundSerostatus disclosure may facilitate decreased HIV transmission between serodiscordant partners by raising risk awareness and heightening the need for prevention. For women living with HIV (WLWH), the decision to disclose may be influenced by culturally determined, community-level stigma and norms. Understanding the impact of community HIV stigma and gender norms on disclosure among WLWH in different countries may inform intervention development.MethodsHPTN063 was a longitudinal, observational study of sexually active HIV-infected individuals, including heterosexual women, in care in Zambia, Thailand and Brazil. At baseline, a questionnaire measuring community HIV stigma and gender norms, anticipated stigma, demographic, partner/relationship characteristics, and intimate partner violence was administered. Longitudinal HIV disclosure to sexual partners was determined via audio-computer assisted self-interview (ACASI) at the baseline and quarterly during the one year following up. Logistic regression was conducted to identify the predictors of disclosure.ResultsAlmost half (45%) of women living with HIV acknowledged perceived community HIV stigma (the belief that in their community HIV infection among women is associated with sex work and multiple sexual partners). Many women (42.9%) also acknowledged perceived community gender norms (the belief that traditional gender norms such as submissiveness to husbands/male sexual partners is necessary and that social status is lost if one does not procreate). HIV disclosure to current sex partners was reported by 67% of women. In multivariate analysis, among all women, those who were older [OR 0.16, 95%CI(0.06,0.48)], reported symptoms of severe depression [OR 0.53, 95%CI(0.31, 0.90)], endorsed anticipated stigma [OR 0.30, 95%CI(0.18, 0.50)], and were unmarried [OR 0.43, 95%CI(0.26,0.71)] were less likely to disclose to current partners. In an analysis stratified by marital status and cohabitation, unmarried [OR 0.41, 95%CI(0.20,0.82)] and non-cohabiting women [OR 0.31, 95%CI(0.13,0.73)] who perceived community HIV stigma were less likely to disclose to their sex partners.ConclusionsPerceived community level HIV stigma, along with individual level factors such as anticipated stigma, depressive symptoms, and older age, predict non-disclosure of HIV status to sexual partners among WLWH in diverse geographic settings. Interventions to promote disclosure among women in serodiscordant relationships should incorporate community-level interventions to reduce stigma and promote gender equality.

Background: Daily oral TDF/FTC is protective against HIV infection when used for pre-exposure prophylaxis (PrEP). However, daily adherence to oral PrEP is difficult for many; therefore, finding alternative PrEP strategies remains a priority. HPTN 076 evaluated the long-acting injectable form of rilpivirine (RPV), known as RPV LA for safety, pharmacokinetics and acceptability. Methods: HPTN 076 (NTC 02165202) was a phase 2, double-blind, 2:1 randomized trial comparing the safety of 1200mg RPV LA (LA) to placebo (P). The study included a 28-day oral run-in phase of daily, self-administered oral RPV (25 mg), with directly observed oral dosing about six times. Of 136 enrolled sexually active, HIV-uninfected, low HIV-risk African (100) and US (36) adult women, injectable product was administered in two gluteal, intramuscular (IM) injections once every eight weeks to 122 participants following the oral run-in phase. A maximum of six injection time points occurred over a 48-week period. Acceptability, safety, tolerability and pharmacokinetic (PK) data were collected throughout the study. This paper includes primary endpoint data collected up to the week 52 post enrollment. Findings: The median age of the enrolled population was 31 years (IQR: 25,38), median weight 75 kg (IQR: 64, 89), median body mass index (BMI) 30 (IQR: 27, 35), 46% married, 94% Black and 60% unemployed. A total of 122 (80 LA, 42 P) women received at least one injection and 98 (64 LA, 34 P) received all six injections. During the injection phase, three women withdrew from the study (2 LA, 1 P) and 16 women discontinued study product (10 LA, 6 P). Fourteen women (11 LA and 3 P) discontinued oral study product and did not enter the injection phase. Study product discontinuations were not significantly different between the two arms throughout. Of the product discontinuations in the injection phase, 8% in LA and 5% in P arm were due to adverse events (AEs), including one randomized to the P arm with prolonged QTc interval on EKG. The proportion of women who experienced Grade 2 or higher AEs during the injection phase as the primary outcome was not significantly different between the two arms [73.8%, 95% CI: (63.2%, 82.1%) for LA and 73.8%, 95% CI: (58.9%, 84.7%), p>0.99]. Transient Grade 2 liver abnormalities occurred in 14% of women in the LA arm compared with 12% in P arm. Three LA women (4%) developed Grade 3 injection site reactions compared with none in P arm. In participants who received at least 1 injection, the geometric mean of overall RPV trough concentrations (C trough ) was 62.2 ng/mL. In participants who received all six injections, the geometric mean of C Trough through the injection phase and after the last injection were 72.8 ng/mL and 100.9 ng/mL, respectively. At week 52 (eight weeks after last injection), the geometric mean of RPV C trough was 75.0 ng/mL. At the last injection visit (Week 44), 80 % of women who answered acceptability questions strongly agreed that they would think about using-and 68% that they would definitely use a Pr...