Pretreatment of chronic active hepatitis C in patients coinfected with HIV and hepatitis C virus reduces the hepatotoxicity associated with subsequent antiretroviral therapy

Chronic hepatitis C virus (HCV) is an independent risk factor for antiretroviral-related hepatotoxicity, but little is known about the frequency of severe liver toxicity in patients with HIV-HCV coinfection first treated for HCV (pretreated). The aim of this prospective study of 105 patients was to compare the incidence of progression to severe antiretroviral-related liver toxicity in 66 patients pretreated (36 with interferon-alpha [IFNalpha], 30 with IFNalpha plus ribavirin), and 39 patients not pretreated. The subjects could choose whether to receive anti-HCV therapy. Severe liver toxicity was defined as alanine aminotransferase (ALT) level > or =5-times the upper limit of normal in patients with normal baseline levels and > or =3.5-times in those with increased baseline levels. The authors also estimated the hepatotoxicity-related risk of discontinuing antiretroviral therapy. During antiretroviral therapy, 10 subjects (9.5%) experienced severe hepatotoxicity: 4 of 66 pretreated patients and 6 of 39 untreated patients (24-month survival: 94% +/- 2.9% vs. 85% +/- 5.8%). After adjusting for baseline CD4 cell counts, ALT levels, histologic scores, HCV and HIV viremia, HCV genotype (genotype 1 in 29% of pretreated patients and 20% of patients not pretreated), and previous anti-HCV therapy, the risk of discontinuing anti-HIV treatment was significantly higher in the anti-HCV untreated patients (RR = 10.4; 95% CI: 1.6-66; p =.0127) and in those with increased baseline ALT levels (RR = 1.014; 95% CI: 1.006-1.021; p =.0005). The authors' data suggest that previous treatment of chronic active HCV is an independent factor associated with a decrease of severe liver toxicity as the result of a subsequent antiretroviral regimen. The authors also confirm that the baseline level of ALT is an important prognostic factor for increased liver damage during antiretroviral therapy.