A monthly vaginal ring (Ring-004), containing 25 mg dapivirine, was evaluated for safety and efficacy against HIV-1 infection in two large Phase III clinical trials, IPM 027 and MTN-020. Higher than anticipated HIV-1 incidence was observed and final safety and efficacy analyses were performed for IPM 027 prior to the planned completion of this time-driven trial based on an independent DSMB recommendation. The final results of IPM 027 at the data cut-off point of 16 October 2015 are reported.
IPM 027 is a Phase III, multi-centre, double-blind, randomized, placebo-controlled trial, conducted at six research centers in South Africa, and one center in Uganda to assess the safety and efficacy of dapivirine vaginal ring, inserted once every 4 weeks over 24 months, in healthy, sexually active HIV-negative women, 18 to 45 years of age. The primary efficacy endpoint was the rate of HIV-1 seroconversion and the primary safety endpoint was incidence of adverse events (AEs).
1959 women (1762 in South Africa and 197 in Uganda) were randomized in a 2:1 ratio to receive either a dapivirine ring or a placebo ring. The median age at enrolment was 25 years, and 91% were unmarried. At the data cut-off point, the total number of person years of follow-up was 2805 and 761 women had completed the two year follow-up period. A total of 133 post-randomization HIV-1 infections occurred: 77 among women assigned to dapivirine ring (incidence 4.08 per 100 person-years) and 56 among women assigned to placebo (incidence 6.10 per 100 person-years). Dapivirine vaginal ring reduced the risk of HIV-1 infection by 30.7% (95% CI: 0.90-51.5%; p=0.0401) relative to placebo. A 37.5% (95% CI: 3.5-59.5%) reduction in HIV-1 infection was observed in a subgroup analysis of women older than 21 years. Product-related AEs included metrorrhagia, menometrorrhagia, pelvic discomfort/pain, suprapubic pain and application site pain. The rate of AEs, including product-related AEs, urogenital AEs, serious AEs and deaths, was similar between treatment arms. Additional analyses of adherence to product use as measured by dapivirine levels in plasma and residual dapivirine levels in used rings will be presented.
Dapivirine Vaginal Ring-004 was safe and effective in preventing HIV-1 infection via vaginal intercourse in women in sub-Saharan Africa and may be an important HIV prevention option for women at risk of HIV infection.