Dolutegravir as first- or second-line treatment for children living with HIV: 240-week follow-up of the ODYSSEY randomised trial

Abstract

Abstract Background The World Health Organization recommends dolutegravir (DTG) as the anchor antiretroviral therapy (ART) drug for children living with HIV. Methods The ODYSSEY randomised trial evaluated DTG-based ART versus non-DTG standard-of-care (SOC) over 96 weeks in children starting first-line or switching to second-line ART. 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 randomised allocation, accounting for treatment-switches through censoring and inverse-probability-of-censoring-weights. Adverse events were analysed 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). Median (range) age at enrolment was 11.4 years (0.1-18.0), weight was 28.7 kg (3.4-85.0); 89% were from Africa. Median follow-up on randomised allocation was 286 weeks (IQR 230-310) on DTG and 204 weeks (168-240) on SOC. 23% of SOC participants 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; P<0.001). Treatment effects were similar on first- and second-line (P=0.10). Proportions of participants with serious adverse events (52 DTG vs 53 SOC; P=0.92) or grade ≥3 adverse events (98 DTG vs 121 SOC; P=0.09) were similar by arm over 192 weeks. Conclusions DTG showed superior efficacy versus SOC over 240 weeks in children, with no safety concerns.