Vaginal microbicides: where are we and where are we going?

The epidemic of HIV has catalyzed the need for safe and effective prevention methods, particularly for women. Vaginal microbicides have been targeted because these methods can be controlled by women themselves. Microbicides have focused on preventing HIV as well as other sexually transmitted infections, because the acquisition of HIV is enhanced by the presence of many infections. Although many products show promise in preclinical trials, safety remains paramount. The importance of safety was exemplified by the nonoxynol-9 studies which showed actual harm. This experience catalyzed the development of criteria that should be used as safety standards in trials, including immune markers of the cervical epithelium, and colposcopy standards. Unfortunately, immune markers are in their infant stages of development and reliability and validity checks remain large challenges. There have been four recent phase IIb/III trials that had disappointing results. However, these trials offer an opportunity to develop new preclinical models and biomarkers. The search for new microbicides remains critical. Current microbicides in trials can be categorized into vaginal defense enhancers (which help maintain the vaginal pH or facilitate the colonization of vaginal lactobacilli); surfactants (or detergents) which disrupt viral membranes; HIV entry inhibitors; and HIV reverse transcriptase inhibitors. Even with a good product, acceptance by both partners will be essential for its success, and lack of acceptance is often not evident until large trials are completed.