Hepatic and Renal Toxicity and Associated Factors among HIV-Infected Children on Antiretroviral Therapy: A Prospective Cohort Study

Journal Article
  • Birkneh Tilahun Tadesse
  • B.A. Foster
  • A. Kapeta
  • G.H. Meskel
  • D. Jerene
  • E. Makonnen
  • E. Aklillu
HIV Medicine
2019; Vol. 20 (2): 147-56. DOI: https://doi.org/10.1111/hiv.12693.



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.