Hepatotoxicity of antiretroviral drugs is reduced after successful treatment of chronic hepatitis C in HIV-infected patients

Abstract

Background. The risk of liver toxicity during antiretroviral drug use in human immunodeficiency virus (HIV)-positive patients increases in the presence of chronic hepatitis C virus (HCV) infection. It is unknown whether sustained HCV clearance after interferon (IFN)-based therapy might reduce this complication. Methods. The incidence of severe elevations in liver enzyme levels during antiretroviral therapy was retrospectively analyzed in a group of HIV/HCV-coinfected patients after completion of a full course of IFN-based therapy. Hepatic events were recorded according to the achievement of a sustained virological response (SVR), and the presence of advanced liver fibrosis was assessed by transient elastometry Results. A total of 132 HIV/HCV-coinfected patients were analyzed (66% men; mean age, 38 years). Overall, 33% achieved an SVR and 40% had advanced liver fibrosis after IFN therapy. A total of 49 episodes of liver toxicity occurred during a mean of 35 months of follow-up (9.7% per year) after IFN therapy. The yearly incidence of hepatic events was greater in patients who did not achieve an SVR than in those who did (12.9% vs. 3.1%; P < .001) and in patients with advanced liver fibrosis than in those without it (14.4% vs. 7.6%; P = .003). Drugs involved in hepatic events were dydeoxynucleoside analogues (namely, didanosine and stavudine; 40%) nevirapine (30%), efavirenz (11%), and protease inhibitors (Pls; 8%). In logistic regression analysis, lack of an SVR (odds ratio [OR], 6.13 [95% confidence interval {CI}, 1.83-37.45]; P = .003) and the use of dydeoxynucleosides (OR, 3.59 [95% CI, 1.23-10.42]; P = .02) were independent predictors of hepatotoxicity after IFN therapy. Conversely, regimens containing Pls (OR, 0.07 [95% CI, 0.02-0.30]; P < .01) or efavirenz (OR, 0.13 [95% CI, 0.04-0.44]; P = .001) were associated with a diminished risk of hepatic events. Conclusion. Sustained HCV clearance after IFN-based therapy reduces the risk of liver toxicity during antiretroviral therapy, which should further encourage the treatment of chronic hepatitis C in HIV-coinfected patients. In this population, prescription of Pls or efavirenz decreases and use of dydeoxynucleoside analogues increases the risk of hepatotoxicity. © 2007 by the Infectious Diseases Society of America. All rights reserved.