Objective-To compare single-and multiple-dose maraviroc exposures in cervicovaginal fluid (CVF) and vaginal tissue (VT) with blood plasma (BP) and quantify maraviroc protein binding in CVF.Design-Open-label pharmacokinetic study.Methods-In 12 HIV-negative women, 7 paired CVF and BP samples were collected over 12 hours after 1 maraviroc dose. Subjects then received maraviroc twice daily for 7 days. After the last dose, subjects underwent CVF and BP sampling as on day 1, with additional sampling during terminal elimination. VT biopsies were obtained at steady state.Results-Day 1 and day 7 median maraviroc CVF AUC τ were 1.9-and 2.7-fold higher, respectively, than BP. On day 1, 6 of 12 subjects had detectable maraviroc CVF concentrations within 1 hour; 12 of 12 were detectable within 2 hours, and all exceeded the protein-free IC 90 . On day 7, maraviroc CVF protein binding was 7.6% and the VT AUC τ was 1.9-fold higher than BP. Maraviroc CVF concentrations 72 hours after dose and BP concentrations 12 hours after dose were similar.Conclusions-Higher maraviroc exposure in the female genital tract provides a pharmacologic basis for further evaluation of chemokine receptor 5 antagonists in HIV infection prophylaxis. This is the first study to report antiretroviral VT concentrations, CVF protein binding, and CVF terminal elimination.

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