Background A recent World Health Organization (WHO) technical consultation concluded that combined oral contraception (COC) does not increase HIV acquisition in women, but the evidence for depot medroxyprogesterone acetate (DMPA) is conflicting. Significant evidence suggests that bacterial vaginosis (BV) and vaginal candidiasis, both representing an ‘unhealthy’ vaginal microbiome, increase HIV acquisition in women.

Methods We conducted a systematic review using the PRISMA 2009 guidelines, and re-analysed the Hormonal Contraception and HIV Acquisition (HC-HIV) study, to evaluate the effect of HC use on the vaginal microbiome. Vaginal microbiome outcomes included BV by Nugent scoring, vaginal candidiasis by culture or KOH wet mount, and microbiome compositions as characterised by molecular techniques.

Results Our review of 36 eligible studies found that COC and DMPA use reduce BV 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% for each. In contrast, COC use (but not DMPA use) may increase vaginal candidiasis; 7 of 12 studies reported a statistically significant increase in vaginal candidiasis, 2 reported a positive association approaching significance, 2 reported no association, and one reported a statistically significant reduction. Evidence for a reduction of BV risk in HC users is much stronger than evidence for a potential increased candidiasis risk in COC users: the quality of the BV studies was higher and the results more consistent. 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 on the microbiome are less clear.

Conclusions The hypothesis that DMPA use may increase HIV risk by increasing BV or vaginal candidiasis risk is not supported by the evidence. COC use may predispose for vaginal candidiasis, but is not believed to be associated with increased HIV acquisition