title: Effect of antiretroviral therapy on liver-related mortality in patients with HIV and hepatitis C virus coinfection.
abstract: BACKGROUND
  Highly active antiretroviral therapy (HAART) has improved the prognosis of HIV infection. However, replication of hepatitis C virus (HCV) is not inhibited by HAART, and treatment-related hepatotoxicity is common. To clarify the effect of HAART in HIV/HCV-coinfected patients, we studied liver-related mortality and overall mortality in 285 patients who were regularly treated during the period 1990-2002 at our department.
  
  
  METHODS
  Survival was analysed retrospectively by Kaplan-Meier and Cox's regression analyses after patients (81% haemophiliacs) had been stratified into three groups according to their antiretroviral therapy (HAART n=93, available after 1995; treatment exclusively with nucleoside analogues n=55, available after 1992; or no treatment, n=137).
  
  
  RESULTS
  Liver-related mortality rates were 0.45, 0.69, and 1.70 per 100 person-years in the HAART, antiretroviral-treatment, and untreated groups. Kaplan-Meier analysis of liver-related mortality confirmed the significant survival benefit in patients with antiretroviral therapy (p=0.018), and regression analysis identified HAART (odds ratio 0.106 [95% CI 0.020-0.564]), antiretroviral treatment (0.283 [0.103-0.780]), CD4-positive T-cell count (0.746 [0.641-0.868] per 0.05x10(9) cells/L), serum cholinesterase (0.962 [0.938-0.986] per 100 U/L), and age (1.065 [1.027-1.105] per year) as independent predictors of liver-related survival. Severe drug-related hepatotoxicity was seen in five patients treated with nucleoside analogues alone and 13 treated with HAART. No patient died from drug-related hepatotoxicity.
  
  
  CONCLUSIONS
  In addition to improved overall survival, antiretroviral therapy significantly reduced long-term liver-related mortality in our patients. This survival benefit seems to outweigh by far the associated risks of severe hepatotoxicity.
authors.affiliation: Department of Internal Medicine I, University of Bonn, Bonn, Germany.
authors.forename: Nazifa
authors.initials: N
authors.lastname: Qurishi
authors.forename: Christina
authors.initials: C
authors.lastname: Kreuzberg
authors.forename: Guido
authors.initials: G
authors.lastname: Lüchters
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Effenberger
authors.forename: Bernd
authors.initials: B
authors.lastname: Kupfer
authors.forename: Tilman
authors.initials: T
authors.lastname: Sauerbruch
authors.forename: Jürgen K
authors.initials: JK
authors.lastname: Rockstroh
authors.forename: Ulrich
authors.initials: U
authors.lastname: Spengler
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000009:adverse effects*; D023241:Antiretroviral Therapy, Highly Active; D015415:Biomarkers / Q000097:blood; D002423:Cause of Death; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology*; D018450:Disease Progression; D005260:Female; D015658:HIV Infections / Q000150:complications* / Q000188:drug therapy / Q000401:mortality*; D015497:HIV-1; D006526:Hepatitis C / Q000150:complications* / Q000401:mortality*; D006801:Humans; D008297:Male; D016016:Proportional Hazards Models; D016019:Survival Analysis
chemical_list: D019380:Anti-HIV Agents; D015415:Biomarkers