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Low Frequency of Severe Hepatotoxicity and Association With HCV Coinfection in HIV-Positive Patients Treated With HAART

Monforte Antonella d'Arminio; Bugarini, Roberto; Pezzotti, Patrizio; De Luca, Andrea; Antinori, Andrea; Mussini, Cristina; Vigevani, Gian Marco; Tirelli, Umberto; Bruno, Raffaele; Gritti, Francesco; Piazza, Marcello; Chigiotti, Silvia; Chirianni, Antonio; De Stefano, Carlo; Pizzigallo, Eligio; Perrella, Oreste; Moroni, Mauro; for the ICONA Study Group
JAIDS Journal of Acquired Immune Deficiency Syndromes: October 1st, 2001
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Background:Highly active antiretroviral therapy (HAART) is strongly effective in reducing morbidity and mortality in HIV-1-positive individuals. Its main drawback is the potential toxicity. Data on the frequency and determinants of severe hepatotoxicity in a clinical setting are still sparse.

Methods:This is a prospective study of HIV-1-positive individuals with known HBsAg and HCV-Ab serology. The study end point was progression to alanine aminotransferase (ALT) levels ≥200 IU/L after HAART initiation. Cumulative probability of progression to this end point was estimated by the Kaplan-Meier method. Crude and adjusted hazard ratios (HR) were estimated by proportional hazards regression model.

Results:One thousand two hundred fifty-five patients were included. HBsAg was found in 91 (7.2%), HCV-Ab in 578 (46.5%) patients; almost all injection drug users (451 of 482; 93.6%) were HCV-Ab positive. Sixty-one individuals progressed to the end point with a probability of 7.9% (95% confidence interval [CI], 5.6-10.0) of progression at 24 months from starting. Independent factors predicting progression to the end point were baseline ALT levels (HR, 5.29; 95% CI, 3.24-8.65; every 10 IU/L higher), HCV-Ab positivity (HR, 4.01; 95% CI, 1.48-10.85) or both HBsAg and HCV Ab positivity (HR, 3.85, 95% CI, 1.01-14.61), and previous non-HAART therapy (HR, 1.84, 95% CI, 1.04-3.42). Patients receiving stavudine-containing regimens had a lower risk than those receiving zidovudine-containing regimens (HR, 0.30, 95% CI, 0.12-0.71).

Conclusions:There was a low risk of ALT ≥200 IU/L in our cohort. Hepatitis C coinfection and elevated ALT levels at HAART initiation are important predictors of progression to ALT ≥200 IU/L; stavudine-containing regimens were associated with a lower risk compared with zidovudine-containing regimens.

Address correspondence and reprint requests to Antonella d'Arminio Monforte, MD, PhD, Institute of Infectious and Tropical Diseases, University of Milan, L Sacco Hospital - Via GB Grassi 74, 20157 Milan, Italy; e-mail:;

Manuscript received March 8, 2001; accepted June 5, 2001. This study was presented in part at the XIII International AIDS Conference, Durban, July 9-14 2000 (Abstr TuPpB1161).

© 2001 Lippincott Williams & Wilkins, Inc.