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N Engl J Med. 2016 Dec 1;375(22):2133-2143.

Safety and Efficacy of a Dapivirine Vaginal Ring for HIV Prevention in Women.

Collaborators (169)

Kruger S, Veldsman H, Van Vuuren LJ, Neate C, Mabuza N, De Villiers M, Masiu A, Masombuka L, Bodigelo C, Masilo R, Mema T, Mashigo J, Milanzi B, Olivier C, Martins M, Shibambu L, Phalali C, Motshweni D, Khoza B, Hlaletwa E, Kekana J, Mashabane S, Sibabela N, Mafoka M, Senne M, Khuzwayo L, Gwetu TP, Ngxongo M, Xulu S, Shabalala N, Lebenya T, Buthelezi S, Phakathi S, Naidoo M, Lembethe D, Nxele BR, Mlangeni MP, Mhlongo TG, Mkhize NN, Ndlovu G, Mabhida M, Dlamini T, Khanyile PQ, Mkhize S, Myeza B, Dlungwane TM, Tesfay NA, Ndlela JL, Ndlovu PS, Sosibo N, Sibiya S, Behariram S, Nkosi P, Felce J, Mhlongo M, Hills J, Sooknannan P, Groenewald B, Groenewald L, Ismail Z, Prethepal S, Sibisi T, Bell D, McMaster N, Schmuhl C, Mudeliar K, Mbuyisa L, Khanyile N, Dlamini N, Chonco V, Myeza T, Sithole M, Mabaso N, Thwala F, Mthethwa N, Mazibuko L, Hlongwane N, Zwane H, Hadebe N, Zondi V, Ndaba T, Mabizela P, Jele S, Thusi A, Mjiyakho N, Makhaya B, Khambule P, Ruzagira E, Basajja V, Nalutaaya S, Mawogole R, Joseph K, Henry S, Mugwaneza V, Rwanyonga R, Kesi DN, Taire P, Bahemuka U, Kibengo FM, Kalibbala M, Abaasa A, Aling E, Hughes P, Nakalema JI, Nakato S, Bayigga J, Onyango M, Namutosi FA, Kiyingi AW, Kabarambi A, Bahizi G, Nanyunja R, Collins KM, Nassuuna I, Masawi S, Ruth FN, Washi BK, Akankunda P, Nassimbwa S, Mayanja P, Mbabazi L, Bukenya AN, Kwizera M, Tumwiine JN, Christine N, Luyiga L, Aeron N, Vudriko TB, Edward M, Didas M, Witbooi L, Diedericks N, Naidoo K, Tobata P, Mahali O, Lifson L, Wallace J, Mncwabe N, Mcanjana N, Ntjana H, Mahoyi N, Ngetu N, Mithi B, Ntsadu B, Nkompela T, Ngqola B, Maqweqwana T, Gidana A, Seloka K, Dyani NW, Moraba R, de Boer L, Bolotini H, Mnqayi N, Mathe T, Hlathi M, Tema F, Ditshego C, Masemola S, Madihlaba S, Mokoena H, Mashishi A, Hlongoane J, Duvenhage L, Myeridricks R, Meyer R, Mohlala M, Mphake C, Masha M.

Author information

1
From International Partnership for Microbicides, Silver Spring, MD (A.N., N.N., H.C., B.D., M.I., M.M., W.M., J.N., M.R., S.N., M.S., L.S., P.S., J.S., K.W., Z.R.); London School of Hygiene and Tropical Medicine, London (S. Kapiga); Mwanza Intervention Trials Unit, Mwanza, Tanzania (S. Kapiga); Desmond Tutu HIV Centre, University of Cape Town, Cape Town (L.-G.B., K.G.), Maternal, Adolescent, and Child Health Research, Edendale (C.G., Z.M.), Qhakaza Mbokodo Research Clinic, Ladysmith (P.K.), Prevention for HIV and AIDS Project, Pinetown (N.M.), Madibeng Centre for Research, Brits, the Department of Family Medicine, Faculty of Health Sciences, University of Pretoria, Pretoria (C.L.), and Ndlovu Care Group, Elandsdoorn (H.T.) - all in South Africa; Medical Research Council-Uganda Virus Research Institute Research Unit on AIDS, Entebbe, Uganda (A.K., S. Kusemererwa); and SGS Life Science Services-Biometrics, Mechelen (M.B., S.R.), and Janssen Research and Development, Beerse (J.V.R., W.P., T.V., B.V.B.) - both in Belgium.

Abstract

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 .).

PMID:
27959766
DOI:
10.1056/NEJMoa1602046
[Indexed for MEDLINE]
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