title: Low frequency of severe hepatotoxicity and association with HCV coinfection in HIV-positive patients treated with HAART.
abstract: 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 > or =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 > or =200 IU/L in our cohort. Hepatitis C coinfection and elevated ALT levels at HAART initiation are important predictors of progression to ALT > or =200 IU/L; stavudine-containing regimens were associated with a lower risk compared with zidovudine-containing regimens.
authors.affiliation: Institute of Infectious and Tropical Diseases, University of Milan, L Sacco H, Milan, Italy. adarmin@tin.it
authors.forename: A de A
authors.initials: Ade A
authors.lastname: Monforte
authors.forename: R
authors.initials: R
authors.lastname: Bugarini
authors.forename: P
authors.initials: P
authors.lastname: Pezzotti
authors.forename: A
authors.initials: A
authors.lastname: De Luca
authors.forename: A
authors.initials: A
authors.lastname: Antinori
authors.forename: C
authors.initials: C
authors.lastname: Mussini
authors.forename: G M
authors.initials: GM
authors.lastname: Vigevani
authors.forename: U
authors.initials: U
authors.lastname: Tirelli
authors.forename: R
authors.initials: R
authors.lastname: Bruno
authors.forename: F
authors.initials: F
authors.lastname: Gritti
authors.forename: M
authors.initials: M
authors.lastname: Piazza
authors.forename: S
authors.initials: S
authors.lastname: Chigiotti
authors.forename: A
authors.initials: A
authors.lastname: Chirianni
authors.forename: C
authors.initials: C
authors.lastname: De Stefano
authors.forename: E
authors.initials: E
authors.lastname: Pizzigallo
authors.forename: O
authors.initials: O
authors.lastname: Perrella
authors.forename: M
authors.initials: M
authors.lastname: Moroni
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D019380:Anti-HIV Agents / Q000627:therapeutic use; D023241:Antiretroviral Therapy, Highly Active; D015331:Cohort Studies; D018450:Disease Progression; D005260:Female; D006679:HIV Seropositivity / Q000150:complications; D015497:HIV-1 / Q000302:isolation & purification; D006514:Hepatitis B Surface Antigens / Q000032:analysis; D006526:Hepatitis C / Q000150:complications*; D006801:Humans; D008297:Male; D016016:Proportional Hazards Models; D018119:Stavudine; D015215:Zidovudine / Q000627:therapeutic use
chemical_list: D019380:Anti-HIV Agents; D006514:Hepatitis B Surface Antigens; D015215:Zidovudine; D018119:Stavudine; D000410:Alanine Transaminase