Microbicides and HIV prevention: lessons from the past, looking to the future

This review provides an update on developments in HIV microbicide research in the light of recent phase 3 efficacy studies and discusses how lessons learnt from early generation microbicide candidates can assist the development of future agents.

Results of an interim analysis of a phase 3 trial suggested that cellulose sulfate increased the risk of HIV acquisition compared with placebo. Carraguard, SAVVY and Buffergel also failed to show any HIV protection in human efficacy trials. Recent research has focused on elucidating the reasons behind these failures as well as improving the assessment of safety and efficacy for the next generation of microbicide candidates. PRO 2000 0.5% gel is the only HIV microbicide candidate for which there are preliminary data suggesting efficacy in women. Antiretroviral agents and entry inhibitors may provide the key in the future to developing an effective HIV microbicide both for vaginal and rectal use.

Development of a protective 'barrier' which can be controlled by the receptive partner independent of time of coitus remains a key goal in HIV prevention. A gel or ring-delivered combination of active anti-HIV agents may prove more efficacious than a single agent alone. Challenges in evaluating and manufacturing new candidates must be overcome before a well tolerated, effective, acceptable and affordable microbicide can be produced.