Predictors of treatment failure in children living with HIV starting first-line antiretroviral therapy in the ODYSSEY trial.

Abstract

Data on predictors of treatment failure in children starting antiretroviral therapy (ART) are limited, particularly on dolutegravir-based regimens (DTG). ODYSSEY demonstrated superior efficacy of DTG versus standard-of-care (SOC). We assessed predictors at ART initiation of treatment failure by 96 weeks. 381 children started first-line ART (82% African). At ART-initiation, median age was 10.5 years (IQR:6.5,14.0, 67<3 years), CD4% 20% (IQR:12, 28), BMI-for-age Z-score -0.58 (IQR:-1.48,+0.25). 189 children started DTG, 192 started SOC (91%≥3 years started efavirenz; 79%<3 years started lopinavir). 75 children experienced treatment failure (24 DTG, 51 SOC). Failure risk was lower on DTG than SOC (HR=0.47, 95%CI:0.29-0.77, p=0.002). Lower BMI-for-age Z-score (HR=0.82 for each unit gain, 95%CI:0.70-0.96, p=0.01) and being at an African site (HR=2.09, 95%CI:0.82-5.31, p=0.09) were associated with higher failure risk. Risk was also higher at younger ages with the steepest increase in the youngest children, and increased at lower CD4%, with a stronger CD4% effect at younger ages. At CD4%=20, hazard ratios relative to age 10 years were 2.40 (95%CI: 1.58-3.65) at age 1 year, 1.30 (95%CI: 1.15-1.48) at age 5 years and 0.80 (95%CI: 0.72-0.89) at age 18 years. At age 1 year, hazard ratios relative to CD4%=20 were 1.39 (95%CI: 1.16-1.66) at CD4%=15, and 0.52 (95%CI: 0.36-0.75) at CD4%=30; at age 10 corresponding estimates were 1.07 (95%CI: 0.94-1.20) at CD4%=15, and 0.88 (95%CI: 0.69-1.13) at CD4%=30. Young age, low BMI-for-age and low CD4% at ART initiation predicted higher risk of treatment failure and can guide targeted support.