Katherine E Bunge1, Lisa Levy2, Daniel W Szydlo3, Jingyang Zhang3, Aditya H Gaur4, Daniel Reirden5, Kenneth H Mayer6,7, Donna Futterman8, Craig Hoesley9, Sharon L Hillier1, Mark A Marzinke10, Craig W Hendrix10, Pamina M Gorbach11, Craig M Wilson9, Lydia Soto-Torres12, Bill Kapogiannis13, Annalene Nel14, Kathleen E Squires15,16. 1. Department of Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh, Pittsburgh, PA. 2. FHI 360, Durham, NC. 3. Fred Hutchinson Cancer Research Center- Statistical Center for HIV/AIDS Research and Prevention, Seattle, WA. 4. Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, TN. 5. Departments of Pediatrics and Internal Medicine, University of Colorado, Denver, CO. 6. The Fenway Institute, Boston, MA. 7. Department of Global Health and Population, Harvard University, Cambridge, MA. 8. Department of Pediatrics, Children's Hospital at Montefiore Medical Center, The Bronx, NY. 9. Department of Medicine, University of Alabama at Birmingham, Birmingham, AL. 10. Department of Medicine, Johns Hopkins University, Baltimore, MD. 11. Department of Epidemiology, University of California at Los Angeles Fielding School of Public Health, Los Angeles, CA. 12. National Institute of Allergy and Infectious Diseases, Division of AIDS, Bethesda, MD. 13. Maternal and Pediatric Infectious Disease Branch, National Institute of Child Health and Human Development, Bethesda, MD. 14. International Partnership for Microbicides, Silver Spring, MD. 15. Merck Research Labs, Rahway, NJ; and. 16. Department of Medicine, Sidney Kimmel Medical College of Thomas Jefferson University, Philadelphia, PA.
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.
RCT Entities:
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.
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