A step forward for HIV prevention in women

Safety and efficacy of a dapivirine vaginal ring for HIV prevention in women.

Nel A, van Niekerk N, Kapiga S, Bekker LG, Gama C, Gill K, Kamali A, Kotze P, Louw C, Mabude Z, Miti N, Kusemererwa S, Tempelman H, Carstens H, Devlin B, Isaacs M, Malherbe M, Mans W, Nuttall J, Russell M, Ntshele S, Smit M, Solai L, Spence P, Steytler J, Windle K, Borremans M, Resseler S, Van Roey J, Parys W, Vangeneugden T, Van Baelen B, Rosenberg Z; Ring Study Team. N Engl J Med. 2016 Dec;375(22):2133-2143.

Background: The incidence of human immunodeficiency virus (HIV) infection remains high among women in sub-Saharan Africa. We evaluated the safety and efficacy of extended use of a vaginal ring containing dapivirine for the prevention of HIV infection in 1959 healthy, sexually active women, 18 to 45 years of age, from seven communities in South Africa and Uganda.

Methods: In this randomized, double-blind, placebo-controlled, phase 3 trial, we randomly assigned participants in a 2:1 ratio to receive vaginal rings containing either 25 mg of dapivirine or placebo. Participants inserted the rings themselves every 4 weeks for up to 24 months. The primary efficacy end point was the rate of HIV type 1 (HIV-1) seroconversion.

Results: A total of 77 participants in the dapivirine group underwent HIV-1 seroconversion during 1888 person-years of follow-up (4.1 seroconversions per 100 person-years), as compared with 56 in the placebo group who underwent HIV-1 seroconversion during 917 person-years of follow-up (6.1 seroconversions per 100 person-years). The incidence of HIV-1 infection was 31% lower in the dapivirine group than in the placebo group (hazard ratio, 0.69; 95% confidence interval [CI], 0.49 to 0.99; P=0.04). There was no significant difference in efficacy of the dapivirine ring among women older than 21 years of age (hazard ratio for infection, 0.63; 95% CI, 0.41 to 0.97) and those 21 years of age or younger (hazard ratio, 0.85; 95% CI, 0.45 to 1.60; P=0.43 for treatment-by-age interaction). Among participants with HIV-1 infection, nonnucleoside reverse-transcriptase inhibitor resistance mutations were detected in 14 of 77 participants in the dapivirine group (18.2%) and in 9 of 56 (16.1%) in the placebo group. Serious adverse events occurred more often in the dapivirine group (in 38 participants [2.9%]) than in the placebo group (in 6 [0.9%]). However, no clear pattern was identified.

Conclusions: Among women in sub-Saharan Africa, the dapivirine ring was not associated with any safety concerns and was associated with a rate of acquisition of HIV-1 infection that was lower than the rate with placebo. (Funded by the International Partnership for Microbicides; ClinicalTrials.gov number, NCT01539226 .).

Abstract [1]  Full-text [free] access [2]

Editor’s notes: The need to develop safe, effective tools for women, particularly young women and adolescent girls, remains a high priority in sub-Saharan Africa. Self-inserted vaginal rings, which provide sustained release of antiretroviral drugs over time, offer an option that women can initiate themselves. Two large randomised trials have been conducted to assess the efficacy and safety of a vaginal ring containing dapivirine in preventing HIV infection in women. This trial is published in the same issue of the New England Journal of Medicine as the trial by Baeten et al [3]. (reviewed by HIV This Month in March 2016 [4]). Both trials were conducted in eastern and southern Africa where the incidence of HIV remains high.

As in the Baeten trial, this trial found a moderate reduction in HIV infection (31% lower) among women using the dapivirine vaginal ring compared with placebo. In both trials, protection was higher among women older than 21 years of age, although, unlike the Baeten trial, the difference in efficacy between the two age groups in this trial was not statistically significant. Baeten et al noted that biological measurement of adherence was higher among women older than 21 years (more than 70% overall) which may partly explain the higher protection observed. The investigators of both trials note that the genital tract of younger women may make them more susceptible to HIV infection. This warrants further investigation. Differences in the frequency of vaginal and/or anal sex across different age groups may also be important. In an editorial to accompany publication of these two important trials, Adimora [5] notes that “providers and women must ensure that the HIV interventions that women adopt match their sexual behaviours and needs. Different women – and women at different life stages – will require different types of HIV prevention.”  

Africa [10]
South Africa [11], Uganda [12]
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