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Twice-Yearly Lenacapavir or Daily F/TAF for HIV Prevention in Cisgender Women
Linda-Gail Bekker1, Moupali Das1, Quarraisha Abdool Karim1
1From the Desmond Tutu HIV Centre (L.-G.B., K.G., G.N., Y.S.) and the Department of Medicine, Vuka Research Clinic (A.M.W.), University of Cape Town, Cape Town, the Department of Epidemiology and Prevention, Centre for the AIDS Programme of Research in South Africa (Q.A.K.), Centre for the AIDS Programme of Research in South Africa, University of KwaZulu-Natal (I.H., L.E.M., D.M., M.N., D.P.), the Department of Obstetrics and Gynaecology, Wits Maternal, Adolescent, and Child Health Research Unit, University of the Witwatersrand (M.J.), Africa Health Research Institute (L.L.), and the HIV and Other Infectious Diseases Research Unit, South African Medical Research Council (V.N., L.N., S.P., N.S., E.S.), Durban, Setshaba Research Centre, Tshwane City (K.A.), the Department of Medical Microbiology, School of Medicine, Faculty of Health Sciences, University of Pretoria (K.A.), and the Aurum Institute, Pretoria Clinical Research Site (Z.Z.), Pretoria, the Foundation for Professional Development, Ndevana Community Research Site (J.B.), and Synergy Biomed Research Institute (M. Malahleha), East London, the Clinical Research Division, the Aurum Institute, Rustenburg (W.B.), Qhakaza Mbokodo Research Clinic (P.K.) and La Verna Hospital (P.K.), Ladysmith, Madibeng Centre for Research, Brits (C.E.L.), the Aurum Institute (M. Manentsa) and Wits Reproductive Health and HIV Institute, Faculty of Health Sciences, School of Public Health, University of the Witwatersrand (N.N., T.P.-P.), Johannesburg, the Perinatal HIV Research Unit, Kliptown-Aeroton Clinical Research Site, University of the Witwatersrand, Soweto (R.P.), and the Aurum Institute, Klerksdorp Clinical Research Site, Klerksdorp (P.S.) - all in South Africa; Gilead Sciences, Foster City, CA (M.D., R.E., Y.Z., A.K., C.C.C., J.M.B.); the Department of Epidemiology, Columbia University Mailman School of Public Health, New York (Q.A.K.); the Department of Medicine, Vanderbilt University, Nashville (W.B.); Africa Medical and Behavioral Sciences Organization, Kalisizo (G.K.), the Department of Epidemiology and Biostatistics, Makerere University School of Public Health (N.K., F.M.K.), and Makerere University-Johns Hopkins University Research Collaboration (F.M.K.), Kampala - all in Uganda; the Department of Epidemiology, School of Public Health, University of Washington, Seattle (T.P.-P.); and Gilead Sciences, Cambridge, United Kingdom (C.D.).
Background:
There are gaps in uptake of, adherence to, and persistence in the use of preexposure prophylaxis for human immunodeficiency virus (HIV) prevention among cisgender women.
Methods:
We conducted a phase 3, double-blind, randomized, controlled trial involving adolescent girls and young women in South Africa and Uganda. Participants were assigned in a 2:2:1 ratio to receive subcutaneous lenacapavir every 26 weeks, daily oral emtricitabine-tenofovir alafenamide (F/TAF), or daily oral emtricitabine-tenofovir disoproxil fumarate (F/TDF; active control); all participants also received the alternate subcutaneous or oral placebo. We assessed the efficacy of lenacapavir and F/TAF by comparing the incidence of HIV infection with the estimated background incidence in the screened population and evaluated relative efficacy as compared with F/TDF.
Results:
Among 5338 participants who were initially HIV-negative, 55 incident HIV infections were observed: 0 infections among 2134 participants in the lenacapavir group (0 per 100 person-years; 95% confidence interval [CI], 0.00 to 0.19), 39 infections among 2136 participants in the F/TAF group (2.02 per 100 person-years; 95% CI, 1.44 to 2.76), and 16 infections among 1068 participants in the F/TDF group (1.69 per 100 person-years; 95% CI, 0.96 to 2.74). Background HIV incidence in the screened population (8094 participants) was 2.41 per 100 person-years (95% CI, 1.82 to 3.19). HIV incidence with lenacapavir was significantly lower than background HIV incidence (incidence rate ratio, 0.00; 95% CI, 0.00 to 0.04; P<0.001) and than HIV incidence with F/TDF (incidence rate ratio, 0.00; 95% CI, 0.00 to 0.10; P<0.001). HIV incidence with F/TAF did not differ significantly from background HIV incidence (incidence rate ratio, 0.84; 95% CI, 0.55 to 1.28; P = 0.21), and no evidence of a meaningful difference in HIV incidence was observed between F/TAF and F/TDF (incidence rate ratio, 1.20; 95% CI, 0.67 to 2.14). Adherence to F/TAF and F/TDF was low. No safety concerns were found. Injection-site reactions were more common in the lenacapavir group (68.8%) than in the placebo injection group (F/TAF and F/TDF combined) (34.9%); 4 participants in the lenacapavir group (0.2%) discontinued the trial regimen owing to injection-site reactions.
Conclusions:
No participants receiving twice-yearly lenacapavir acquired HIV infection. HIV incidence with lenacapavir was significantly lower than background HIV incidence and HIV incidence with F/TDF. (Funded by Gilead Sciences; PURPOSE 1 ClinicalTrials.gov number, NCT04994509.).
