In this study we analyzed the influence of human immunodeficiency virus (HIV) infection on the course of chronic hepatitis C through multivariate analysis including age, alcohol consumption, immune status, and hepatitis C virus (HCV)-related virologic factors. Eighty HIV-positive and 80 HIV-negative injection drug users included between 1980 and 1995 were matched according to age, gender, and duration of HCV infection and followed-up during 52 months. The progression to cirrhosis was the primary outcome measure. The impact of HIV on HCV-RNA load, histologic activity index, response to interferon therapy, and liver-related death was also considered. In HIV-positive patients, chronic hepatitis C was characterized by higher serum HCV-RNA levels (P ‫؍‬ .012), higher total Knodell score (P ‫؍‬ .011), and poorer sustained response to interferon therapy (P ‫؍‬ .009). High serum HCV-RNA level was associated with low CD4-lymphocyte count (P ‫؍‬ .001). Necroinflamatory score was higher in HIV-positive patients (P ‫؍‬ .023) independently of the CD4-lymphocyte count, whereas increased fibrosis was related to decreased CD4-lymphocyte count (P ‫؍‬ .011). The progression to cirrhosis was accelerated in HIV-positive patients with low CD4 cell count (RR ‫؍‬ 4.06, P ‫؍‬ .024) and in interferon-untreated patients (RR ‫؍‬ 4.76, P ‫؍‬ .001), independently of age at HCV infection (P ‫؍‬ .001). Cirrhosis caused death in 5 HIV-positive patients. The risk of death related to cirrhosis was increased in heavy drinkers (RR ‫؍‬ 10.8, P ‫؍‬ .001) and in HIV-positive patients with CD4 cell count less than 200/mm 3 (RR ‫؍‬ 11.9, P ‫؍‬ .007). In this retrospective cohort study, HIV coinfection worsened the outcome of chronic hepatitis C, increasing both serum HCV-

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