Background:
ODYSSEY demonstrated superior 96-week efficacy for dolutegravir(DTG)+2NRTIs versus standard-of-care (SOC, 77% efavirenz first-line, 96% boosted PI second-line) in children starting first-line (ODYSSEY A) or second-line ART (ODYSSEY B). During a further ~3 years’ extended follow-up in Africa and Thailand, children on SOC were switching to DTG following national guidelines. Here we present efficacy and safety of DTG compared to SOC over 192 weeks and virological suppression in SOC participants post-switch to DTG.
Methods:
The proportion of children with treatment failure (confirmed viral load (VL) ≥400c/mL after week 36, lack of virological response by week-24 with ART switch, death or new/recurrent WHO4/severe WHO3 event) was compared between trial arms by intention-to-treat using Kaplan-Meier. Viral suppression in SOC participants was defined as VL<400c/mL in the most recent sample within 24 weeks pre-DTG switch and 48 weeks post-switch.
Results:
792 children were randomised (392 DTG,400 SOC); median(range) age 11.4(0.1-18) years, and weight 29(3.4-85)kg. 383 children started first-line; 409 second-line. 683 children (349 DTG, 334 SOC) consented to extended follow-up (97% of 707 approached). Overall, median follow-up was 5.5 years (286 weeks; IQR: 234-310). At 192 weeks, only 13% of SOC had switched to DTG, without prior treatment failure. 76(19%) DTG vs. 129(32%) SOC participants experienced treatment failure by 192 weeks (treatment difference [95% CI]:-13.3%[-19.2,-6.5]; p<0.001). Treatment effects were similar on first- and second-line [heterogeneity p=0.22]. Mean change in CD4% from baseline to week 192 was 12% in DTG versus 11% in SOC (difference (DTG-SOC) 1.4[95% CI:-0.2,3.0]; p=0.095). 11 children had died (4 DTG, 7 SOC) and 18 children had experienced a new/recurrent WHO4/severe WHO 3 event (9 DTG, 9 SOC) by week 192. By the end of follow-up, 309 (77% of randomised, 99% of those completing extended follow-up) of SOC arm had switched to DTG; 297(95%) of DTG arm remained on DTG. 248/275(90%) SOC participants switching to DTG were virologically suppressed post-switch (ODYSSEY A 96%, B 86%), including 179/193(93%) of those suppressed pre-switch (A 99%, B 89%) and 29/35(83%) with pre-switch VL≥400c/mL (A 87%, B 80%).
Conclusions:
Superior efficacy of DTG-based ART versus SOC was maintained up to 192 weeks in children starting both first- or second-line ART. On average, for every eight children treated with DTG versus alternative ART, one treatment failure will be prevented.