Phase 1 Safety, Pharmacokinetics, and Pharmacodynamics of Dapivirine and Maraviroc Vaginal Rings: A Double-Blind Randomized Trial.

摘要: BACKGROUND Variable adherence limits effectiveness of daily oral and intravaginal tenofovir-containing pre-exposure prophylaxis. Monthly vaginal antiretroviral rings are one approach to improve drug delivery. METHODS MTN-013/IPM 026, a multisite, double-blind, randomized, placebo-controlled trial in 48 HIV-negative US women, evaluated containing dapivirine (DPV) (25 mg) maraviroc (MVC) (100 mg), DPV only, MVC placebo used continuously for 28 days. Safety was assessed by adverse events. Drug concentrations were quantified plasma, cervicovaginal fluid (CVF), cervical tissue. Cervical biopsy explants challenged with HIV ex vivo evaluate pharmacodynamics. RESULTS There no difference related genitourinary events between treatment arms compared placebo. rose higher initially before falling more rapidly the combination ring relatively stable single-drug rings. CVF 1 5 log10 greater than tissue plasma both consistently detected only CVF. dropped after removal. showed significant inverse linear relationship replication levels. CONCLUSIONS In this first study microbicide ring, all 4 safe well tolerated. Tissue 1000 times single had pharmacokinetics. DPV, but not MVC, demonstrated concentration-dependent inhibition HIV-1 infection Because detectable improved release is needed.