The Safety, Persistence, and Acceptability of an Antiretroviral Microbicide Candidate UC781

Objective: To evaluate the persistence and acceptability of a minimally absorbed vaginal gel antiretroviral designed to block the acquisition of HIV. Methods: Sixty healthy women aged 18-45 participated in a phase-1 randomized placebo-controlled trial of a vaginal gel containing the non-nucleoside reverse transcriptase inhibitor UC781. Women underwent a single timed exposure ranging from 0 to 8 hours and were followed for 35 days. Safety was assessed by symptoms, physical exam, laboratory evaluation, and colposcopy. Persistence was assessed by drug levels in cervicovaginal lavage (CVL) and vaginal swab specimens. Results: The participants' mean age was 26 years; 77% were white. The most frequently reported adverse events were genitourinary; however, the placebo and UC781 arms had a similar distribution of mild and moderate genitourinary events. All colposcopic findings were superficial. Measuring systemic UC781 levels in the plasma revealed that 2 (5%) women in the UC781 gel group had detectable UC781; however, the amount was below the limits of quantification (2.5 ng/mL) in both participants. UC781 was detected in 37 of 40 CVL samples obtained 1-2 days after drug exposure and initial CVL; the median level of UC781 was 4965 pmol/mL, significantly higher than the known IC50 of 10 pmol/mL. Eighty percent of participants reported that they would use the product if it were found to be protective against HIV. Conclusion: In this population of HIV-uninfected women, the gel was well tolerated and acceptable. Active levels of drug were detected in CVL and vaginal swab specimens at 1-2 days at concentrations supporting the role for daily dosing.