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


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.