Share

Weight gain in children and adolescents on dolutegravir vs standard of care in the ODYSSEY trial

Title
Weight gain in children and adolescents on dolutegravir vs standard of care in the ODYSSEY trial
Presenter
Anna Turkova
Authors
A. Turkova * (1), C. Kityo (2), H.A Mujuru (3), E. Variava (4), A. Kekitiinwa (5), A. Lugemwa (6), L. Barlow-Mosha (7), C. Ngampiyaskul (8), P. Zuidewind (7), T. Puthanakit (9), R. Mngqbisa (10), N.O. Behuhuma (11), H. Kataike (7), G. Musoro (3), A. Nandudu (2), P. Amuge (5), S. Makumbi (6), S. Danaviah (11), S. Ali (1), B. Wynne (1), Y. Riault (12), S. Welch (13), T.R Cressey (14), A. Violari (4), A. Compagnucci (12), J. Hakim (3), P. Rojo (15), C. Giaquinto (16), D.M Gibb (1), D. Ford (1), the ODYSSEY trial team
Institutions
(1) MRC Clinical Trials Unit at UCL, Institute of Clinical Trials & Methodology, London, United Kingdom, (2) Joint Clinical Research Centre (JCRC), Kampala, Uganda, (3) University of Zimbabwe, Harare, Zimbabwe, (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), Mbarara, Uganda, (7) Makerere University-Johns Hopkins University (MU-JHU) Research Collaboration, Kampala, Uganda, (8) Prapokklao Hospital, Chanthaburi Province, Thailand, (9) HIVNAT, Thai Red Cross AIDS Research Center, Bangkok, Thailand, (10) Enhancing Care Foundation, King Edward VIII Hospital, Durban, South Africa, (11) Africa Health Research Institute (AHRI), Kwazulu-Natal, South Africa, (12) INSERM/ANRS SC10-US19, Essais Thérapeutiques et Maladies Infectieuses, Villejuif, France, (13) University Hospitals Birmingham, Department of Paediatrics, Heartlands Hospital, Birmingham, United Kingdom, (14) PHPT/IRD Research Unit, Faculty of Associated Medical Sciences, Chiang Mai, Thailand, (15) Hospital 12 de Octubre, Universidad Complutense, Department of Pediatrics, Madrid, Spain, (16) University of Padova, Department of Women and Child Health, Padova, Italy

BACKGROUND: Dolutegravir is associated with excessive weight gain in adults. We present the first randomised data in children and adolescents.
METHODS: ODYSSEY is a randomised multi-country trial evaluating dolutegravir + 2NRTIs (DTG) versus standard-of-care (SOC) in children starting first-line or second-line ART. We compared weight, height and BMI-for-age Z-scores (BAZ) between treatment arms using normal regression models adjusting for first-/second-line, randomisation stratification factors and baseline measurements. Proportions becoming newly overweight (BAZ>1-'¤2) or newly obese (BAZ>2) are described.
RESULTS: 707 children were randomised (sub Saharan Africa 88%, Thailand 9%, Europe 4%); 311 started first-line (80% ABC/3TC, 19% TDF/3TC(FTC); 92% efavirenz-based in SOC); 396 second-line (54% ABC/3TC, 26% TDF/3TC(FTC); 72% lopinavir/ritonavir in SOC); 49% were female. At baseline, median age (IQR; range) was 12.2 (9.1, 14.9; 2.9-18.0) years; weight (IQR) 31 (23, 43) kg, height 138 (125, 153) cm, BMI 16.3 (14.9, 18.5) kg/m2, BAZ -0.6 (-1.4, 0.1); 11% had WHO-defined severe thinness/thinness, 5% were overweight, 1% obese; 50% were pubertal/postpubertal. Median follow-up was 142 (124, 159) weeks.
Weight, height and BAZ increased more in DTG than SOC with adjusted difference in means (DTG-SOC) at 96 weeks of 1kg (95%CI 0.3, 1.7; p=0.004), 0.8cm (95%CI 0.2, 1.4; p=0.007) and 0.14 Z-score (95%CI 0.02, 0.26; p=0.018) respectively. Differences between groups emerged early and stabilised (Figure).Treatment differences at 96 weeks in BAZ were similar in males and females (heterogeneity p=0.42), children aged <12 and '¥12 years (p=0.95), prepubertal and pubertal/postpubertal participants (p=0.54), participants starting first- and second-line ART (p=0.746), and those starting TDF vs not(p=0.61). Findings were similar for weight, height and BMI.
Overall, 14 (4%) children/adolescents in DTG and 9 (3%) in SOC were newly overweight or obese at 96 weeks (p=0.29).
CONCLUSIONS: Children grew better after starting DTG. Differences between arms in weight, height and BMI were small and stabilized before 2 years, with few becoming newly overweight or obese in either arm. DTG-based ART was not associated with excessive weight gain in children and adolescents.