The development of rectal microbicides for HIV prevention.

INTRODUCTION: Individuals practicing unprotected receptive anal intercourse are at particularly high risk of HIV infection. Men who have sex with men in the developed and developing world continue to have disproportionate and increasing levels of HIV infection. The last few years have seen important progress in demonstrating the efficacy of oral antiretroviral pre-exposure prophylaxis, vaginal microbicides, and treatment as prevention, but there has also been significant progress in the development of rectal microbicides for HIV prevention. AREAS COVERED: The purpose of this review is to summarize the status of rectal microbicide research and to identify opportunities, challenges, and future directions in this important field of HIV prevention research. The design of completed and ongoing Phase I rectal microbicide studies that include the generation of comprehensive pharmacokinetic/pharmacodynamic data may allow for more rational decisions about which rectal microbicides should be advanced to later stage development. EXPERT OPINION: There is a strong rationale for the development of rectal microbicides for HIV prevention. Preclinical data provide supportive evidence for the feasibility of this approach, and there is significant interest in rectal microbicide development from communities at risk of HIV acquisition through unprotected receptive anal intercourse in both the developed and developing world. Demonstration of sustained safety, acceptability, and product adherence in the MTN-017 Phase II study of tenofovir 1% gel will be an important step in rectal microbicide development and will hopefully lead to Phase III effectiveness testing of this novel HIV prevention strategy.