Risk factors for severe hepatic injury after introduction of highly active antiretroviral therapy

J Acquir Immune Defic Syndr. 2001 Aug 15;27(5):426-31. doi: 10.1097/00126334-200108150-00002.

Abstract

Objectives: Treatment of HIV infection with highly antiretroviral therapy (HAART) may be limited by liver toxicity. Its incidence and risk factors are not well known.

Patients and methods: Retrospective chart review. Naive patients beginning HAART between January 1997 and January 2000. Severe transaminase elevation was defined as fivefold or higher rise over upper normal limits, or as > or =3.5-fold rise above abnormal baseline values.

Results: Of 222 study subjects, 38%, 5%, and 2% were coinfected with hepatitis C virus (HCV), hepatitis B virus, and hepatitis D virus, respectively. Besides two nucleoside reverse transcriptase inhibitors (NRTIs), 96 patients received protease inhibitors (PIs), 90 received nonnucleoside reverse transcriptase inhibitors (NNRTIs), and 35 received a PI + NNRTI combination. Severe hepatic injury developed in 21 (9%): 10% PI, 9%, and 9% PI + NNRTI. Both univariate and multivariate analyses identified alcohol abuse, HCV coinfection, and older age as independent risk factors. Predictor variables in the final multivariate model were: alcohol abuse (risk ratio [RR], 5.87; 95% confidence interval [CI], 1.49-23.15; p =.01], positive HCV serology (RR, 3.99; 95% CI, 1.32-12.10; p =.01], and older age (RR, 1.11; 95% CI, 1.04-1.18; p = 0.001).

Conclusions: Nearly 10% of study subjects who start HAART experience severe transaminase elevation, irrespective of the treatment. Avoidance of alcohol abuse, especially in study subjects coinfected with HCV, will reduce the risk of hepatic injury after HAART. When possible, prior treatment for chronic HCV infection should be considered.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Alanine Transaminase / blood
  • Anti-HIV Agents / adverse effects*
  • Antiretroviral Therapy, Highly Active / adverse effects*
  • Aspartate Aminotransferases / blood
  • Chemical and Drug Induced Liver Injury*
  • Female
  • HIV Infections / complications
  • HIV Infections / drug therapy*
  • Hepatitis, Viral, Human / diagnosis
  • Humans
  • Incidence
  • Liver / enzymology
  • Liver / pathology*
  • Liver Diseases / epidemiology
  • Liver Diseases / pathology
  • Male
  • Middle Aged
  • Retrospective Studies
  • Reverse Transcriptase Inhibitors / adverse effects*
  • Risk Factors
  • Treatment Outcome

Substances

  • Anti-HIV Agents
  • Reverse Transcriptase Inhibitors
  • Aspartate Aminotransferases
  • Alanine Transaminase