Dolutegravir as First- or Second-line Treatment for Children With HIV: 240-Week Follow-up of the ODYSSEY Randomized Trial.

Background: The World Health Organization recommends dolutegravir (DTG) as the anchor antiretroviral therapy (ART) drug for children with HIV. Methods: The ODYSSEY randomized trial evaluated DTG-based ART vs non-DTG standard of care (SOC) over 96 weeks in children starting first-line ART or switching to second-line. Participant follow-up was extended to 240 weeks; ART in extended follow-up was per national guidelines. Flexible parametric survival models estimated the proportion of participants with treatment failure on randomized allocation, accounting for treatment switches through censoring and inverse probability of censoring weights. Adverse events were analyzed in the intention-to-treat population. Results: ODYSSEY enrolled 792 participants (392 DTG, 400 SOC): 311 started first-line (SOC, 92% efavirenz) and 396 second-line (SOC, 98% ritonavir-boosted protease inhibitors). The median (range) age at enrollment was 11.4 years (0.1-18.0); weight was 28.7 kg (3.4-85.0); and 89% were from Africa. Median follow-up on randomized allocation was 286 weeks (IQR, 230-310) for DTG and 204 weeks (168-240) for SOC. Among SOC participants, 23% switched to DTG before 192 weeks, 65% before 240 weeks. By 240 weeks, 74 participants on DTG and 131 on SOC had treatment failure (estimated, 19% vs 34%; difference [DTG-SOC], -15%; 95% CI, -21% to -9%; Conclusions: DTG showed superior efficacy vs SOC over 240 weeks in children, with no safety concerns.