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Title
HPTN083 interim results: Pre-exposure prophylaxis (PrEP) containing long-acting injectable cabotegravir (CAB-LA) is safe and highly effective for cisgender men and transgender women who have sex with men (MSM,TGW)
Presenter
Raphael J. Landovitz
Authors
R.J. Landovitz * (1), D. Donnell (2), M. Clement (3), B. Hanscom (2), L. Cottle (2), L. Coelho (4), R. Cabello (5), S. Chariyalestak (6), E. Dunne (7), I. Frank (8), J. Gallardo (9), A. Gaur (10), P. Gonzalez (11), V. Ha (12), J. Hinojosa (13), E. Kallas (14), C. Kelley (15), M. Losso (16), J. Valdez Madruga (17), K. Middelkoop (18), N. Phanuphak (19), B. Santos (20), O. Sued (21), J. Valencia Huanami (22), E.T. Overton (23), S. Swaminathan (24), C. del Rio (25), R. Gulick (26), P. Richardson (27), P. Sullivan (28), E. Piwowar-Manning (28), M. Marzinke (28), J. Marrazzo (29), E. Daar (30), A. Asmelash (31), P. Anderson (32), S. Eshleman (33), C. Blanchette (31), J. Lucas (31), C. Psaros (34), S. Safren (35), J. Sugarman (36), H. Scott (37), J. Eron (38), S. Fields (39), K. Gomez-Feliciano (31), A. Jennings (31), K. Shin (40), J. Rooney (41), W. Spreen (42), D. Margolis (42), A. Rinehart (42), A. Adeyeye (43), M. Cohen (44), M. McCauley (31), B. Grinsztejn (45), for the HPTN 083 Study Team
Institutions
(1) University of California Los Angeles, UCLA Center for Clinical AIDS Research & Education, Los Angeles, United States, (2) Fred Hutchinson Cancer Institute, Seattle, United States, (3) Louisiana State University, Baton Rouge, United States, (4) Instituto de Pesquisa Clinica Evandro Changas-Fiocruz, Rio de Janeiro, Brazil, (5) Via Libre Clinical Research Center, Lima, Peru, (6) Chiang Mai University, Research Institute for Health Sciences, Chiang Mai, Thailand, (7) Center for Disease Control and Prevention, Silom Clinic Bangkok Thailand, Atlanta, United States, (8) University of Pennsylvania, Philadelphia, United States, (9) CITBM CRS, Lima, Peru, (10) St. Jude Children''s Research Hospital, Memphis, United States, (11) Asociacion Civil Impacta Salud y Educacion, Lima, Peru, (12) Yen Hoa Clinic, Hanoi, Vietnam, (13) Asociación Civil Selva Amazónica, Iquitos, Peru, (14) University of Sao Paulo, Sao Paulo, Brazil, (15) Emory University School of Medicine, Atlanta, United States, (16) Hospital General de Agudos JM Ramos Mejia, Buenos Aires, Argentina, (17) Sao Paulo DST/AIDS CRS, Sao Paulo, Brazil, (18) Groote Schuur Hospital, Cape Town, South Africa, (19) Thai Red Cross AIDS Research Centre, Bangkok, Thailand, (20) Hospital Nossa Senhora da Conceição, Porto Alegre, Brazil, (21) Fundación Huésped, Buenos Aires, Argentina, (22) Barranco CRS, Lima, Peru, (23) University of Alabama at Birmingham, Birmingham, United States, (24) Rutgers New Jersey Medical School, Newark, United States, (25) Emory University Rollins School of Public Health, Atlanta, United States, (26) Cornell University Weill Medical College, Division of Infectious Diseases, New York, United States, (27) Johns Hopkins University, Department of Pathology, Baltimore, United States, (28) Johns Hopkins University, Baltimore, United States, (29) University of Alabama at Birmingham School of Medicine, Birmingham, United States, (30) Lundquist Institute, Harbor-UCLA Medical Center, Los Angeles, United States, (31) FHI 360, Washington, United States, (32) University of Colorado Anschutz Campus, Aurora, United States, (33) Johns Hopkins University School of Medicine, Baltimore, United States, (34) Massachusetts General Hospital, Boston, United States, (35) University of Miami, Miami, United States, (36) Johns Hopkins Berman Institute of Bioethics, Baltimore, United States, (37) San Francisco Department of Public Health, San Francisco, United States, (38) University of North Carolina at Chapel Hill, Division of Infectious Diseases, Chapel Hill, United States, (39) New York Institute of Technology, Old Westbury, United States, (40) Division of AIDS, Pharmaceutical Affairs Branch, Rockville, United States, (41) Gilead Sciences, Foster City, United States, (42) ViiV Healthcare, Durham, United States, (43) Division of AIDS, NIAID, NIH, Clinical Prevention Research Branch, Rockville, United States, (44) University of North Carolina School of Medicine, Department of Medicine, Chapel Hill, United States, (45) Instituto de Pesquisa Clinica Evandro Chagas-Fiocruz, Rio de Janeiro, Brazil

BACKGROUND: HPTN 083 is a Phase 2b/3 randomized multicenter double-blind, double-dummy, clinical trial evaluating safety and efficacy of long-acting injectable cabotegravir (CAB) compared to daily oral TDF/FTC for HIV PrEP. The blinded trial was stopped at a pre-planned interim DSMB review in May 2020.
METHODS: HIV-uninfected MSM and TGW at increased HIV risk were randomized 1:1 to either active CAB +TDF/FTC placebo (oral cabotegravir(CAB) for 5 weeks, then IM injections every 8 weeks for 148 weeks) or active TDF/FTC+CAB placebo (oral placebo for 5 weeks, then placebo injections on the same schedule). All participants were offered daily oral TDF/FTC for 48 weeks after last injection. The primary endpoints were incident HIV infection and grade 2 or higher clinical and laboratory events.
RESULTS: Participants were enrolled at 43 sites in Africa, Asia, Latin America, and the US (N=4566); median age: 26y (IQR 22-32); 12%TGW (n=567); 50% of US participants were Black (n=844). Participant retention at 6, 12, and 24 months was 91%, 87%, and 74%, respectively. Fifty-two incident HIV infections were observed over 6385 person-years, with overall HIV incidence 0.81% (95%CI 0.61-1.07); 39 infections were in the TDF/FTC arm (incidence 1.22%, 95%CI 0.87-1.67); 13 infections were in the CAB arm (incidence 0.41%, 95%CI 0.22-0.69%); HR: 0.34 (95%CI 0.18-0.62). Blinded study product injections covered 92% of person-years. Adherence to oral TDF/FTC was high; in a random subset of 372 TDF/FTC participants 87% had plasma samples with detectable concentrations, and 75% had concentrations consistent with daily dosing. CAB and TDF/FTC were both well tolerated; most adverse events were mild/moderate and balanced between arms. Injection site reactions, pyrexia, and hypertension were significantly more common in CAB participants, nausea was significantly more common in TDF/FTC participants. Injection intolerance led to discontinuation in 46 (2.2%) active CAB-LA recipients and was associated with the severity of the intolerance/reaction.
CONCLUSIONS: CAB and TDF/FTC were both safe and highly effective for PrEP in HPTN083, with estimated HIV incidence in the CAB arm 66% lower than in the TDF/FTC arm. CAB is the first injectable agent proven effective for HIV PrEP; a companion trial in cisgender women is ongoing.