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


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.