Background: Two decades of research on topical microbicides for prevention of sexually transmitted infections (STIs) have had limited success. However, new microbicide randomised controlled trial (RCT) data have recently been published; but these have not yet been the subject of a systematic review.
Objectives: To determine the effects of topical microbicides for prevention of the acquisition of STIs, including human immunodeficiency virus (HIV) infection, by women from men and by men who have sex with men (MSM).
Search methods: In July 2011 we searched the Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, EMBASE, Web of Science, NLM Gateway, CLIB, AIDS Education Global Information System, ClinicalTrials.gov and the World Health Organization (WHO) International Clinical Trials Registry Platform; handsearched reference lists of relevant articles and contacted relevant organisations and experts.
Selection criteria: RCTs of topical microbicides (except Nonoxynol-9) in sexually active, HIV-negative women or MSM. We excluded Nonoxynol-9 because previous systematic reviews showed that it does not have a significant effect on HIV or STIs.
Data collection and analysis: We assessed study eligibility, extracted data and assessed risk of bias in duplicate; resolving differences by discussion and consensus. We then conducted fixed-effect meta-analysis, stratified by type of microbicide.
Main results: We found that by the end of 2011, nine microbicide RCTs had either been conducted to term (one BufferGel and 0.5% PRO 2000, one Carraguard and one tenofovir trial) or stopped early due to safety concerns (two cellulose sulphate trials) or insufficient rate of HIV infection and low likelihood of showing a protective effect (one 2% PRO 2000, one tenofovir and two SAVVY trials). The nine RCTs enrolled 31,941 sexually active women between 2004 and 2011; in Benin, Ghana, Malawi, Nigeria, South Africa, Tanzania, Uganda, Zambia, Zimbabwe, India, and the US. A small proof-of-concept RCT found that tenofovir (a nucleotide reverse transcriptase inhibitor) reduced the risk of HIV acquisition (one trial, 889 women; risk ratio (RR) 0.63; 95% CI 0.43 to 0.93). Effectiveness data are not yet available from the second tenofovir RCT that enrolled 5000 women and was stopped early due to low likelihood of showing a protective effect. We found no evidence of an effect on HIV acquisition for cellulose sulphate (2 trials, n = 3069; RR 1.20; 95% CI 0.74 to 1.95), SAVVY (two trials, n = 4295; RR 1.38; 95% CI 0.79 to 2.41), Carraguard (one trial, n = 6202; RR 0.89; 95% CI 0.71 to 1.11), PRO 2000 (two trials, n = 12,486; RR 0.93, 95% CI 0.77 to 1.14) and BufferGel (one trial, n = 1546; RR 1.05; 95% CI 0.73 to 1.52). Tenofovir reduced the incidence of herpes simplex virus type 2 (HSV-2) infection (one trial, 426 women; RR 0.55; 95% CI 0.37 to 0.83) and cellulose sulphate reduced the risk of chlamydia infection (two trials, n = 3069; RR 0.70, 95% CI 0.49 to 0.99). However, there was no evidence of an effect of any microbicide on the acquisition of gonorrhoea, syphilis, condyloma acuminatum, trichomoniasis, or human papillomavirus (HPV) infection. A substudy of the Carraguard trial found the prevalence of high-risk HPV infection (HR-HPV) to be 23.5% in women on Carraguard and 23.0% on placebo (n = 1718; RR 1.02; 95% CI 0.86 to 1.21). After controlling for HR-HPV risk factors, the authors found that compliant Carraguard users were 0.62 (95% CI 0.41 to 0.94) times as likely to be HR-HPV positive as compliant placebo users. Overall, there was no significant difference in the incidence of adverse events between microbicide and placebo groups.
Authors' conclusions: Limited evidence suggests that vaginal tenofovir microbicides may reduce the risk of acquisition of HIV and HSV-2 infections in women; but other types of topical microbicides have not shown evidence of an effect on HIV or STI acquisition. Therefore, there is not enough evidence to recommend topical microbicides for HIV or STI prevention at present. Further studies are needed to confirm the beneficial effects of tenofovir microbicide gel in vaginal sex. In addition, further research should continue on the development and testing of new microbicides. If the effectiveness of the tenofovir and/or other microbicides is confirmed in further studies, there will need to be a clear pathway to rapid regulatory approval. Successful launch of the effective gel would depend on having in place appropriate mechanisms for distribution to the women who need it, along with a strategy for ensuring that they use it correctly.