Hepatic and Renal Toxicity and Associated Factors among HIV-Infected Children on Antiretroviral Therapy: A Prospective Cohort Study
The aim of the study was to investigate the prevalence of renal function and liver enzyme abnormalities among HIV‐infected children, changes in prevalence with time on combination antiretroviral therapy (cART), and the factors associated with these abnormalities.
A prospective cohort study was conducted among HIV‐infected children < 18 years old (n = 705) who were on first‐line cART. Liver enzymes, renal function, haematology, immunology and virological response were assessed at enrolment and followed bi‐annually for 18 months. Liver fibrosis and cirrhosis were assessed using noninvasive markers including the aspartate aminotransferase (AST) to platelet ratio index (APRI) and fibrosis score (FIB‐4).
The median age was 12 [interquartile range (IQR) 8–14] years; 53.3% of patients were male. At enrolment, the median cART duration was 3.3 (IQR 1.1–6.1) years; 177 (25.1%) and 83 (11.8%) patients had elevated AST and alanine aminotransferase (ALT), respectively. A tenth of the children had an APRI score > 0.5, suggesting liver fibrosis. Being on a zidovudine (ZDV)‐ or nevirapine (NVP)‐based regimen and having a viral load > 1000 HIV‐1 RNA copies/mL were significantly associated with elevated ALT. Twenty‐four (3.4%) and 84 (12.1%) patients had elevated creatinine and blood urea nitrogen (BUN), respectively. As cART duration increased by 6 months, median BUN increased by 1.6 [95% confidence interval (CI) 0.4–2.7] mg/dL (P = 0.01); the glomerular filtration rate (GFR) decreased by 35.6 (95% CI 17.7–53.4) mL/min/1.73 m2 (P < 0.0001); and AST and ALT decreased by 1.4 (95% CI 0.4–2.5) IU/L (P = 0.01) and 1.4 (95% CI 0.2–2.6) IU/L (P = 0.01), respectively.
A high prevalence of liver enzyme and renal function abnormalities was observed at enrolment. Decreasing liver enzyme levels during follow‐up are possibly reassuring, while the progressive reduction in GFR and the increase in BUN are worrisome and require further study.