Severe hepatic cytolysis: incidence and risk factors in patients treated by antiretroviral combinations Aquitaine Cohort, France, 1996-1998

Objective: To study hepatic cytolysis in patients treated by highly active antiretroviral therapy (HAART) with protease inhibitor or with two nucleosi de reverse transcriptase inhibitors (NRTIs). Methods: We selected patients of the Aquitaine Cohort who initiated HAART o r two NRTIs before 1 January 1998, had alanine amino-transferase (ALT)less than or equal to 200 IU/I at baseline and at least one follow-up measure. C ox model was used to study the association between occurrence of severe hep atic cytolysis (ALT>200 IU/I) and age, gender, HIV transmission group, base line CD4 and CD8 cell count, history of hepatic cytolysis, antiretroviral d rug, baseline liver enzymes (WHO classification level 0: % 50 IU/I, level 1 : 57 to 100, level 2. 101 to 200), hepatitis B and C co-infection. Results: Sixty-four of 748 (8.5%) patients treated with HAART and 71 of 124 9 (5.7%) treated with two NRTIs developed cytolysis. The probability of occ urrence was 7.9% after 1 year [95% confidence interval (CI), 5.9-10.4] for patients treated with HAART and 4.8% (95% CI, 3.6-6.4) for patients treated with two NRTIs (log-rank test, P = 0.01). The median time to occurrence wa s 164 days for HAART-treated patients and 252 days for those treated with t wo NRTIs. In multivariate analysis, the history of cytolysis [hazard ratio (HR) = 2.3; 95% CI, 1.2-4.4], baseline value of ALT (HR = 2.4; 95% Cl, 1.2- 4.8 and HR = 3.3; 95% CI, 1.4-7.4 for levels 1 and 2, respectively), hepati tis B (HR = 3.0; 95%:, CT, 1.4-6.2) and C co-infections (HR = 3.2; 95% CI, 1.7-6.2) remained significantly associated with the occurrence of severe he patic cytolysis among HAART-treated patients. History of cytolysis, hepatit is B and C were associated with cytolysis in patients treated with two NRTI s (HR = 14.8, 2.6 and 2.7, respectively). Conclusion: Hepatic cytolysis is more frequent among patients treated with HAART than with two NRTIs. Hepatitis B and C are the major risk factors aft er initiation of HAART or treatment with NRTIs. Go-infections with hepatiti s B virus or hepatitis C virus may modify the management of HIV-infected pa tients treated by HAART. (C) 1999 Lippincott Williams & Williams.