Hepatic and renal toxicity and associated factors among HIV-infected children on antiretroviral therapy: a prospective cohort study

HIV Med. 2019 Feb;20(2):147-156. doi: 10.1111/hiv.12693. Epub 2018 Nov 26.

Abstract

Objectives: 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.

Methods: 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).

Results: 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.

Conclusions: 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.

Keywords: HIV infection; children and adolescents; combination antiretroviral therapy; toxicity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Anti-HIV Agents / adverse effects*
  • Anti-HIV Agents / pharmacology
  • Aspartate Aminotransferases / metabolism
  • Child
  • Ethiopia / epidemiology
  • Female
  • HIV Infections / drug therapy*
  • HIV Infections / metabolism
  • HIV-1 / drug effects
  • HIV-1 / genetics
  • Humans
  • Kidney Diseases / chemically induced
  • Kidney Diseases / epidemiology*
  • Kidney Function Tests
  • Liver Cirrhosis / chemically induced
  • Liver Cirrhosis / epidemiology*
  • Male
  • Prevalence
  • Prospective Studies
  • Viral Load / drug effects

Substances

  • Anti-HIV Agents
  • Aspartate Aminotransferases