Share

A randomised comparison of DTG-based ART vs standard of care in infants and young children living with HIV weighing 3 to 14kg: results from the ODYSSEY trial

Title
A randomised comparison of DTG-based ART vs standard of care in infants and young children living with HIV weighing 3 to 14kg: results from the ODYSSEY trial
Presenter
Abbas Lugemwa
Authors
A. Lugemwa * (1), H. Mujuru (2), B. Wynne (3), A. Violari (4), A. Kekitiinwa (5), C. Kityo (6), M. Archary (7), E. Variava (8), T. Sarfati (3), C. Shakeshaft (3), R. Turner (3), K. Nathoo (2), E. Chidziva (2), L. Atwine (1), N. Ramsagar (4), A. Liberty (4), P. Amuge (5), E. Kaudha (6), A. Nanduudu (6), R. Mngqibisa (7), R. Mosia (7), M. Cotton (9), T. Cressey (10), T. Puthanakit (11), A. Compagnucci (12), C. Giaquinto (13), P. Rojo (14), D. Ford (3), D.M Gibb (3), A. Turkova (3), ODYSSEY trial team
Institutions
(1) Joint Clinical Research Centre (JCRC), Mbarara, Uganda, (2) University of Zimbabwe, Harare, Zimbabwe, (3) MRC Clinical Trials Unit at UCL, Institute of Clinical Trials & Methodology, London, United Kingdom, (4) Perinatal HIV Research Unit, University of the Witwarsrand, Johannesburg, South Africa, (5) Baylor College of Medicine, Kampala, Uganda, (6) Joint Clinical Research Centre (JCRC), Kampala, Uganda, (7) Enhancing Care Foundation: King Edward VIII Hospital, Department of Women and Child Health, Durban, South Africa, (8) Klerksdorp Tshepong Hospital Complex, Matlosana, South Africa, (9) Family Center for Research with Ubuntu, Department of Paediatrics & Child Health, Stellenbosch University, Tygerberg, South Africa, (10) PHPT/IRD Research Unit, Faculty of Associated Medical Sciences, Chiang Mai, Thailand, (11) HIVNAT, Thai Red Cross AIDS Research Center, Bangkok, Thailand, (12) INSERM/ANRS SC10-US19, Essais Thérapeutiques et Maladies Infectieuses, Villejuif, France, (13) University of Padova, Department of Women and Child Health, Padova, Italy, (14) Hospital 12 de Octubre, Universidad Complutense, Department of Pediatrics, Madrid, Spain

BACKGROUND: Children living with HIV are rapidly transitioning to DTG-based ART. Children '¥20kg can use 50mg DTG adult tablets; global rollout for those <20kg will require dispersible DTG, which will become available from generic manufacturers in low and middle-income countries later in 2021. ODYSSEY, a multi-country randomised trial, demonstrated superior treatment efficacy for dolutegravir (DTG) plus two NRTIs versus standard-of-care (SOC) in 707 children and adolescents enrolled weighing '¥14kg (median age 12 years; 96% '¥6 years) starting first- and second-line ART. We will report results for an additional 85 children weighing <14kg randomised to DTG-based ART (5mg DTG dispersible tablets dosed using WHO weightbands) versus SOC.
METHODS: The primary outcome is a Kaplan-Meier estimated proportion of treatment failure defined as confirmed viral load(VL) '¥400c/mL after week 36, lack of virological response by 24 weeks followed by ART switch, death or new/recurrent WHO4/severe WHO3 event by 96 weeks.
RESULTS: 85 children <14kg were randomised (Uganda 43, Zimbabwe 22, South Africa 20) between July 2018'August 2019; 42 to DTG and 43 to SOC. Median(range) age was 1.4 years (0.1-5.9); 23 were 3-<6kg, 40 were 6-<10kg, 22 were 10-<14kg; 34% were WHO stage 3/4; median(IQR) CD4% was 23(16-31). 72 children started first-line and 13 second-line. First-line SOC participants started lopinavir/ritonavir (29), efavirenz (4) or nevirapine (4); second-line SOC participants started lopinavir/ritonavir (3), raltegravir (2) or nevirapine (1). NRTI-backbones in both groups were predominantly ABC/3TC for first-line and ZDV/3TC for second-line. On 28 June 2021, all children will have completed 96 weeks follow-up. Results will include the estimated difference in risk of treatment failure by 96 weeks between treatment groups using a Bayesian approach, incorporating evidence from the main ODYSSEY trial of children '¥14kg as an informative prior, and the estimated difference in risk of treatment failure using data only from children <14kg. Cross-sectional VLs and safety outcomes will be compared between groups and treatment changes will be described.
CONCLUSIONS: ODYSSEY will provide the first randomised evidence for DTG in infants and young children <14kg; these results are keenly anticipated to support World Health Organization guidelines recommending DTG-based regimens down to 4 weeks of age and 3kg.