• Anna Turkova, Ellen White, Hilda A Mujuru, Adeodata R Kekitiinwa, Cissy M Kityo, Avy Violari, Abbas Lugemwa, Tim R Cressey, Philippa Musoke, Ebrahim Variava, Mark F Cotton, Moherndran Archary, Thanyawee Puthanakit, Osee Behuhuma, Robin Kobbe, Steven B Welch, Mutsa Bwakura-Dangarembizi, Pauline Amuge, Elizabeth Kaudha, Linda Barlow-Mosha, Shafic Makumbi, Nastassja Ramsagar, Chaiwat Ngampiyaskul, Godfrey Musoro, Lorna Atwine, Afaaf Liberty, Victor Musiime, Dickson Bbuye, Grace M Ahimbisibwe, Suwalai Chalermpantmetagul, Shabinah Ali, Tatiana Sarfati, Ben Wynne, Clare Shakeshaft, Angela Colbers, Nigel Klein, Sarah Bernays, Yacine Saïdi, Alexandra Coelho, Tiziana Grossele, Alexandra Compagnucci, Carlo Giaquinto, Pablo Rojo, Deborah Ford, Diana M Gibb, and ODYSSEY Trial Team.
• From the Medical Research Council Clinical Trials Unit at University College London, Institute of Clinical Trials and Methodology (A.T., E.W., S.A., T.S., B.W., C.S., D.F., D.M.G.), the University College London Great Ormond Street Institute of Child Health (N.K.), and the Department of Global Health and Development, London School of Hygiene and Tropical Medicine (S.B.), London, and Heartlands Hospital, University Hospitals Birmingham NHS Foundation Trust, Birmingham (S.B.W.) - all in the United Kingdom; the University of Zimbabwe, Harare (H.A.M., M.B.-D., G.M.); Baylor College of Medicine, Fort Portal (A.R.K., P.A., D.B.), the Joint Clinical Research Center, Mbarara (A. Lugemwa, S.M., L.A.), and the Joint Clinical Research Center (C.M.K., E.K., V.M.), Makerere University-Johns Hopkins University Research Collaboration (P.M., L.B.-M., G.M.A.), and Makerere University (V.M.), Kampala - all in Uganda; the Perinatal HIV Research Unit, University of the Witwatersrand, Johannesburg (A.V., N.R., E.V., A. Liberty), the Family Centre for Research with Ubuntu, the Department of Paediatrics and Child Health, Stellenbosch University, Tygerberg (M.F.C.), the Department of Paediatrics and Children Health, King Edward VIII Hospital, University of KwaZulu-Natal (M.A.), and the Africa Health Research Institute (O.B., N.K.), Durban - all in South Africa; the Program for HIV Prevention and Treatment-Institut de Recherche pour le Développement Research Unit, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai (T.R.C., S.C.), the Faculty of Medicine, Chulalongkorn University (T.P.), and HIV-NAT (HIV Netherlands Australia Thailand Research Collaboration), Thai Red Cross AIDS Research Center, Bangkok (T.P.), and Prapokklao Hospital, Chanthaburi (C.N.) - all in Thailand; the First Department of Medicine, Division of Infectious Diseases, University Medical Center Hamburg-Eppendorf, Hamburg, Germany (R.K.); the Department of Pharmacy, Radboud Institute for Health Sciences, Radboud University Medical Center, Nijmegen, the Netherlands (A. Colbers); the School of Public Health, University of Sydney, Sydney (S.B.); INSERM-ANRS SC10-US019, Essais Thérapeutiques et Maladies Infectieuses, Villejuif, France (Y.S., A. Coelho, A. Compagnucci); the Penta Foundation (T.G., C.G.), and the Department of Women and Child Health, University of Padua (C.G.) - both in Padua, Italy; and the Pediatric Infectious Diseases Unit, Hospital Universitario 12 de Octubre, Madrid (P.R.).
• N. Engl. J. Med. 2021 Dec 30; 385 (27): 253125432531-2543.

BackgroundChildren with human immunodeficiency virus type 1 (HIV-1) infection have limited options for effective antiretroviral treatment (ART).MethodsWe conducted an open-label, randomized, noninferiority trial comparing three-drug ART based on the HIV integrase inhibitor dolutegravir with standard care (non-dolutegravir-based ART) in children and adolescents starting first- or second-line ART. The primary end point was the proportion of participants with virologic or clinical treatment failure by 96 weeks, as estimated by the Kaplan-Meier method. Safety was assessed.ResultsFrom September 2016 through June 2018, a total of 707 children and adolescents who weighed at least 14 kg were randomly assigned to receive dolutegravir-based ART (350 participants) or standard care (357). The median age was 12.2 years (range, 2.9 to 18.0), the median weight was 30.7 kg (range, 14.0 to 85.0), and 49% of the participants were girls. By design, 311 participants (44%) started first-line ART (with 92% of those in the standard-care group receiving efavirenz-based ART), and 396 (56%) started second-line ART (with 98% of those in the standard-care group receiving boosted protease inhibitor-based ART). The median follow-up was 142 weeks. By 96 weeks, 47 participants in the dolutegravir group and 75 in the standard-care group had treatment failure (estimated probability, 0.14 vs. 0.22; difference, -0.08; 95% confidence interval, -0.14 to -0.03; P = 0.004). Treatment effects were similar with first- and second-line therapies (P = 0.16 for heterogeneity). A total of 35 participants in the dolutegravir group and 40 in the standard-care group had at least one serious adverse event (P = 0.53), and 73 and 86, respectively, had at least one adverse event of grade 3 or higher (P = 0.24). At least one ART-modifying adverse event occurred in 5 participants in the dolutegravir group and in 17 in the standard-care group (P = 0.01).ConclusionsIn this trial involving children and adolescents with HIV-1 infection who were starting first- or second-line treatment, dolutegravir-based ART was superior to standard care. (Funded by ViiV Healthcare; ODYSSEY ClinicalTrials.gov number, NCT02259127; EUDRACT number, 2014-002632-14; and ISRCTN number, ISRCTN91737921.).Copyright © 2021 Massachusetts Medical Society.

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