Anti-Retroviral–Based HIV Pre-Exposure Prophylaxis for Women: Recent Advances and Next Steps

There is a daunting challenge to prevent human immunodeficiency virus (HIV) acquisition in women at high risk of acquiring HIV. Of the 37 million people globally living with HIV, more than half are women. Women account for nearly 60% of adults with HIV in sub-Saharan Africa, where unprotected heterosexual sex is the primary driver of the epidemic. While male condoms are effective, they are not always used, and this is not something women can control. Women urgently need prevention tools they can decide to use, independent of a husband or partner. Pre-exposure prophylaxis (PrEP), in which HIV-uninfected persons with ongoing HIV risk use antiretroviral (ARV) medications as chemoprophylaxis against sexual HIV acquisition, is a promising new HIV prevention strategy. We review recent advances in the development of new biomedical HIV prevention interventions with a highlight of findings from pivotal clinical trials, as well as a discussion on future generation strategies for women

Community Health Workers Improve HIV Disclosure Among HIV-Affected Sexual Partners in Rural Uganda : A Quasi-Experimental Study

Background: We evaluated the efficacy of a community health worker (CHW)–led intervention in supporting disclosure among adults living with HIV in heterosexual relationships. Methods: We conducted a quasi-experimental study with 2 arms allocated by geographically determined clusters and adjusted for between-group differences among adults living with HIV in the greater Luwero region of Uganda who had never disclosed their status to their current primary sexual partners. Clusters were allocated to either a CHW-led intervention or a control arm. In both arms, participants were consecutively recruited. As opposed to receiving routine care for the control arm, participants in the intervention arm received additional CHW disclosure support. The overall follow-up was 6 months, and the primary outcome was disclosure to the sexual partner. Data were analyzed using a clustered modified Poisson regression model with robust standard errors to determine independent factors associated with disclosure. Results: Of the 245 participants who enrolled, 230 (93.9%) completed the study, and 112 (48.7%) of those were in the intervention arm. The median age was 30 (interquartile range=25–37) years, the majority were women (76.5%), and most (80%) did not know their partners’ HIV status at study entry. At the end of follow-up, the overall disclosure prevalence was 74.4% (95% confidence interval [CI]=68.2, 79.9) and participants in the intervention arm were 51% more likely to disclose compared to those in the control (adjusted relative ratio [aRR]=1.51; 95% CI=1.28, 1.77). Men were 24% (aRR=1.24; 95% CI=1.07, 1.44) more likely to disclose compared to women, and membership in an HIV/AIDS association increased disclosure by 18% (aRR=1.18; 95% CI=1.01, 1.39). Conclusion: CHW support improved disclosure among adults living with HIV in heterosexual relationships when compared to routine care. Therefore, CHW-led mechanisms may be utilized in increasing disclosure among adults living with HIV in heterosexual relationships in rural settings

Vaginal ring use in a phase 3 microbicide trial: A comparison of objective measures and self-reports of non-adherence in ASPIRE

This analysis compares self-reports of product use with objective measures of non-adherence—quarterly plasma dapivirine levels and monthly residual dapivirine (DPV) levels in used rings—in MTN-020/ASPIRE, a phase 3 trial of a monthly DPV vaginal ring among women aged 18–45 years in Malawi, South Africa, Uganda and Zimbabwe. For participants on active product (N = 1211) we assessed self-reported monthly non-adherence, as measured by (1) whether the ring was ever out, and out for ≥ 12 h in the previous month and, (2) by a self-rating scale assessing ability to keep the vaginal ring inserted, and compared the self-reports to two biomarkers of non-use separately and as a composite measure. For this analysis, a plasma DPV value ≤ 95 pg/ml and residual ring ≥ 23.5 mg were used to classify non-adherence (i.e. the ring never being in the vagina the previous month). Compared to self-reports, non-adherence was found to be substantially higher for the composite measure as well as its two components, an indication that ring removal was likely underreported in the trial. The discrepancy between the self-report measure of ring outage and the composite indicator was greater for those aged 18–21 than for those older, evidence that younger women are more likely to underreport non-adherence. Despite underreporting of non-adherence, self-reports of the ring never being out were significant in predicting the composite objective measure. Furthermore, the association between the self-rating scale and the objective measure was in the expected direction and significant, although 11% of those 18–21 and 7% of those 22+ who rated their ability to keep the ring inserted as good, very good or excellent in the 4 weeks prior to exit were considered non-adherent according to the objective measure. This analysis indicates that while self-reports are significantly associated with objective measures of adherence in the ASPIRE trial, they were inflated—more so by those younger—and therefore may have limited utility identifying those who have challenges using products as directed

Brief Report: Impact of Antiretroviral Regimen on Pregnancy and Infant Outcomes in Women With HIV/ HBV Coinfection.

BackgroundThere are limited data on the impact of antenatal antiretroviral regimens (ARV) on pregnancy and infant outcomes in HIV/HBV coinfection. We compared outcomes among 3 antenatal antiretroviral regimens for pregnant women with HIV/HBV.MethodsThe PROMISE study enrolled ARV-naive pregnant women with HIV. Women with HBV were randomized to (no anti-HBV)-zidovudine (ZDV) + intrapartum nevirapine and 1 week of tenofovir disoproxil fumarate and emtricitabine (TDF-FTC); (3TC)-3TC + ZDV + LPV/r; or (FTC-TDF)-FTC + TDF + LPV/r. Pairwise group comparisons were performed with Fisher exact, t , or log rank tests. Adverse pregnancy outcome (APO) was a composite of low birth weight, preterm delivery, spontaneous abortion, stillbirth, or congenital anomaly.ResultsOf 138 women with HIV/HBV, 42, 48, and 48 were analyzed in the no anti-HBV, 3TC, and FTC-TDF arms. Median age was 27 years. APOs trended lower in the no anti-HBV (26%) vs 3TC (38%), and FTC-TDF arms (35%), P ≥ 0.25). More infant deaths occurred among the FTC-TDF [6 (13%)] vs no anti-HBV [2 (5%)] and 3TC [3 (7%)] arms. There were no differences in time-to-death, HIV-free survival, birth or one-year WHO Z-score length-for-age, and head circumference. Hepatitis B e antigen (HBeAg) was associated with an increased risk of APO, 48% vs 27% (odds ratio 2.79, 95% confidence interval: 1.19 to 6.67, post hoc ).ConclusionWith HBV/HIV coinfection, the risk of an APO was increased with maternal ARV compared with ZDV alone, although the differences were not statistically significant. Maternal HBeAg was associated with a significantly increased risk of APO. Infant mortality was highest with FTC + TDF + LPV/r. Early assessment of HBeAg could assist in identifying high-risk pregnancies for close monitoring

Brief report : dapivirine vaginal ring use does not diminish the effectiveness of hormonal contraception.

CAPRISA, 2017.Abstract available in pdf

Use of the dapivirine vaginal ring and effect on cervical cytology abnormalities.

ObjectiveWe aimed to determine if the dapivirine vaginal ring and the ring device alone (flexible silicone matrix polymer) was associated with the development of cervical cytology abnormalities.DesignSecondary analysis comparing cervical cytology results between two randomized controlled microbicide trials (MTN-020/ASPIRE and MTN-003/VOICE).MethodsData from ASPIRE, a phase III, placebo-controlled trial of the dapivirine vaginal ring, were used in this analysis. Cervical cytology smears were evaluated at baseline and at the final visit with product use. We compared cytology results between women randomized to dapivirine versus placebo vaginal ring. We further assessed for the effect of the vaginal ring device on cervical cytology by comparing results with data from the oral placebo arm of VOICE, a prior HIV-1 prevention trial conducted in a similar population.ResultsCervical cytology results for 2394 women from ASPIRE (1197 per study arm) were used in this analysis; median time between baseline and final visit with product use was 22.1 months. Cytology smear findings were comparable between dapivirine and placebo vaginal ring arms: at final visit, normal: 90.6 versus 91.5%, ASC-US//LSIL: 7.8 versus 7.4%, ASC-H/HSIL/AGC/AGC-favor neoplastic: 1.7 versus 1.1%, P = 0.44. Cytology data from VOICE had findings (normal: 87.8%, ASC-US/LSIL: 9.8%, ASC-H/HSIL/AGC/AGC-favor neoplastic: 2.4%) comparable with that of both dapivirine (P = 0.93) and placebo vaginal ring arms (P = 0.24).ConclusionThese findings indicate that neither use of the dapivirine vaginal ring nor the vaginal ring device alone, over a period of 2 years, is associated with development of cervical cytology abnormalities that could lead to precancerous or cancerous lesions

Characteristics of Women Enrolled into a Randomized Clinical Trial of Dapivirine Vaginal Ring for HIV-1 Prevention.

Women in sub-Saharan Africa are a priority population for evaluation of new biomedical HIV-1 prevention strategies. Antiretroviral pre-exposure prophylaxis is a promising prevention approach; however, clinical trials among young women using daily or coitally-dependent products have found low adherence. Antiretroviral-containing vaginal microbicide rings, which release medication over a month or longer, may reduce these adherence challenges.ASPIRE (A Study to Prevent Infection with a Ring for Extended Use) is a phase III, randomized, double-blind, placebo-controlled trial testing the safety and effectiveness of a vaginal ring containing the non-nucleoside reverse transcriptase inhibitor dapivirine for prevention of HIV-1 infection. We describe the baseline characteristics of African women enrolled in the ASPIRE trial.Between August 2012 and June 2014, 5516 women were screened and 2629 HIV-1 seronegative women between 18-45 years of age were enrolled from 15 research sites in Malawi, South Africa, Uganda, and Zimbabwe. The median age was 26 years (IQR 22-31) and the majority (59%) were unmarried. Nearly 100% of participants reported having a primary sex partner in the prior three months but 43% did not know the HIV-1 status of their primary partner; 17% reported additional concurrent partners. Nearly two-thirds (64%) reported having disclosed to primary partners about planned vaginal ring use in the trial. Sexually transmitted infections were prevalent: 12% had Chlamydia trachomatis, 7% Trichomonas vaginalis, 4% Neisseria gonorrhoeae, and 1% syphilis.African HIV-1 seronegative women at risk of HIV -1 infection were successfully enrolled into a phase III trial of dapivirine vaginal ring for HIV-1 prevention

Summary of subjects screened.

<p>Summary of subjects screened.</p

Participant characteristics¹.

<p>¹Note that the denominators used to calculate percentages throughout this table may vary owing to small amounts of missing data for individual variables and may not sum to 100% due to rounding.</p><p>² Based on a reactive result to the syphilis screening and a positive confirmatory test result. Note that participants testing positive at screening were provided treatment according to WHO guidelines.</p><p>Participant characteristics<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0128857#t002fn001" target="_blank">¹</a>.</p