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: 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.