Authors: P Amuge on behalf of the ODYSSEY trial team
Published in: International workshop on HIV pediatrics 2021
Background: ODYSSEY, a multi-country randomised trial, demonstrated superior treatment efficacy for dolutegravir (DTG) plus two NRTIs versus standard-ofcare (SOC) in 707 children ≥14kg (median age 12 years) starting first- or second-line ART. We report results for an additional cohort of 85 children <14kg, who completed 96 weeks follow-up on 28th June 2021.
Methods: The primary outcome is a Kaplan-Meier (KM) estimated proportion of treatment failure defined as confirmed viral load (VL) ≥400c/mL after week 36, lack of virological response by 24 weeks with ART switch for failure, death, or new/recurrent WHO 4 or severe WHO 3 event by 96 weeks. Bayesian estimation was pre-specified as the primary analysis of participants <14kg, incorporating evidence obtained from the ≥14kg participants as a prior distribution, with relative weight 78%, based on clinical opinion elicited before availability of results for children ≥14kg. Results: 85 children <14kg were randomised (Uganda 43, Zimbabwe 22, South Africa 20); 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 and 22 were 10-<14kg. 72 children started first-line (29/37 PI-based among SOC); 13 second-line (3/6 PI-, 2 raltegravir- and 1 nevirapine-based among SOC). Median (IQR) followup was 120 (97-132) weeks; 5 (6%) children were lost to follow-up. 11 children in the DTG arm had treatment failure by 96 weeks (K-M estimated proportion 28%) vs 21 (48%) SOC; 8 vs. 16 failures were virological. 8 (25%) DTG vs 17 (46%) SOC failed on first line; 3 (48%) vs 4 (60%) failed on second-line. The Bayesian estimated difference in treatment failure (DTG-SOC) in participants <14kg was -11% (95% CI -19%, -2%; P=0.02). A standalone analysis of the <14kg cohort provided an estimated difference in treatment failure of -20% (95% CI -38%, -1%; P=0.04). At 96 weeks, 77% of children in the DTG arm had VL<50c/mL compared with 50% in SOC (P=0.02); corresponding proportions with VL<400c/mL were 91% vs. 71% (P=0.03). There were 15 SAEs (11 children) in the DTG arm versus 19 (11 children) in SOC (P=0.92, comparing children), including 2 versus 4 deaths; 36 (19 children) had grade ≥3 adverse events in DTG vs 34 (21 children) in SOC (p=0.79). In the DTG arm, 41/42 children remained on DTG at last visit, with no changes to NRTI backbone; 1 child in DTG stopped ART 3 weeks post enrolment and withdrew 2 weeks later. In the SOC arm, 37/43 children remained on their initial treatment regimen at last visit; changes included 4 children who switched ART due to treatment failure.
Conclusions: DTG-based ART was superior to SOC (predominantly PI-based) in young children starting first or second-line, judged on treatment failure by 96 weeks. The treatment benefit for DTG in the <14kg cohort was consistent with that observed in children enrolled ≥14kg. There were no safety concerns on DTG. These results strongly support WHO guidelines recommending DTG-based regimens for young children and provide impetus for rapid procurement of dispersible dolutegravir.