Use of a Vaginal Ring Containing Dapivirine for HIV-1 Prevention in Women

N Engl J Med. 2016 Dec 1;375(22):2121-2132. doi: 10.1056/NEJMoa1506110. Epub 2016 Feb 22.

Abstract

Background: Antiretroviral medications that are used as prophylaxis can prevent acquisition of human immunodeficiency virus type 1 (HIV-1) infection. However, in clinical trials among African women, the incidence of HIV-1 infection was not reduced, probably because of low adherence. Longer-acting methods of drug delivery, such as vaginal rings, may simplify use of antiretroviral medications and provide HIV-1 protection.

Methods: We conducted a phase 3, randomized, double-blind, placebo-controlled trial of a monthly vaginal ring containing dapivirine, a non-nucleoside HIV-1 reverse-transcriptase inhibitor, involving women between the ages of 18 and 45 years in Malawi, South Africa, Uganda, and Zimbabwe.

Results: Among the 2629 women who were enrolled, 168 HIV-1 infections occurred: 71 in the dapivirine group and 97 in the placebo group (incidence, 3.3 and 4.5 per 100 person-years, respectively). The incidence of HIV-1 infection in the dapivirine group was lower by 27% (95% confidence interval [CI], 1 to 46; P=0.046) than that in the placebo group. In an analysis that excluded data from two sites that had reduced rates of retention and adherence, the incidence of HIV-1 infection in the dapivirine group was lower by 37% (95% CI, 12 to 56; P=0.007) than that in the placebo group. In a post hoc analysis, higher rates of HIV-1 protection were observed among women over the age of 21 years (56%; 95% CI, 31 to 71; P<0.001) but not among those 21 years of age or younger (-27%; 95% CI, -133 to 31; P=0.45), a difference that was correlated with reduced adherence. The rates of adverse medical events and antiretroviral resistance among women who acquired HIV-1 infection were similar in the two groups.

Conclusions: A monthly vaginal ring containing dapivirine reduced the risk of HIV-1 infection among African women, with increased efficacy in subgroups with evidence of increased adherence. (Funded by the National Institutes of Health; ClinicalTrials.gov number, NCT01617096 .).

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial
  • Comment

MeSH terms

  • Adolescent
  • Adult
  • Africa, Southern / epidemiology
  • Age Factors
  • Double-Blind Method
  • Drug Resistance, Viral
  • Female
  • HIV Infections / epidemiology
  • HIV Infections / prevention & control*
  • HIV-1*
  • Humans
  • Incidence
  • Middle Aged
  • Patient Compliance
  • Pyrimidines / administration & dosage*
  • Pyrimidines / adverse effects
  • Reverse Transcriptase Inhibitors / administration & dosage*
  • Reverse Transcriptase Inhibitors / adverse effects
  • Vagina
  • Young Adult

Substances

  • Pyrimidines
  • Reverse Transcriptase Inhibitors
  • Dapivirine

Associated data

  • ClinicalTrials.gov/NCT01617096