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Background Limited data exists on effect of tenofovir (TDF) when used for Pre exposure prophylaxis (PrEP) on bone mineral density (BMD) in HIV negative women. We evaluated the effect of daily oral TDF and emtricitabine/TDF (FTC/TDF) compared to placebo on BMD among women enrolled in an HIV-1 PrEP trial. Methods HIV-uninfected women in Uganda and Zimbabwe had BMD measurements of lumbar spine (LS) and total hip (TH) via dual energy x-ray absorptiometry (DXA) at baseline and every 24 weeks for 48 weeks of active treatment and for 48 weeks after discontinuation of study medication. Plasma tenofovir levels were assessed every 12 weeks for the first 48 weeks. Results Of 518 women enrolled, 432 had DXA results at baseline and week 48. In the primary analysis, no significant differences in percent BMD change in hip or spine between arms observed, likely due to low product adherence. Among the subset with tenofovir detection in 75–100% of plasma samples, the mean percent BMD change from baseline to week 48 in the LS was 1.4% lower for TDF or FTC/TDF recipients than for placebo (p=0.002) and TH BMD was 0.9% lower (p=0.018). BMD changes from end of active treatment to 48 weeks were significantly greater in the active arm participants compared to placebo participants with a net difference of approximately +0.9% at the LS (p=0.007) and +0.7% (p=0.003) at the TH. Conclusion TDF-containing oral PrEP resulted in small but significant reversible decreases in hip and spine BMD among young African women.

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Nurses and peer counselors were not inferior in providing ART follow-up care to postpartum women, an approach that may help deliver treatment to many more HIV-infected people.

Background Despite the increasing frequency of ARV medicines stock-outs in Sub-Saharan Africa, there is little research inquiring into the mitigation strategies devised by frontline health facilities. Many previous studies have focused on ‘upstream’ or national-level drivers of ARVs stock-outs with less empirical attention devoted ‘down-stream’ or at the facility-level. The objective of this study was to examine the strategies devised by health facilities in Uganda to respond to the chronic stock-outs of ARVs. Methods This was a qualitative research design nested within a larger mixed-methods study. We purposively selected 16 health facilities from across Uganda (to achieve diversity with regard to; level of care (primary/ tertiary), setting (rural/urban) and geographic sub-region (northern/ central/western). We conducted 76 Semi-structured interviews with ART clinic managers, clinicians and pharmacists in the selected health facilities supplemented by on-site observations and documentary reviews. Data were analyzed by coding and thematic analyses. Results Participants reported that facility-level contributors to stock-outs include untimely orders of drugs from suppliers and inaccurate quantification of ARV medicine needs due to a paucity of ART program data. Internal stock management solutions for mitigating stock-outs which emerged include the substitution of ARV medicines which were out of stock, overstocking selected medicines and the use of recently expired drugs. The external solutions for mitigating stock-outs which were identified include ‘borrowing’ of ARVs from peer-providers, re-distributing stock across regions and upward referrals of patients. Systemic drivers of stock-outs were identified. These include the supply of drugs with a short shelf life, oversupply and undersupply of ARV medicines and migration pressures on the available ARVs stock at case-study facilities. Conclusion Health facilities devised internal stock management strategies and relied on peer-provider networks for ARV medicines during stock-out events. Our study underscores the importance of devising interventions aimed at improving Uganda’s medicines supply chain systems in the quest to reduce the frequency of ARV medicines stock-outs at the front-line level of service delivery. Further research is recommended on the effect of substituting ARV medicines on patient outcomes. Electronic supplementary material The online version of this article (10.1186/s12913-019-4137-7) contains supplementary material, which is available to authorized users.

Introduction: A vaginal ring containing 25 mg of the antiretroviral dapivirine has demonstrated efficacy in reducing women's risk of sexually acquiring HIV-1; however, imperfect ring use likely diluted efficacy estimates in clinical trials. The amount of dapivirine remaining in returned rings may reflect the extent of product use, permitting estimation of HIV protection in the context of consistent use. Methods: We measured the amount of dapivirine in returned rings from a placebo-controlled trial of the dapivirine vaginal ring conducted between August 2012 and June 2015 among 2629 African women. Phase I/II studies established that greater than 4 mg of dapivirine on average is released from the ring when used consistently over 28 days and ≤0.9 mg released suggested non-use. We assessed the relative risk reduction associated with levels of ring use using residual dapivirine in returned rings as a time-dependent covariate for HIV-1 infection in multivariable Cox models, including multiple exploratory analyses designed to estimate upper limits of efficacy given uncertainty in timing of HIV-1 acquisition. All models were adjusted for baseline covariates associated with HIV risk and adherence. Results: Residual dapivirine levels indicating at least some use (>0.9 mg released over a month) were associated with a 48% relative reduction in HIV-1 acquisition risk (95% confidence interval (CI): 21% to 66%; p = 0.002) compared to the placebo. Exploratory analyses accounting for potential misclassification in timing of HIV-1 acquisition estimated 75% to 91% HIV-1 risk reduction with> 4 mg released when compared to placebo. Results limited to the subgroup of women <25 years of age, who tended to have lower adherence, were generally consistent to those overall. Conclusions: Residual dapivirine levels, an objective measure of adherence, were correlated with HIV-1 protection in a secondary analysis of a randomized trial. Periods of ring use were associated with approximately 50% protection, with exploratory analyses suggesting higher protection with more consistent use. The dapivirine vaginal ring is the first method to fulfil the promise of a fully reversible, long-acting, woman-initiated approach for discreet HIV-1 prevention.

IntroductionWomen 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.MethodsASPIRE (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.ResultsBetween 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.ConclusionsAfrican 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.

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