Non-Antiretroviral Microbicides for HIV Prevention.

Non-antiretroviral microbicide candidates were previously explored as a female-controlled method of preventing sexual transmission of HIV. These products contained non-HIV specific active compounds that were ultimately found to disrupt the vaginal epithelium, cause increased immune activation in the female genital tract, disturb vaginal flora, and/or cause other irritation that precluded their use as vaginal microbicides. Due to the failure of these first-generation candidates, there was a shift in focus to developing HIV pre-exposure prophylaxis and microbicides containing small-molecule antiretrovirals. Even with the limited success of the antiretroviral-based microbicides in clinical evaluations and no commercially available products, there has been significant progress in microbicide research. The lessons learned from previous trials have given rise to more rigorous preclinical evaluation that aims to be better at predicting microbicide efficacy and safety and to novel formulation and delivery technologies. These advances have resulted in renewed interest in developing non-antiretroviral-based microbicides, such as broadly neutralizing antibodies (for example, VRC01) and anti-viral proteins (for example, Griffithsin), as options for persons not wanting to use antiretroviral drugs, and for their potential to prevent multiple sexually transmitted infections.