Incidence of and Risk Factors for Severe Hepatotoxicity Associated with Antiretroviral Combination Therapy

This retrospective cohort study investigated whether particular antiretroviral agents are associated with a higher risk for developing grade 4 liver enzyme elevations (LEEs) in patients with human immunodeficiency virus (HIV) type 1 infection who are starting to receive highly active antiretroviral...

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Bibliographic Details
Published in:The Journal of infectious diseases 2002-07, Vol.186 (1), p.23-31
Main Authors: Wit, Ferdinand W. N. M., Weverling, Gerrit Jan, Weel, Jan, Jurriaans, Suzanne, Lange, Joep M. A.
Format: Article
Language:English
Subjects:
Adult
AIDS
Alanine Transaminase - blood
Anti-HIV Agents - adverse effects
Antiretroviral Therapy, Highly Active
Antiretrovirals
Antivirals
Biological and medical sciences
Chemical and Drug Induced Liver Injury - epidemiology
Chemical and Drug Induced Liver Injury - etiology
Cohort Studies
Drug toxicity and drugs side effects treatment
Female
Grade 4
Hepatitis B - complications
Hepatitis B virus
Hepatitis C - complications
Hepatotoxicity
HIV
HIV Infections - complications
HIV Infections - drug therapy
HIV-1
Humans
Incidence
Infections
Lamivudine - administration & dosage
Liver Function Tests
Major Article
Male
Medical sciences
Nevirapine - adverse effects
Pharmacology. Drug treatments
Predisposing factors
Proportional Hazards Models
Retrospective Studies
Reverse Transcriptase Inhibitors - administration & dosage
Risk Factors
Ritonavir - adverse effects
Sex Factors
Toxicity: digestive system
Transaminases - analysis
Viral hepatitis
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Summary:This retrospective cohort study investigated whether particular antiretroviral agents are associated with a higher risk for developing grade 4 liver enzyme elevations (LEEs) in patients with human immunodeficiency virus (HIV) type 1 infection who are starting to receive highly active antiretroviral therapy (HAART). Grade 4 LEE was defined as aminotransferase levels >10 times the upper limit of normal and >200 U above baseline levels. A multivariate Cox model was used to identify risk factors. The incidence of LEE was 6.3%. No patients died of LEE consequences. Risk factors were higher baseline alanine aminotransferase levels, chronic hepatitis B or C virus infection, antiretroviral therapy–naive patients undergoing their first HAART regimen, recent start of a regimen of nevirapine or high-dose ritonavir, and female sex. In hepatitis B virus (HBV)–coinfected patients, discontinuing lamivudine (3TC) use was a risk factor. In 97% of cases, ⩾1 risk factor was present. In HBV-coinfected patients using 3TC, continued use of 3TC should be considered, even if 3TC-resistant HIV strains develop
ISSN:0022-1899
1537-6613
DOI:10.1086/341084