Protection of Rhesus Macaques from Vaginal Infection by Vaginally Delivered Maraviroc, an Inhibitor of HIV-1 Entry via the CCR5 Co-Receptor.
Veazey, Ronald S. 1; Ketas, Thomas J. 2; Dufour, Jason 1; Moroney-Rasmussen, Terri 1; Green, Linda C. 1; Klasse, P. J. 2; Moore, John P. 2
[Article] Journal of Infectious Diseases. 202(5):739-744, September 1, 2010.

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: An effective vaginal microbicide could reduce human immunodeficiency virus type 1 (HIV-1) transmission to women. Among microbicide candidates in clinical development is Maraviroc (MVC), a small-molecule drug that binds the CCR5 co-receptor and impedes HIV-1 entry into cells. Delivered systemically, MVC reduces viral load in HIV-1-infected individuals, but its ability to prevent transmission is untested. We have now evaluated MVC as a vaginal microbicide with use of a stringent model that involves challenge of rhesus macaques with a high-dose of a CCR5-using virus, SHIV-162P3. Gel-formulated, prescription-grade MVC provided dose-dependent protection, half-maximally at 0.5 mM (0.25 mg/mL). The duration of protection was transient; the longer the delay between MVC application and virus challenge, the less protection (half life of ~4 h). As expected, MVC neither protected against challenge with a CXCR4-using virus, SHIV-KU1, nor exacerbated postinfection viremia. These findings validate MVC development as a vaginal microbicide for women and should guide clinical programs.

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