Bekker, Linda-GailDas, MoupaliKarim, Quarraisha AbdoolAhmed, KhatijaBatting, JoanneBrumskine, WilliamGill, KatherineHarkoo, IshanaJaggernath, ManjeethaKigozi, GodfreyKiwanuka, NoahKotze, PhilipLebina, LimakatsoLouw, Cheryl E.Malahleha, MoeloManentsa, MmatsieMansoor, Leila E.Moodley, DhayendreNaicker, VimlaNaidoo, LogashvariNaidoo, MegeshineeNair, GonasagrieNdlovu, NkosiphilePalanee-Phillips, TheslaPanchia, RavindrePillay, SareshaPotloane, DiseboSelepe, PearlSingh, NishantaSingh, YashnaSpooner, ElizabethWard, Amy M.Zwane, ZwelethuEbrahimi, RaminZhao, YangKintu, AlexanderDeaton, ChrisCarter, Christoph C.Baeten, Jared M.Kiweewa, Flavia Matovu2025-05-302025-05-302024-10Bekker, L.G., Das, M. Karim, Q.A., Ahmed, K.,et al. 2024, 'Twice-yearly Lenacapavir or daily F/TAF for HIV prevention in cisgender women', New England Journal of Medicine, vol. 391, no. 13, pp. 1179-1192, doi : 10.1056/NEJMoa2407001.0028-4793 (print)1533-4406 (online)10.1056/NEJMoa2407001http://hdl.handle.net/2263/102590BACKGROUND : 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.en© 2024 Massachusetts Medical Society. All rights reserved.Reexposure prophylaxisHuman immunodeficiency virus (HIV)Cisgender womenHIV infectionLenacapavirPostprint Article