Influence of IL28B polymorphisms on response to a lower-than-standard dose peg-IFN-α 2a for genotype 3 chronic hepatitis C in HIV-coinfected patients

• Published in: PloS one Vol. 7; no. 1; p. e28115
• Main Authors: López-Cortés, Luis F, Ruiz-Valderas, Rosa, Jimenez-Jimenez, Luis, González-Escribano, María F, Torres-Cornejo, Almudena, Mata, Rosario, Rivero, Antonio, Pineda, Juan A, Marquez-Solero, Manuel, Viciana, Pompeyo
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 2012; Public Library of Science (PLoS)
• Subjects: Adult; Biology; Biopsy; Dose-Response Relationship, Drug; Female; Genotype; Genotype & phenotype; Genotypes; Hepatitis; Hepatitis C; Hepatitis C, Chronic - complications; Hepatitis C, Chronic - drug therapy; Hepatitis C, Chronic - genetics; Hepatitis C, Chronic - metabolism; Hepatology; HIV; HIV Infections - complications; Human immunodeficiency virus; Humans; Infections; Interferon; Interferon-alpha - adverse effects; Interferon-alpha - pharmacokinetics; Interferon-alpha - therapeutic use; Interferons; Interleukins - genetics; Liver; Male; Medicine; Middle Aged; Motivation; Patients; Polyethylene glycol; Polyethylene Glycols - adverse effects; Polyethylene Glycols - pharmacokinetics; Polyethylene Glycols - therapeutic use; Polymorphism, Single Nucleotide; Recombinant Proteins - adverse effects; Recombinant Proteins - pharmacokinetics; Recombinant Proteins - therapeutic use; Ribavirin; Ribavirin - pharmacokinetics; Ribavirin - therapeutic use; Ribonucleic acid; RNA; Safety; Therapy; Treatment Outcome; Viremia; α-Interferon; Spain
• DOI: 10.1371/journal.pone.0028115
• ISSN: 1932-6203

Data on which to base definitive recommendations on the doses and duration of therapy for genotype 3 HCV/HIV-coinfected patients are scarce. We evaluated the efficacy of a lower peginterferon-α 2a dose and a shorter duration of therapy than the current standard of care in genotype 3 HCV/HIV-coinfected patients. Pilot, open-label, single arm clinical trial which involved 58 Caucasian HCV/HIV-coinfected patients who received weekly 135 µg peginterferon-α 2a plus ribavirin 400 mg twice daily during 20 weeks after attaining undetectable viremia. The relationships between baseline patient-related variables, including IL28B genotype, plasma HCV-RNA, ribavirin dose/kg, peginterferon-α 2a and ribavirin levels with virological responses were analyzed. Only 4 patients showed lack of response and 5 patients dropped out due to adverse events related to the study medication. Overall, sustained virologic response (SVR) rates were 58.3% by intention-to-treat and 71.4% by per protocol analysis, respectively. Among patients with rapid virologic response (RVR), SVR and relapses rates were 92.6% and 7.4%, respectively. No relationships were observed between viral responses and ribavirin dose/kg, peginterferon-α 2a concentrations, ribavirin levels or rs129679860 genotype. Weekly 135 µg pegIFN-α 2a could be as effective as the standard 180 µg dose, with a very low incidence of severe adverse events. A 24-week treatment duration appears to be appropriate in patients achieving RVR, but extending treatment up to just 20 weeks beyond negativization of viremia is associated with a high relapse rate in those patients not achieving RVR. There was no influence of IL28B genotype on the virological responses. ClinicalTrials.gov NCT00553930.