To assess the pharmacokinetics of dapivirine in plasma and dapivirine 
concentrations in cervicovaginal fluids (CVF) and cervicovaginal tissues 
following vaginal administration of dapivirine microbicide gel in healthy, 
HIV-negative women for 10 days. A randomized, double-blind, phase I study was 
conducted at a single research center in South Africa. A total of 18 women used 
dapivirine gel (0.001%, 0.005%, or 0.02%) once daily on Days 1 and 10 and twice 
daily on Days 2-9. Pharmacokinetics of dapivirine were assessed in plasma on 
Days 1 and 10. Dapivirine concentrations were measured in CVF on Days 1 and 10 
and in cervicovaginal tissues on Day 10. Safety was evaluated through laboratory 
tests (hematology, clinical chemistry, and urinalysis), physical examinations, 
and assessment of adverse events. Plasma concentrations of dapivirine increased 
over time with gel dose and were greater on Day 10 (C(max) 31 to 471 pg/ml) than 
Day 1 (C(max) 23 to 80 pg/ml). T(max) was 10-12 h on Day 1, and 9 h on Day 10. 
Concentrations in CVF generally increased with dose but were highly variable 
among participants. Mean peak values ranged from 4.6-8.3 × 10(6) pg/ml on Day 1 
and from 2.3-20.7 × 10(6) pg/ml on Day 10 across dose groups. Dapivirine was 
detectable in all tissue biopsies on Day 10 at concentrations of 1.0-356 × 10(3) 
pg/mg.
CONCLUSIONS: Dapivirine was widely distributed throughout the lower genital 
tract with low systemic absorption when administered in a vaginal gel 
formulation for 10 consecutive days. The gel was safe and well tolerated.