Twice-Yearly Lenacapavir for HIV Prevention in Men and Gender-Diverse Persons.

Nkosiphile Ndlovu, Jill Blumenthal, Jesse Clark, Meredith Clement, Cathy Creticos, Ricardo S Diaz, Susanne Doblecki-Lewis, Jorge A Gallardo-Cartagena, Shawn Hassler, Juan Carlos Hinojosa, Theo Hodge, Marcus Lacerda, Anthony LaMarca, José Valdez Madruga, Paul Benson, Alma Perez Rios, Patric Schine, Tanya Schreibman, LaShonda Y Spencer, Olivia T Van Gerwen, Ricardo Vasconcelos, Jose Gabriel Vasquez, Zwelethu Zwane, Stephanie Cox, Chris Deaton, Lillian B Brown, Christoph C Carter, Onyema Ogbuagu, Peter J Ruane, Moupali Das, Breno Santos, Ramin Ebrahimi, Marcelo H Losso, Nittaya Phanuphak, Carlos Brites, Karam Mounzer, Cynthia Brinson, Renu Singh, Pedro Cahn, Pamela Wong, Gordon Crofoot, Richard Kaplan, Colleen F Kelley, Anthony Mills, Aditya Gaur, Moti Ramgopal, Beatriz Grinsztejn, Jorge Sánchez, Richard M Novak, Kenneth H Mayer, Anchalee Avihingsanon, Valeria D Cantos, Jared M Baeten, Maribel Acevedo-Quiñones, Allison L Agwu

Journal: The New England journal of medicine 2025;392(13):1261-1276

PMID: 39602624

Full Text on Atypon View on PubMed

Abstract

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.).

Address: Hope Clinic of Emory University School of Medicine, Decatur, GA.; Grady Health System, Atlanta.; Centro Ararat, San Juan, Puerto Rico.; Divisions of Pediatric and Adult Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore.; HIV Netherlands Australia Thailand Research Collaboration, Thai Red Cross AIDS Research Centre and Center of Excellence in Tuberculosis, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.; Be Well Medical Center, Berkley, MI.; Department of Medicine, University of California San Diego, San Diego.; Central Texas Clinical Research, Austin, TX.; Complexo Hospitalar Universitário Professor Edgard Santos, Salvador, Brazil.; Fundación Huésped, Buenos Aires.; Division of Infectious Diseases, Emory University-Ponce de Leon Center Clinical Research Site, HIV/AIDS Clinical Trials Unit, Atlanta.; Department of Medicine, University of California, Los Angeles.; Department of Infectious Diseases, Louisiana State University Health Sciences Center-New Orleans, New Orleans.; Howard Brown Health, Chicago.; Crofoot MD Clinic and Research Center, Houston.; Universidade Federal de São Paulo, São Paulo.; Division of Infectious Diseases, University of Miami Miller School of Medicine, Miami.; Centro de Investigaciones Tecnológicas, Biomédicas y Medioambientales, Universidad Nacional Mayor de San Marcos, Lima, Peru.; Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, TN.; Fundação Oswaldo Cruz-Instituto Nacional de Infectologia Evandro Chagas, Rio de Janeiro.; Optimus Medical Group/StudyOps, San Francisco.; Asociación Civil Selva Amazónica, Iquitos, Peru.; Washington Health Institute, Washington, DC.; Desmond Tutu Health Foundation, Cape Town, South Africa.; Fundação de Medicina Tropical Doutor Heitor Vieira Dourado, Manaus, Brazil.; Therafirst Medical Center, Fort Lauderdale, FL.; Hospital General de Agudos José María Ramos Mejía, Buenos Aires.; Centro de Referência e Treinamento DST/AIDS-SP, São Paulo.; Fenway Health Medical Clinic, Boston.; Mills Clinical Research, West Hollywood, CA.; Philadelphia FIGHT Community Health Centers-Jonathan Lax Treatment Center, Philadelphia.; Wits Reproductive Health and HIV Institute, Faculty of Health Sciences, School of Public Health, University of the Witwatersrand, Johannesburg.; Division of Infectious Diseases, University of Illinois Health Sciences, Chicago.; Centro de Investigacion Farmaceutica Especializada de Occidente, Guadalajara, Mexico.; Institute of HIV Research and Innovation-Pribta Tangerine Clinic, Bangkok, Thailand.; Midway Immunology and Research Center, Fort Pierce, FL.; Ruane Clinical Research, Los Angeles.; Infectious Diseases Service, Hospital Nossa Senhora da Conceição, Porto Alegre, Brazil.; Bios Clinical Research, Palm Springs, CA.; CAN Community Health, Sarasota, FL.; Drew Center for AIDS Research, Education, and Services, Charles R. Drew University, Los Angeles.; Department of Medicine, Division of Infectious Diseases, University of Alabama at Birmingham, Birmingham.; Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo.; Via Libre, Lima, Peru.; Aurum Institute-Pretoria Clinical Research Site, Pretoria, South Africa.; Gilead Sciences, Foster City, CA.; Gilead Sciences, Cambridge, United Kingdom.; Section of Infectious Diseases, Yale School of Medicine, New Haven, CT.

DOI: 10.1056/NEJMoa2411858

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MeSH Terms: Adult, Female, Humans, Male, Middle Aged, Young Adult, Administration, Oral, Anti-HIV Agents, Double-Blind Method, Drug Administration Schedule, HIV Infections, Incidence, Intention to Treat Analysis, Pre-Exposure Prophylaxis, Tenofovir, Transgender Persons, Injections, Subcutaneous, Injection Site Reaction, Emtricitabine, Drug Combinations, Adolescent, Aged, Treatment Outcome, Acetamides, Indazoles