Because an effective vaginal or rectal microbicide could reduce the sexual transmission of HIV, much research is being conducted to discover the protection that various antiretroviral (ARV) agents could provide. Much of the information on use of ARV has emphasized the use of tenofovir (TFV) as a microbicidal agent. Over the past year maraviroc (MVC) has begun to be evaluated for use in this capacity.
Dr. John Moore presented data at CROI 2010 showing that topical MVC provided protection against HIV infection in female Rhesus Macaques (RM). MVC was prepared into a gel at various concentrations and inserted vaginally. The RM was then challenged with CCR5-using SHIV-162P3 virus. The duration of protection was transient; the longer the delay between MVC application and virus challenge the less protection. MVC gel was found to be half-maximally protective at 0.25mg/mL and fully protective at 3 mg/mL. At these concentrations a single 300mg tablet of MVC contains enough drug to protect 25 RM, deducing that women might similarly be protected from HIV for about $1 per application.
MVC was also shown to have good penetration to semen and rectal tissues in data presented by Kevin Brown. MVC was administered orally twice daily at 300mg doses for 8 days to male subjects. MVC concentrations were measured in blood, semen, and rectal tissue (via biopsy) at various time periods following administration of MVC. Semen concentrations were 38% lower than blood plasma levels following multiple doses; however, rectal tissue exposure after multiple dosing was 2-fold higher than blood plasma concentrations following multiple dosing. The finding of higher levels of MVC in rectal tissue is likely fecal elimination and mucous trapping of MVC.
Both of these studies point to continued development of MVC as a possible microbicide both vaginally and rectally to prevent the sexual transmission of HIV.
References:
John Moore et al. Protection of Rhesus Macaques from Vaginal Infection by Maraviroc, an Inhibitor of HIV-1 Entry via the CCR5 Co-receptor. Presented at 17th Conference on Retroviruses and Opportunistic Infections; San Francisco, CA. Oral Abstract 84LB.
Kevin Brown et al. Antiretroviral for Prevention: Maraviroc Exposure in the Semen and Rectal Tissue of Healthy Male Volunteers after Single and Multiple Dosing. Presented at 17th Conference on Retroviruses and Opportunistic Infections; San Francisco, CA. Oral Abstract 85.
02/18/10
PRN Report from 17th CROI: Maraviroc (MVC) for HIV Prevention
Source: Reporting from San Francisco for PRN News: A.C. Demidont, DO