Effect of antiretroviral therapy on liver-related mortality in patients with HIV and hepatitis C virus coinfection

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 Coxʹs 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). Findings 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•05 × 109 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. Interpretation 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.