Low response to pegylated interferon plus ribavirin in HIV-infected patients with chronic hepatitis C treated with abacavir

• Published in: Antiviral therapy 2008-01, Vol.13 (3), p.429-437
• Main Authors: VISPO, Eugenia, BARREIRO, Pablo, RIVERO, Antonio, SORIANO, Vincent, PINEDA, Juan A, MIRA, José A, MAIDA, Ivana, MARTIN-CARBONERO, Luz, RODRIGUEZ-NOVOA, Sonia, SANTOS, Ignacio, LOPEZ-CORTES, Luis F, MERINO, Dolores
• Format: Article
• Language: English
• Subjects: Adult; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antiviral agents; Antiviral Agents - blood; Antiviral Agents - therapeutic use; Biological and medical sciences; Dideoxynucleosides - therapeutic use; Drug Interactions; Drug Therapy, Combination; Hepacivirus - drug effects; Hepacivirus - genetics; Hepatitis C virus; Hepatitis C, Chronic - complications; Hepatitis C, Chronic - drug therapy; Hepatitis C, Chronic - genetics; HIV Infections - complications; HIV Infections - drug therapy; HIV Infections - virology; Human immunodeficiency virus; Human viral diseases; Humans; Immunodeficiencies; Immunodeficiencies. Immunoglobulinopathies; Immunopathology; Infectious diseases; Interferon-alpha - therapeutic use; Male; Medical sciences; Odds Ratio; Pharmacology. Drug treatments; Polyethylene Glycols - therapeutic use; Recombinant Proteins; Retrospective Studies; Reverse Transcriptase Inhibitors - therapeutic use; Ribavirin - blood; Ribavirin - therapeutic use; Risk Assessment; RNA, Viral - blood; Spain; Treatment Failure; Viral diseases; Viral diseases of the lymphoid tissue and the blood. Aids; Viral hepatitis; Viral Load
• ISSN: 1359-6535; 2040-2058
• DOI: 10.1177/135965350801300303

There is little information about the influence of antiretroviral drugs on the antiviral activity of pegylated interferon (PEG-IFN) plus ribavirin (RBV) against hepatitis C virus (HCV). All HIV-infected patients with chronic hepatitis C who received first-line PEG-IFN plus RBV were retrospectively analyzed. Only patients in whom virological stopping rules were applied and who did not change their antiretrovirals were chosen. Plasma RBV concentrations were measured at week 4. A total of 493 patients (78% males, mean age 41 years, 78% on antiretroviral therapy, mean CD4+ T-cell count 561 cells/microl) fit the study inclusion criteria. Mean baseline serum HCV RNA was 5.89 log10 IU/ml, 65% were infected by genotypes 1 or 4 and 40% had advanced liver fibrosis (Metavir F3F4). The overall rate of sustained virological response (SVR) was 38%. Factors associated with lack of SVR in the multivariate analyses (odds ratio [95% confidence interval], P-value) were higher baseline serum HCV RNA (2.42 per log10 IU/ml [1.31-4.46], 0.005), HCV genotypes 1 or 4 (5.95 [2.50-14.29], < 0.001) and lower RBV plasma trough concentrations (1.74 per microg/ml [1.15-2.63], 0.009). Interestingly, a trend was noticed for abacavir use (2.22 [0.91-5.40], 0.08), which become significant when only considering the subset of patients with RBV plasma levels < 2.3 microg/ml (7.63 [1.39-41.67], 0.02). The use of abacavir might interfere with the anti-HCV activity of PEG-IFN plus RBV. As both antivirals are guanosine analogues, an inhibitory competition between abacavir and RBV might explain this observation, which is more prominent in patients with lower RBV exposure.