Incidence and risk factors for liver enzyme elevation during highly active antiretroviral therapy in HIV-HCV co-infected patients: results from the Italian EPOKA-MASTER Cohort

BMC Infect Dis. 2005 Jul 14:5:58. doi: 10.1186/1471-2334-5-58.


Background: The risk of hepatotoxicity associated with different highly active antiretroviral therapy (HAART) regimens (containing multiple-protease inhibitors, single-protease inhibitors or non nucleoside reverse transcriptase inhibitors) in HIV-HCV co-infected patients has not been fully assessed.

Methods: Retrospective analysis of a prospective cohort of 1,038 HIV-HCV co-infected patients who commenced a new HAART in the Italian MASTER database. Patients were stratified into naïve and experienced to antiretroviral therapy before starting the study regimens. Time to grade > or =III hepatotoxicity (as by ACTG classification) was the primary outcome. Secondary outcome was time to grade IV hepatotoxicity.

Results: Incidence of grade > or =III hepatotoxicity was 17.71 per 100 patient-years (p-yr) of follow up in naïve patient group and 8.22 per 100 p-yrs in experienced group (grade IV: 4.13 per 100 p-yrs and 1.08 per 100 p-yrs, respectively). In the latter group, the only independent factors associated with shorter time to the event at proportional hazards regression model were: previous liver transaminase elevations to grade > or =III, higher baseline alanine amino-transferase values, and use of a non nucleoside reverse transcriptase inhibitor based regimen. In the naive group, baseline aspartate transaminase level was associated with the primary outcome.

Conclusion: Use of a single or multiple protease inhibitor based regimen was not associated with risk of hepatotoxicity in either naïve or experienced patient groups to a statistically significant extent. A cautious approach with strict monitoring should be applied in HIV-HCV co-infected experienced patients with previous liver transaminase elevations, higher baseline alanine amino-transferase values and who receive regimens containing non nucleoside reverse transcriptase inhibitors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Alanine Transaminase
  • Anti-HIV Agents / adverse effects
  • Antiretroviral Therapy, Highly Active / adverse effects*
  • Aspartate Aminotransferases
  • Chemical and Drug Induced Liver Injury / etiology
  • Cohort Studies
  • HIV Infections / complications*
  • HIV Infections / drug therapy*
  • Hepatitis C / complications*
  • Humans
  • Incidence
  • Italy
  • Liver / drug effects*
  • Liver / enzymology*
  • Liver Function Tests
  • Middle Aged
  • Proportional Hazards Models
  • Retrospective Studies
  • Risk Factors


  • Anti-HIV Agents
  • Aspartate Aminotransferases
  • Alanine Transaminase