Kelley Colleen F, Acevedo-Quiñones Maribel, Agwu Allison L, Avihingsanon Anchalee, Benson Paul, Blumenthal Jill, Brinson Cynthia, Brites Carlos, Cahn Pedro, Cantos Valeria D, Clark Jesse, Clement Meredith, Creticos Cathy, Crofoot Gordon, Diaz Ricardo S, Doblecki-Lewis Susanne, Gallardo-Cartagena Jorge A, Gaur Aditya, Grinsztejn Beatriz, Hassler Shawn, Hinojosa Juan Carlos, Hodge Theo, Kaplan Richard, Lacerda Marcus, LaMarca Anthony, Losso Marcelo H, Valdez Madruga José, Mayer Kenneth H, Mills Anthony, Mounzer Karam, Ndlovu Nkosiphile, Novak Richard M, Perez Rios Alma, Phanuphak Nittaya, Ramgopal Moti, Ruane Peter J, Sánchez Jorge, Santos Breno, Schine Patric, Schreibman Tanya, Spencer LaShonda Y, Van Gerwen Olivia T, Vasconcelos Ricardo, Vasquez Jose Gabriel, Zwane Zwelethu, Cox Stephanie, Deaton Chris, Ebrahimi Ramin, Wong Pamela, Singh Renu, Brown Lillian B, Carter Christoph C, Das Moupali, Baeten Jared M, Ogbuagu Onyema
Hope Clinic of Emory University School of Medicine, Decatur, GA.
Grady Health System, Atlanta.
N Engl J Med. 2025 Apr 3;392(13):1261-1276. doi: 10.1056/NEJMoa2411858. Epub 2024 Nov 27.
BACKGROUND: Twice-yearly subcutaneous lenacapavir has been shown to be efficacious for prevention of human immunodeficiency virus (HIV) infection in cisgender women. The efficacy of lenacapavir for preexposure prophylaxis (PrEP) in cisgender men, transgender women, transgender men, and gender-nonbinary persons is unclear. METHODS: In this phase 3, double-blind, randomized, active-controlled trial, we randomly assigned participants in a 2:1 ratio to receive subcutaneous lenacapavir every 26 weeks or daily oral emtricitabine-tenofovir disoproxil fumarate (F/TDF). The primary efficacy analysis compared the incidence of HIV infection in the lenacapavir group with the background HIV incidence in the screened population. The secondary efficacy analysis compared the incidence of HIV infection in the lenacapavir group with that in the F/TDF group. RESULTS: Among 3265 participants who were included in the modified intention-to-treat analysis, HIV infections occurred in 2 participants in the lenacapavir group (0.10 per 100 person-years; 95% confidence interval [CI], 0.01 to 0.37) and in 9 participants in the F/TDF group (0.93 per 100 person-years; 95% CI, 0.43 to 1.77). The background HIV incidence in the screened population (4634 participants) was 2.37 per 100 person-years (95% CI, 1.65 to 3.42). The incidence of HIV infection in the lenacapavir group was significantly lower than both the background incidence (incidence rate ratio, 0.04; 95% CI, 0.01 to 0.18; P<0.001) and the incidence in the F/TDF group (incidence rate ratio, 0.11; 95% CI, 0.02 to 0.51; P = 0.002). No safety concerns were identified. A total of 26 of 2183 participants (1.2%) in the lenacapavir group and 3 of 1088 (0.3%) in the F/TDF group discontinued the trial regimen because of injection-site reactions. CONCLUSIONS: The HIV incidence with twice-yearly lenacapavir was significantly lower than the background incidence and the incidence with F/TDF. (Funded by Gilead Sciences; PURPOSE 2 ClinicalTrials.gov number, NCT04925752.).
背景：每半年一次皮下注射来那卡帕韦已被证明对预防顺性别女性感染人类免疫缺陷病毒（HIV）有效。来那卡帕韦用于顺性别男性、跨性别女性、跨性别男性和性别非二元者的暴露前预防（PrEP）的疗效尚不清楚。 方法：在这项3期双盲、随机、活性对照试验中，我们以2:1的比例将参与者随机分配，分别每26周接受一次皮下注射来那卡帕韦或每日口服恩曲他滨-替诺福韦酯富马酸盐（F/TDF）。主要疗效分析比较了来那卡帕韦组的HIV感染发生率与筛查人群中的背景HIV发生率。次要疗效分析比较了来那卡帕韦组与F/TDF组的HIV感染发生率。 结果：在纳入改良意向性分析的3265名参与者中，来那卡帕韦组有2名参与者发生HIV感染（每100人年0.10例；95%置信区间[CI]，0.01至0.37），F/TDF组有9名参与者发生HIV感染（每100人年0.93例；95%CI，0.43至1.77）。筛查人群（4634名参与者）中的背景HIV发生率为每100人年2.37例（95%CI，1.65至3.42）。来那卡帕韦组的HIV感染发生率显著低于背景发生率（发生率比，0.04；95%CI，0.01至0.18；P<0.001）和F/TDF组的发生率（发生率比，0.11；95%CI，0.02至0.51；P = 0.002）。未发现安全问题。来那卡帕韦组2183名参与者中有26名（1.2%）因注射部位反应而停用试验方案，F/TDF组1088名参与者中有3名（0.3%）因注射部位反应而停用试验方案。 结论：每半年一次使用来那卡帕韦的HIV发生率显著低于背景发生率和F/TDF的发生率。（由吉利德科学公司资助；PURPOSE 2临床试验注册号，NCT04925752。）
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