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The aim of this study was to evaluate the incidence and risk factors of severe liver events among HIV-infected patients treated with drug combinations including tipranavir boosted with ritonavir (TPV/r).One hundred and fifty patients were selected because they started a regimen that included TPV/r (500/200 mg twice a day) and had clinical visits at least every 3 months. Patients who discontinued TPV/r before their first visit were included.Twelve (8%) individuals developed grade ≥3 transaminase elevation (G ≥ 3TE). Nine (6%) patients discontinued TPV/r due to liver events. Six (8.6%) of 70 hepatitis C virus (HCV) co-infected patients and 6 (7.5%) of 80 subjects without HCV co-infection developed G ≥ 3TE (P=1). Liver fibrosis was evaluable in 48 (63%) of 76 individuals with hepatitis B virus and/or HCV infection. Four (13%) of 30 subjects with moderate-to-severe fibrosis and none of 18 with mild fibrosis showed G ≥ 3TE (P=0.3). None of nine patients with cirrhosis showed G ≥ 3TE.Liver tolerability of TPV/r was generally good in a cohort of patients with a high proportion of HCV co-infection, including subjects with advanced fibrosis. The presence of HCV co-infection was not associated with an increased risk of severe transaminase elevations.