Severe hepatic cytolysis: incidence and risk factors in patients treated by antiretroviral combinations. Aquitaine Cohort, France, 1996-1998. Groupe dEpidémiologie Clinique de Sida en Aquitaine (GECSA).
OBJECTIVE
To study hepatic cytolysis in patients treated by highly active antiretroviral therapy (HAART) with protease inhibitor or with two nucleoside reverse transcriptase inhibitors (NRTIs).


METHODS
We selected patients of the Aquitaine Cohort who initiated HAART or two NRTIs before 1 January 1998, had alanine amino-transferase (ALT) < or = 200 IU/I at baseline and at least one follow-up measure. Cox model was used to study the association between occurrence of severe hepatic cytolysis (ALT>200 IU/l) and age, gender, HIV transmission group, baseline CD4 and CD8 cell count, history of hepatic cytolysis, antiretroviral drug, baseline liver enzymes (WHO classification level 0: < or = 50 IU/l, level 1: 51 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 1249 (5.7%) treated with two NRTIs developed cytolysis. The probability of occurrence 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 was 164 days for HAART-treated patients and 252 days for those treated with two 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% CI, 1.2-4.8 and HR = 3.3; 95% CI, 1.4-7.4 for levels 1 and 2, respectively), hepatitis B (HR = 3.0; 95% CI, 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 hepatic cytolysis among HAART-treated patients. History of cytolysis, hepatitis B and C were associated with cytolysis in patients treated with two NRTIs (HR = 14.8, 2.6 and 2.7, respectively).


CONCLUSIONS
Hepatic cytolysis is more frequent among patients treated with HAART than with two NRTIs. Hepatitis B and C are the major risk factors after initiation of HAART or treatment with NRTIs. Co-infections with hepatitis B virus or hepatitis C virus may modify the management of HIV-infected patients treated by HAART.
Savès
M
M
INSERM U.330, Université Victor Segalen Bordeaux 2, France.
Vandentorren
S
S
Daucourt
V
V
Marimoutou
C
C
Dupon
M
M
Couzigou
P
P
Bernard
N
N
Mercié
P
P
Dabis
F
F
D000293:Adolescent; D000328:Adult; D000368:Aged; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000009:adverse effects*; D056486:Chemical and Drug Induced Liver Injury; D015331:Cohort Studies; D004359:Drug Therapy, Combination; D005260:Female; D005602:France; D015658:HIV Infections / Q000188:drug therapy*; D017320:HIV Protease Inhibitors / Q000008:administration & dosage / Q000009:adverse effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects; D012307:Risk Factors
D019380:Anti-HIV Agents; D017320:HIV Protease Inhibitors; D018894:Reverse Transcriptase Inhibitors