OPEN The New England journal of medicine | 24 Feb 2016
JM Baeten, T Palanee-Phillips, ER Brown, K Schwartz, LE Soto-Torres, V Govender, NM Mgodi, F Matovu Kiweewa, G Nair, F Mhlanga, S Siva, LG Bekker, N Jeenarain, Z Gaffoor, F Martinson, B Makanani, A Pather, L Naidoo, M Husnik, BA Richardson, UM Parikh, JW Mellors, MA Marzinke, CW Hendrix, A van der Straten, G Ramjee, ZM Chirenje, C Nakabiito, TE Taha, J Jones, A Mayo, R Scheckter, J Berthiaume, E Livant, C Jacobson, P Ndase, R White, K Patterson, D Germuga, B Galaska, K Bunge, D Singh, DW Szydlo, ET Montgomery, BS Mensch, K Torjesen, CI Grossman, N Chakhtoura, A Nel, Z Rosenberg, I McGowan and S Hillier
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=0.05) 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 .).
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