Objective: To gain a greater understanding of published safety data for candidate vaginal microbicides.
Design: A systematic review of human safety trials of candidate vaginal microbicides – agents designed to protect women against HIV and other sexually transmitted infections.
Methods: Trials were published in peer-reviewed journals, and publication cut-off was August week 4, 2008. Trials of nonoxynol-9 were excluded, as were trials without a control group, trials that enrolled only male participants or reported on the investigation of a product for the treatment of a genital infection.
Results: Twenty-one trials of 11 products, involving 1465 women, satisfied review criteria. Most trials reported on genital epithelial findings and urogenital symptoms and a number reported a range of other local and systemic toxicity endpoints. Trials were generally of short duration (2 weeks or less) with small sample sizes. There were few findings of significant difference between women in active and control arms. Among the products assessed in more than one study, there were significantly more genital findings with intact epithelium in recipients of PRO2000 [relative risk (RR) 1.68, 95% confidence interval (CI) 1.08–2.60] and a lower incidence of bacterial vaginosis in dextrin sulphate recipients (RR 0.61, 95% CI 0.42–0.88). CIs were generally very wide, and most studies were unable to exclude differences of a substantial magnitude between treated and control women.
Conclusion: Larger and longer safety studies are necessary to detect clinically important toxicities, including those that indicate a potential increase in HIV risk, and provide assurance that agents are ready for large-scale effectiveness trials.
aUniversity of New South Wales, Australia
bChildren's Hospital at Westmead, Sydney, Australia
cFamily Health International, Arlington, Virginia, USA.
Received 4 September, 2008
Revised 5 January, 2009
Accepted 8 January, 2009
Correspondence to Professor John M. Kaldor, National Centre in HIV Epidemiology and Clinical Research, University of New South Wales, Level 2, 376 Victoria St, Darlinghurst 2010, NSW, Australia. Tel: +61 2 93850900; fax: +61 2 93850920; e-mail: email@example.com