Brief Report: Phase IIa Safety Study of a Vaginal Ring Containing Dapivirine in Adolescent Young Women
Katherine E Bunge, Lisa Levy, Daniel W Szydlo, Jingyang Zhang, Aditya H Gaur, Daniel Reirden, Kenneth H Mayer, Donna Futterman, Craig Hoesley, Sharon L Hillier, Mark A Marzinke, Craig W Hendrix, Pamina M Gorbach, Craig M Wilson, Lydia Soto-Torres, Bill Kapogiannis, Annalene Nel, Kathleen E Squires, MTN-023/IPM 030 Study Team, Katherine E Bunge, Lisa Levy, Daniel W Szydlo, Jingyang Zhang, Aditya H Gaur, Daniel Reirden, Kenneth H Mayer, Donna Futterman, Craig Hoesley, Sharon L Hillier, Mark A Marzinke, Craig W Hendrix, Pamina M Gorbach, Craig M Wilson, Lydia Soto-Torres, Bill Kapogiannis, Annalene Nel, Kathleen E Squires, MTN-023/IPM 030 Study Team
Abstract
Background: Young women aged 15-24 years are disproportionately affected by the HIV epidemic. Two phase III trials of a vaginal ring containing 25-mg dapivirine demonstrated HIV-1 risk reduction in adult women older than 21 years but not in those aged 18-21 years. Lack of protection was correlated with low adherence.
Methods: In this phase-IIa, randomized, double-blind, placebo-controlled, US, multicenter trial of the dapivirine ring in sexually active females, aged 15-17 years, participants were randomized 3:1 to a dapivirine or placebo ring to be inserted monthly for 6 months (NCT02028338). Primary safety end points included grade 2 product related adverse events and any grade 3 and higher adverse events. Adherence to ring use was assessed by plasma dapivirine concentrations, residual levels in used rings, and self-report. A plasma dapivirine concentration of >95 pg/mL was used to define short-term adherence; a residual ring level of <23.5 mg was used to define long-term adherence. Acceptability was assessed through computer-assisted self-interviews.
Results: Ninety-six participants were enrolled across 6 US sites. The median age was 16.0 years. There were no differences in safety outcomes between treatment arms. Adherence to the dapivirine ring was demonstrated by both plasma measurements (87%) and residual drug levels in rings (95%). Forty-two percent (95% confidence interval: 32 to 52) of participants reported that they never removed the ring. Participants noted no discomfort due to the ring at 87% of visits and "liking" the ring at 93% of visits.
Conclusion: The dapivirine vaginal ring, a promising topical microbicide, was well tolerated and acceptable in young US adolescents.
Conflict of interest statement
The authors declare no conflicts of interest.
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Source: PubMed