Advances in the Development of Microbicides for the Prevention of HIV Infection.

Microbicides are products that can be applied to vaginal or rectal mucosa with the intent of preventing, or at least significantly reducing, the transmission of sexually transmitted infections, including HIV-1. The past 2 or 3 years of microbicide research have generated several disappointments. Large, phase 2B/3 studies failed to demonstrate product efficacy, were stopped prematurely for futility, and in the worst-case scenario possibly demonstrated microbicide-induced harm. The most recently completed efficacy study (HPTN-035) did not reach statistical significance, but did show that use of PRO-2000 was associated with a 30% reduction in HIV acquisition. Current research focuses on much more potent targeted therapy, including reverse transcriptase inhibitors and CCR5 antagonists. Ongoing challenges include optimizing the identification of safety signals in phase 1/2 studies, defining a rationale for advancing products into efficacy studies, and identifying populations with adequate HIV seroincidence rates for these studies.