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


CONCLUSIONS
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 PIs or efavirenz decreases and use of dydeoxynucleoside analogues increases the risk of hepatotoxicity.
Labarga
Pablo
P
Department of Infectious Diseases, Hospital Carlos III, Madrid 28029, Spain.
Soriano
Vicente
V
Vispo
Maria Eugenia
ME
Pinilla
Javier
J
Martin-Carbonero
Luz
L
Castellares
Carol
C
Casado
Rebeca
R
Maida
Ivana
I
Garcia-Gasco
Pilar
P
Barreiro
Pablo
P
D000328:Adult; D044966:Anti-Retroviral Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D023241:Antiretroviral Therapy, Highly Active / Q000009:adverse effects; D056486:Chemical and Drug Induced Liver Injury / Q000473:pathology / Q000517:prevention & control*; D005260:Female; D015658:HIV Infections / Q000150:complications* / Q000188:drug therapy; D016174:Hepacivirus / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000150:complications* / Q000188:drug therapy*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use; D008103:Liver Cirrhosis; D008297:Male; D011092:Polyethylene Glycols / Q000627:therapeutic use; D011994:Recombinant Proteins; D012254:Ribavirin / Q000627:therapeutic use
D044966:Anti-Retroviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; C100416:peginterferon alfa-2a