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

Authors

Colleen F. Kelley, Emory University, Atlanta, Georgia
Maribel Acevedo-Quiñones, Centro Ararat, San Juan, Puerto Rico
Allison L. Agwu, Johns Hopkins University School of Medicine, Baltimore, MD
Anchalee Avihingsanon, Chulalongkorn University, Bangkok, Thailand
Paul Benson, Be Well Medical Center, Berkley, MI
Jill Blumenthal, University of California, San Diego, San Diego, CA
Cynthia Brinson, Central Texas Clinical Research, Austin, TX
Carlos Brites, Complexo Hospitalar Universitário Professor Edgard Santos, Salvador, Brazil
Pedro Cahn, Fundación Huésped, Buenos Aires, Argentina
Valeria D. Cantos, HIV/AIDS Clinical Trials Unit, Atlanta, GA
Jesse Clark, University of California, Los Angeles, CA
Meredith Clement, LSU Health Sciences Center - New OrleansFollow
Cathy Creticos, Howard Brown Health, Chicago, IL
Gordon Crofoot, Crofoot MD Clinic and Research Center, Houston, TX
Ricardo S. Diaz, Universidade Federal de São Paulo, São Paulo, Brazil
Susanne Doblecki-Lewis, University of Miami Miller School of Medicine, Miami, FL
Jorge A. Gallardo-Cartagena, Universidad Nacional Mayor de San Marcos, Lima, Peru
Aditya Gaur, St. Jude Children's Research Hospital, Memphis, TN
Beatriz Grinsztejn, Fundação Oswaldo Cruz-Instituto Nacional de Infectologia Evandro Chagas, Rio de Janeiro, Brazil
Shawn Hassler, Optimus Medical Group/StudyOps, San Francisco, CA
Juan Carlos Hinojosa, Asociación Civil Selva Amazónica, Iquitos, Peru
Theo Hodge, Washington Health Institute, Washington, DC
Richard Kaplan, Desmond Tutu Health Foundation, Cape Town, South Africa
Marcus Lacerda, Fundação de Medicina Tropical Doutor Heitor Vieira Dourado, Manaus, Brazil
Anthony LaMarca, Therafirst Medical Center, Fort Lauderdale, FL
Marcelo H. Losso, Hospital General de Agudos José María Ramos Mejía, Buenos Aires, Argentina
José Valdez Madruga, Centro de Referência e Treinamento DST/AIDS-SP, São Paulo, Brazil
Kenneth H. Mayer, Fenway Health Medical Clinic, Boston, MA
Anthony Mills, Mills Clinical Research, West Hollywood, CA
et al

Document Type

Article

Publication Date

11-27-2024

Publication Title

The New England Journal of Medicine

Abstract

BACKGROUND: Twice-yearly subcutaneous lenacapavir has been shown to be efficacious for prevention of 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.).

PubMed ID

39602624

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