Background We determined the prevalence and incidence of liver dysfunction prior to and after initiation of combination antiretroviral therapy (cART) in the TREAT Asia Pediatric HIV Observational Database (TApHOD). Methods Data from children initiated on cART between 2–18 years of age with baseline alanine aminotransferase (ALT) available prior to and at least once after cART initiation in TApHOD between 2008–2012 were analyzed. Prevalence and incidence of liver dysfunction, and biomarkers including the aspartate aminotransferase (AST) to platelet ratio index (APRI) and FIB4 index were assessed. Results Data from 1930 children were included. Their median age was 6.9 years; 49% were male; 98% were perinatally infected; and 94% were initiated on non-nucleoside reverse transcriptase-based cART regimens. Prior to cART, the prevalence of ALT ≥ 3 times the upper limit of normal (*ULN) was 5.8%. There were 8.5% of children with APRI >1.5 (suggestive of liver fibrosis), and 2.7% with FIB4 index >1.3 (predictive of possible cirrhosis). Among the 1143 cases with normal baseline ALT (≤1*ULN), the incidence of ALT 3*ULN after cART was 1.19/1000 person-months (95% CI 0.93–1.51). Two of 350 with available tests (0.6%) met Hy’s law (ALT >3*ULN and total bilirubin >2*ULN). By multivariate analysis, baseline hemoglobin <7.5 g/dL was a predictor of ALT >3*ULN, while age 5–9 years at cART initiation was protective for liver dysfunction. Conclusions We demonstrated a low prevalence and incidence of liver dysfunction before and after cART initiation in children with normal baseline chemistries. In this population facing life-long cART, prospective surveillance for emergence of liver disease is warranted.

Background Information on antiretroviral therapy (ART) use in HIV-infected children with severe malnutrition (SM) is lacking. We investigated long-term ART outcomes in this population. Methods Children enrolled in the TREAT Asia Pediatric HIV Observational Database who had SM (weight-for-height or BMI-for-age z-score <−3) at ART initiation were analyzed. Generalized estimating equations were used to investigate poor weight recovery (weight-for-age z-score <−3) and poor CD4% recovery (CD4% <25), and competing risk regression was used to analyze mortality and toxicity-associated treatment modification. Results Three hundred fifty five (11.9%) of 2993 children starting ART had SM. Their median weight-for-age z-score increased from −5.6 at ART initiation to −2.3 after 36 months. Not using cotrimoxazole prophylaxis at baseline was associated with poor weight recovery (OR 2.49 vs. using, 95%CI 1.66-3.74, p<0.001). Median CD4% increased from 3.0 at ART initiation to 27.2 after 36 months, and 56 (15.3%) children died during follow-up. More profound SM was associated with poor CD4% recovery (OR 1.78 for z-score <−4.5 vs. −3.5 to <−3.0, 95%CI 1.08-2.92, p=0.023) and mortality (HR 2.57 for z-score <−4.5 vs. −3.5 to <−3.0, 95%CI 1.24-5.33, p=0.011). Twenty two toxicity-associated ART modifications occurred at a rate of 2.4 per 100 patient-years and rates did not differ by malnutrition severity. Discussion Cotrimoxazole prophylaxis is important for the recovery of weight-for-age in severely malnourished children starting ART. The extent of SM does not impede weight-for-age recovery or antiretroviral tolerability but CD4% response is compromised in children with a very low weight-for-height/BMI-for-age z-score which may contribute to their high rate of mortality.