Neuropsychiatric manifestations and sleep disturbances with dolutegravir-based antiretroviral therapy versus standard of care in children and adolescents: a secondary analysis of the ODYSSEY trial.

Autor:	Turkova A; Medical Research Council Clinical Trials Unit at University College London, London, UK. Electronic address: a.turkova@ucl.ac.uk., White E; Medical Research Council Clinical Trials Unit at University College London, London, UK., Kekitiinwa AR; Baylor College of Medicine, Kampala, Uganda., Mumbiro V; University of Zimbabwe Clinical Research Centre, Harare, Zimbabwe., Kaudha E; Joint Clinical Research Centre, Kampala, Uganda., Liberty A; Perinatal HIV Research Unit, University of the Witwarsrand, Johannesburg, South Africa., Ahimbisibwe GM; Makerere University-Johns Hopkins University Research Collaboration, Kampala, Uganda., Moloantoa T; Perinatal HIV Research Unit, University of the Witwarsrand, Johannesburg, South Africa., Srirompotong U; Pediatric Department, Khon Kaen Hospital, Thailand., Mosia NR; Department of Paediatrics and Children Health, King Edward VIII Hospital, Enhancing Care Foundation, University of KwaZulu-Natal, Durban, South Africa., Puthanakit T; HIVNAT, Thai Red Cross AIDS Research Center, Bangkok, Thailand; Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, Thailand., Kobbe R; Institute for Infection Research and Vaccine Development, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany; Department of Infectious Disease Epidemiology, Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany., Fortuny C; Infectious Diseases Department, Institut de Recerca Sant Joan de Déu, Sant Joan de Déu Children's Hospital, Barcelona, Spain; Department of Surgery and Medico-Surgical Specialties, Faculty of Medicine and Health Sciences, Universitat de Barcelona, Barcelona, Spain., Kataike H; Makerere University-Johns Hopkins University Research Collaboration, Kampala, Uganda., Bbuye D; Baylor College of Medicine, Kampala, Uganda., Na-Rajsima S; Pediatric Department, Mahasarakam Hospital, Thailand., Coelho A; INSERM/ANRS SC10-US19, Essais Thérapeutiques et Maladies Infectieuses, Villejuif, France., Lugemwa A; Joint Clinical Research Centre, Mbarara, Uganda., Bwakura-Dangarembizi MF; University of Zimbabwe Clinical Research Centre, Harare, Zimbabwe., Klein N; Infection, Immunity & Inflammation Department, UCL Great Ormond Street Institute of Child Health, London, UK; Africa Health Research Institute, Kwazulu-Natal, South Africa., Mujuru HA; University of Zimbabwe Clinical Research Centre, Harare, Zimbabwe., Kityo C; Joint Clinical Research Centre, Kampala, Uganda., Cotton MF; Children's Infectious Diseases Clinical Research Unit, Family Center for Research with Ubuntu, Department of Paediatrics and Child Health, University of Stellenbosch, Cape Town, South Africa., Ferrand RA; Department of Clinical Research, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, UK., Giaquinto C; Department of Women and Child Health, Padova, University of Padova, Italy., Rojo P; Pediatric Infectious Diseases Unit, Hospital 12 de Octubre, Madrid, Spain., Violari A; Perinatal HIV Research Unit, University of the Witwarsrand, Johannesburg, South Africa., Gibb DM; Medical Research Council Clinical Trials Unit at University College London, London, UK., Ford D; Medical Research Council Clinical Trials Unit at University College London, London, UK.
Jazyk:	angličtina
Zdroj:	The Lancet. Child & adolescent health [Lancet Child Adolesc Health] 2023 Oct; Vol. 7 (10), pp. 718-727. Date of Electronic Publication: 2023 Aug 08.
DOI:	10.1016/S2352-4642(23)00164-5
Abstrakt:	Background: Cohort studies in adults with HIV showed that dolutegravir was associated with neuropsychiatric adverse events and sleep problems, yet data are scarce in children and adolescents. We aimed to evaluate neuropsychiatric manifestations in children and adolescents treated with dolutegravir-based treatment versus alternative antiretroviral therapy. Methods: This is a secondary analysis of ODYSSEY, an open-label, multicentre, randomised, non-inferiority trial, in which adolescents and children initiating first-line or second-line antiretroviral therapy were randomly assigned 1:1 to dolutegravir-based treatment or standard-of-care treatment. We assessed neuropsychiatric adverse events (reported by clinicians) and responses to the mood and sleep questionnaires (reported by the participant or their carer) in both groups. We compared the proportions of patients with neuropsychiatric adverse events (neurological, psychiatric, and total), time to first neuropsychiatric adverse event, and participant-reported responses to questionnaires capturing issues with mood, suicidal thoughts, and sleep problems. Findings: Between Sept 20, 2016, and June 22, 2018, 707 participants were enrolled, of whom 345 (49%) were female and 362 (51%) were male, and 623 (88%) were Black-African. Of 707 participants, 350 (50%) were randomly assigned to dolutegravir-based antiretroviral therapy and 357 (50%) to non-dolutegravir-based standard-of-care. 311 (44%) of 707 participants started first-line antiretroviral therapy (ODYSSEY-A; 145 [92%] of 157 participants had efavirenz-based therapy in the standard-of-care group), and 396 (56%) of 707 started second-line therapy (ODYSSEY-B; 195 [98%] of 200 had protease inhibitor-based therapy in the standard-of-care group). During follow-up (median 142 weeks, IQR 124-159), 23 participants had 31 neuropsychiatric adverse events (15 in the dolutegravir group and eight in the standard-of-care group; difference in proportion of participants with ≥1 event p=0·13). 11 participants had one or more neurological events (six and five; p=0·74) and 14 participants had one or more psychiatric events (ten and four; p=0·097). Among 14 participants with psychiatric events, eight participants in the dolutegravir group and four in standard-of-care group had suicidal ideation or behaviour. More participants in the dolutegravir group than the standard-of-care group reported symptoms of self-harm (eight vs one; p=0·025), life not worth living (17 vs five; p=0·0091), or suicidal thoughts (13 vs none; p=0·0006) at one or more follow-up visits. Most reports were transient. There were no differences by treatment group in low mood or feeling sad, problems concentrating, feeling worried or feeling angry or aggressive, sleep problems, or sleep quality. Interpretation: The numbers of neuropsychiatric adverse events and reported neuropsychiatric symptoms were low. However, numerically more participants had psychiatric events and reported suicidality ideation in the dolutegravir group than the standard-of-care group. These differences should be interpreted with caution in an open-label trial. Clinicians and policy makers should consider including suicidality screening of children or adolescents receiving dolutegravir. Funding: Penta Foundation, ViiV Healthcare, and UK Medical Research Council. Competing Interests: Declaration of interests AT reports receiving funding for their service on the ViiV Healthcare advisory board with the payment made to their respective employer. All other authors declare no competing interests. (Copyright © 2023 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)
Databáze:	MEDLINE
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