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

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 .).

• Authors: Jared M Baeten, Thesla Palanee-Phillips, Elizabeth R Brown, Katie Schwartz, Lydia E Soto-Torres, Vaneshree Govender, Nyaradzo M Mgodi, Flavia Matovu Kiweewa, Gonasagrie Nair, Felix Mhlanga, Samantha Siva, Linda-Gail Bekker, Nitesha Jeenarain, Zakir Gaffoor, Francis Martinson, Bonus Makanani, Arendevi Pather, Logashvari Naidoo, Marla Husnik, Barbra A Richardson, Urvi M Parikh, John W Mellors, Mark A Marzinke, Craig W Hendrix, Ariane van der Straten, Gita Ramjee, Zvavahera M Chirenje, Clemensia Nakabiito, Taha E Taha, Judith Jones, Ashley Mayo, Rachel Scheckter, Jennifer Berthiaume, Edward Livant, Cindy Jacobson, Patrick Ndase, Rhonda White, Karen Patterson, Donna Germuga, Beth Galaska, Katherine Bunge, Devika Singh, Daniel W Szydlo, Elizabeth T Montgomery, Barbara S Mensch, Kristine Torjesen, Cynthia I Grossman, Nahida Chakhtoura, Annalene Nel, Zeda Rosenberg, Ian McGowan, Sharon Hillier, MTN-020–ASPIRE Study Team
• Journal: The New England journal of medicine (N Engl J Med) Vol. 375 Issue 22 Pg. 2121-2132 (12 01 2016) ISSN: 1533-4406 [Electronic] United States
• PMID: 26900902 (Publication Type: Clinical Trial, Phase III, Journal Article, Multicenter Study, Randomized Controlled Trial, Comment)

Chemical References

• Pyrimidines
• Reverse Transcriptase Inhibitors
• Dapivirine

Topics

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