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Objective: A 2012 WHO consultation concluded that combined oral contraception (COC) does not increase HIV acquisition in women, but the evidence for depot medroxyprogesterone acetate (DMPA) is conflicting. We evaluated the effect of COC and DMPA use on the vaginal microbiome because current evidence suggests that any deviation from a 'healthy' vaginal microbiome increases women's susceptibility to HIV., Methods: We conducted a systematic review and reanalysed the Hormonal Contraception and HIV Acquisition (HC-HIV) study. Vaginal microbiome outcomes included bacterial vaginosis by Nugent scoring, vaginal candidiasis by culture or KOH wet mount and microbiome compositions as characterized by molecular techniques., Results: Our review of 36 eligible studies found that COC and DMPA use reduce bacterial vaginosis by 10-20 and 18-30%, respectively. The HC-HIV data showed that COC and DMPA use also reduce intermediate microbiota (Nugent score of 4-6) by 11% each. In contrast, COC use (but not DMPA use) may increase vaginal candidiasis. Molecular vaginal microbiome studies (n=4) confirm that high oestrogen levels favour a vaginal microbiome composition dominated by 'healthy' Lactobacillus species; the effects of progesterone are less clear and not well studied., Conclusion: DMPA use does not increase HIV risk by increasing bacterial vaginosis or vaginal candidiasis. COC use may predispose for vaginal candidiasis, but is not believed to be associated with increased HIV acquisition. However, the potential role of Candida species, and vaginal microbiome imbalances other than bacterial vaginosis or Candida species, in HIV transmission cannot yet be ruled out. Further in-depth molecular studies are needed.

As part of a prospective cohort study to assess HIV incidence among high-risk women in Kigali, Rwanda, we evaluated the association between high-risk human papillomavirus (HPV) infection and subsequent HIV acquisition. Women who seroconverted for HIV between the first and second HPV measurement visit were 4.9 times [95% confidence interval = 1.2-19.7] more likely to have HR-HPV detected at the first visit compared with women who remained HIV-negative.

Objective: To evaluate the safety, including impact on genital HIV RNA shedding, of Carraguard vaginal gel in HIV-infected women., Design: This is a randomized, controlled, crossover study of Carraguard in HIV-infected women in Thailand., Methods: Each woman (CD4 cell count 51-500 cells/microl and not on antiretroviral therapy) used each treatment (Carraguard, methylcellulose placebo, and no-product) once daily for 7 days during each 1-month period (3-week wash-out). Women were randomized to one of the six possible treatment sequences. Safety assessments were conducted at baseline (pregel), 15 min postgel, day 7, and day 14, and included HIV RNA measurements in cervicovaginal lavage (CVL) specimens., Results: Sixty women were enrolled, and 99% of scheduled study visits were completed. At baseline, median age (34 years), CD4 lymphocyte count (296 cells/microl), plasma HIV viral load (4.6 log10 copies/ml), CVL HIV viral load (3.1 log10 total copies per CVL), and sexual behaviors were similar among randomization groups. HIV viral load, leukocyte and hemoglobin levels, and epithelial cell counts in CVLs were lower 15 min after application of Carraguard or placebo compared with no product; CVL HIV viral load was still lower at day 7 but returned to baseline by day 14. Carraguard use was not associated with prevalent or incident genital findings or abnormal vaginal flora., Conclusion: Carraguard appears to be well tolerated for once-daily vaginal use by HIV-infected women. The observed reduction in CVL HIV viral load in the gel months may be clinically relevant but could have resulted from interference with sample collection by study gels.

Objectives: To assess the local and systemic safety of dapivirine vaginal gel vs. placebo gel as well as the systemic absorption of dapivirine in healthy, HIV-negative women., Methods: Two prospective, randomized, double-blind, placebo-controlled phase I/II studies were conducted at five research centers, four in Africa and one in Belgium. A total of 119 women used dapivirine gel (concentrations of 0.001, 0.002, 0.005, or 0.02%), and 28 used placebo gel twice daily for 42 days. The primary endpoints were colposcopic findings, adverse events, Division of AIDS grade 3 or grade 4 laboratory values, and plasma levels of dapivirine., Results: Safety data were similar for the dapivirine and placebo gels. None of the adverse events with incidence more than 5% occurred with greater frequency in the dapivirine than placebo groups. Similar percentages of placebo and dapivirine gel users had adverse events that were considered by the investigator to be related to study gel. A total of five serious adverse events occurred in the two studies, and none was assessed as related to study gel. Mean plasma concentrations of dapivirine were approximately dose proportional, and, within each dose group, mean concentrations were similar on days 7, 28, and 42. The maximum observed mean concentration was 474 pg/ml in the 0.02% gel group on day 28. Two weeks after the final application of study gel, mean concentrations decreased to 5 pg/ml or less., Conclusion: Twice daily administration of dapivirine vaginal gel for 42 days was safe and well tolerated with low systemic absorption in healthy, HIV-negative women suggesting that continued development is warranted.