Background: Young women ages 15-25 years are disproportionately affected by the HIV epidemic. Two phase 3 trials of a 25 mg dapivirine vaginal ring demonstrated HIV-1 risk reduction in adult women over 21, but not in those ages 18-21. Lack of protection was correlated with low adherence.
Methods: A Phase 2a randomized, double-blind, placebo-controlled trial of the dapivirine ring was conducted in sexually active females, ages 15-17. Participants were randomized 3:1 to a dapivirine or placebo ring to be inserted monthly for 6 months. Safety endpoints included grade 2 product-related adverse events (AE) and grade 3 and higher AEs. Adherence to ring use was assessed through self-report, plasma dapivirine concentrations and residual levels in used rings. A plasma dapivirine concentration > 95 pg/mL was used to define short- term adherence (hours); a dapivirine residual level < 23.5 mg was used to define long term adherence (monthly). Acceptability was assessed through computer assisted self-interviews.
Results: Ninety six participants were enrolled across six US sites. The mean age was 16.3 years; 59% were black and 34% white. Adherence to study visits was 97%. There were no differences in safety outcomes between treatment arms. By self-report 42% (95% CI 32, 52) of participants reported that they never removed the ring except to replace it monthly. In the dapivirine group, drug levels indicated adherence in 87% of plasma samples and 95% of rings. Participants noted no discomfort due to the ring at 87% of visits and “liking” the ring at 93% of visits. The most frequently cited concern (28%) involved their primary sex partner feeling the ring during sex.

Spaghetti Plot of Residual Dapivirine Concentratio
[Spaghetti Plot of Residual Dapivirine Concentratio]

Conclusions: The dapivirine vaginal ring, a promising microbicide approach, is safe and acceptable in this population. By self-report and objective measures, adherence was high. Discussing potential partner concerns with participants prior to ring use may positively influence adherence.