From 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.).
N Engl J Med. 2024 Oct 3;391(13):1179-1192. doi: 10.1056/NEJMoa2407001. Epub 2024 Jul 24.
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.
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.
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.
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.).
在顺性别女性中，艾滋病毒（HIV）预防的暴露前预防用药的使用率、坚持率和持续率存在差距。
我们进行了一项 3 期、双盲、随机、对照试验，纳入了南非和乌干达的青少年女孩和年轻女性。参与者以 2:2:1 的比例随机分配接受每 26 周皮下注射 lenacapavir、每日口服恩曲他滨替诺福韦艾拉酚胺（F/TAF）或每日口服恩曲他滨替诺福韦富马酸酯（F/TDF；阳性对照）；所有参与者还接受了交替的皮下或口服安慰剂。我们通过比较 HIV 感染的发生率与筛查人群中的估计背景发生率来评估 lenacapavir 和 F/TAF 的疗效，并评估与 F/TDF 相比的相对疗效。
在最初 HIV 阴性的 5338 名参与者中，观察到 55 例 HIV 感染：lenacapavir 组的 2134 名参与者中有 0 例感染（每 100 人年 0.00 例；95%置信区间 [CI]，0.00 至 0.19），F/TAF 组的 2136 名参与者中有 39 例感染（每 100 人年 2.02 例；95%CI，1.44 至 2.76），F/TDF 组的 1068 名参与者中有 16 例感染（每 100 人年 1.69 例；95%CI，0.96 至 2.74）。筛查人群（8094 名参与者）的背景 HIV 发生率为每 100 人年 2.41 例（95%CI，1.82 至 3.19）。lenacapavir 的 HIV 发生率明显低于背景 HIV 发生率（发病率比，0.00；95%CI，0.00 至 0.04；P<0.001）和 F/TDF 的 HIV 发生率（发病率比，0.00；95%CI，0.00 至 0.10；P<0.001）。F/TAF 的 HIV 发生率与背景 HIV 发生率无显著差异（发病率比，0.84；95%CI，0.55 至 1.28；P=0.21），也未观察到 F/TAF 和 F/TDF 之间 HIV 发生率有明显差异（发病率比，1.20；95%CI，0.67 至 2.14）。F/TAF 和 F/TDF 的依从性均较低。未发现安全问题。lenacapavir 组（68.8%）较安慰剂注射组（F/TAF 和 F/TDF 联合）（34.9%）更常发生注射部位反应；4 名 lenacapavir 组参与者（0.2%）因注射部位反应而停止试验方案。
没有接受每年两次 lenacapavir 治疗的参与者感染 HIV。lenacapavir 的 HIV 发生率明显低于背景 HIV 发生率和 F/TDF 的 HIV 发生率。（由吉利德科学公司资助；PURPOSE 1 临床试验.gov 编号，NCT04994509。）
