Year: 2021
Type: article
Study designs: Randomized Controlled Trial, Clinical Trial
Abstract: BACKGROUND: Safe and effective long-acting injectable agents for preexposure prophylaxis (PrEP) for human immunodeficiency virus (HIV) infection are needed to increase the options for preventing HIV infection. METHODS: We conducted a randomized, double-blind, double-dummy, noninferiority trial to compare long-acting injectable cabotegravir (CAB-LA, an integrase strand-transfer inhibitor [INSTI]) at a dose of 600 mg, given intramuscularly every 8 weeks, with daily oral tenofovir disoproxil fumarate-emtricitabine (TDF-FTC) for the prevention of HIV infection in at-risk cisgender men who have sex with men (MSM) and in at-risk transgender women who have sex with men. Participants were randomly assigned (1:1) to receive one of the two regimens and were followed for 153 weeks. HIV testing and safety evaluations were performed. The primary end point was incident HIV infection. RESULTS: The intention-to-treat population included 4566 participants who underwent randomization; 570 (12.5%) identified as transgender women, and the median age was 26 years (interquartile range, 22 to 32). The trial was stopped early for efficacy on review of the results of the first preplanned interim end-point analysis. Among 1698 participants from the United States, 845 (49.8%) identified as Black. Incident HIV infection occurred in 52 participants: 13 in the cabotegravir group (incidence, 0.41 per 100 person-years) and 39 in the TDF-FTC group (incidence, 1.22 per 100 person-years) (hazard ratio, 0.34; 95% confidence interval, 0.18 to 0.62). The effect was consistent across prespecified subgroups. Injection-site reactions were reported in 81.4% of the participants in the cabotegravir group and in 31.3% of those in the TDF-FTC group. In the participants in whom HIV infection was diagnosed after exposure to CAB-LA, INSTI resistance and delays in the detection of HIV infection were noted. No safety concerns were identified. CONCLUSIONS: CAB-LA was superior to daily oral TDF-FTC in preventing HIV infection among MSM and transgender women. Strategies are needed to prevent INSTI resistance in cases of CAB-LA PrEP failure. (Funded by the National Institute of Allergy and Infectious Diseases and others; HPTN 083 ClinicalTrials.gov number, NCT02720094.).
Source: New England Journal of Medicine
Authors: Raphael J. Landovitz, Deborah Donnell, Meredith E. Clement, Brett Hanscom, Leslie Cottle, Lara Coelho, Robinson Cabello, Suwat Chariyalertsak, Eileen F. Dunne, Ian Frank, Jorge A. Gallardo-Cartagena, Aditya H. Gaur, Pedro Gonzales, Ha V. Tran, Juan C. Hinojosa, Esper G. Kallas, Colleen F. Kelley, Marcelo H. Losso, J. Valdez Madruga, Keren Middelkoop, Nittaya Phanuphak, Breno Santos, Omar Sued, Javier Valencia Huamaní, Edgar T. Overton, Shobha Swaminathan, Carlos del Rio, Roy M. Gulick, Paul Richardson, Philip Sullivan, Estelle Piwowar-Manning, Mark Marzinke, Craig Hendrix, Maoji Li, Zhe Wang, Jeanne Marrazzo, Eric Daar, Aida Asmelash, Todd T. Brown, Peter Anderson, Susan H. Eshleman, Marcus Bryan, Cheryl Blanchette, Jonathan Lucas, Christina Psaros, Steven Safren, Jeremy Sugarman, Hyman Scott, Joseph J. Eron, Sheldon D. Fields, Nirupama D. Sista, Kailazarid Gomez-Feliciano, Andrea Jennings, Ryan M. Kofron, Timothy H. Holtz, Katherine Shin, James F. Rooney, Kimberly Y. Smith, William Spreen, David Margolis, Alex Rinehart, Adeola Adeyeye, Myron S. Cohen, Marybeth McCauley, Beatriz Grinsztejn
Institutions: University of California, Los Angeles, Universidade de São Paulo, Fred Hutch Cancer Center, San Francisco Department of Public Health, Gilead Sciences (United States), Harbor–UCLA Medical Center, Louisiana State University Health Sciences Center New Orleans, Fundação Oswaldo Cruz, Via Libre, Chiang Mai University, Centers for Disease Control and Prevention, Emory University, University of Pennsylvania, National University of San Marcos, St. Jude Children's Research Hospital, Asociación Civil Impacta Salud y Educación, University of North Carolina at Chapel Hill, Hospital Ramos Mejía, CINTESIS.UPT, University of Cape Town, Institute of Infectious Disease and Molecular Medicine, Hospital Nossa Senhora da Conceição, Fundación Huésped, University of Alabama at Birmingham, Rutgers New Jersey Medical School, Weill Cornell Medicine, Johns Hopkins University, Family Health International 360, The Lundquist Institute, University of Colorado Anschutz, Massachusetts General Hospital, University of Miami, Pennsylvania State University, Office of AIDS Research, National Institutes of Health, National Institute of Allergy and Infectious Diseases
Language: English
Subfield: Infectious Diseases
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
Awards: G1050281965, G1214792496, G1310891712, G2127051194, G2548217053, G277532835, G2993261131, G3598573620, G547379174, G793395730, G9000027606, G9000035439, G9000072712, ICAP Clinical Trials Unit, Training for Scientists Conducting Research to Reduce HIV/AIDS Health Disparities, Thailand HIV/AIDS and Infectious Disease Clinical Trials Unit (THAI CTU), HIV/AIDS Clinical Trials Units University of Cape Town CTU 2020 to 2027, G95499620, G95938990
OpenAlex ID: W3190424399