Authors: Mujuru H , Lugemwa A, Puthanakit T, Amuge P, Kityo C, Compagnucci A, Variava E, Kekitiinwa A, Musiime V, BarlowMosha L, Ngampiyaskul C, Zuidewind P, Tumusiime J, Mngqbisa R, Kaudha E, Behuhuma N, Kataike H, Musoro G, Nandudu A, Bwakura M, Ahimbisibwe G, Ounchanum P, Mulindwa A, Nazzinda R, Ssenyonga M, Kanjanavanit S, Nathoo K, Makumbi S, Danaviah S, Nakabuye S, Chalermpantmetagul S, Rutebarika D, Nalusiba S, Srirompotong U, Ali S, Wynne B, Riault Y, Welch S, Cressey T, Violari A, Giaquinto C, Rojo P, Gibb D, Ford D, Turkova A
Published in: IAS 2021 and International Workshop on HIV Pediatrics 2021
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 (DTG) + 2NRTIs versus standard-of-care (SOC) in children starting first 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. Early differences between groups stabilised. 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 other (p=0.61). Findings were similar for weight and height. 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. Small differences between arms in weight, height and BMI stabilized before 2 years, with few becoming newly overweight/ obese in either arm. DTG-based ART was not associated with excessive weight gain in children and adolescents.