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

Baeten JM, Palanee-Phillips T, Brown ER, Schwartz K, Soto-Torres LE, Govender V, Mgodi NM, Matovu Kiweewa F, Nair G, Mhlanga F, Siva S, Bekker LG, Jeenarain N, Gaffoor Z, Martinson F, Makanani B, Pather A, Naidoo L, Husnik M, Richardson BA, Parikh UM, Mellors JW, Marzinke MA, Hendrix CW, van der Straten A, Ramjee G, Chirenje ZM, Nakabiito C, Taha TE, Jones J, Mayo A, Scheckter R, Berthiaume J, Livant E, Jacobson C, Ndase P, White R, Patterson K, Germuga D, Galaska B, Bunge K, Singh D, Szydlo DW, Montgomery ET, Mensch BS, Torjesen K, Grossman CI, Chakhtoura N, Nel A, Rosenberg Z, McGowan I, Hillier S.

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

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 .).

PMID: 26900902

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.