title: Role of pegylated interferon-alpha-2a and ribavirin concentrations in sustained viral response in HCV/HIV-coinfected patients.
abstract: The effect of simultaneous plasma concentrations of pegylated interferon-alpha-2a (pegIFN-alpha-2a) and ribavirin (Rbv) on viral response has not been addressed to date. Hepatitis C virus (HCV)/human immunodeficiency virus (HIV)-coinfected patients received pegIFN-alpha-2a and Rbv under routine clinical care conditions. Plasma concentrations of the two drugs were measured using enzyme-linked immunosorbent assay and high-performance liquid chromatography after 2, 4, 8, and 12 weeks and at the end of the treatment period (24-48 weeks, according to HCV genotype and treatment duration). Large interindividual variability was observed in the plasma levels of both drugs. After multivariate analysis, only HCV genotype 3, low HCV-RNA levels, and pegIFN-alpha-2a exposure remained as independent factors associated with sustained viral response (SVR). The probability of attaining an SVR in HCV genotypes 1 and 4 was more than three to four times higher in patients with pegIFN-alpha-2a levels above the selected cutoff point. Early therapeutic drug monitoring of pegIFN-alpha-2a levels could be beneficial in improving current treatment outcomes.
authors.affiliation: Instituto de Biomedicina de Sevilla, Servicio de Enfermedades Infecciosas, Hospitales Universitarios Virgen del Rocío, Seville, Spain. lflopez@telefonica.net
authors.forename: L F
authors.initials: LF
authors.lastname: Lopez-Cortes
authors.forename: B
authors.initials: B
authors.lastname: Valera-Bestard
authors.forename: A
authors.initials: A
authors.lastname: Gutierrez-Valencia
authors.forename: R
authors.initials: R
authors.lastname: Ruiz-Valderas
authors.forename: L
authors.initials: L
authors.lastname: Jimenez
authors.forename: A
authors.initials: A
authors.lastname: Arizcorreta
authors.forename: A
authors.initials: A
authors.lastname: Terrón
authors.forename: P
authors.initials: P
authors.lastname: Viciana
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use*; D002851:Chromatography, High Pressure Liquid; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000150:complications* / Q000188:drug therapy*; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics; D016174:Hepacivirus / Q000187:drug effects* / Q000235:genetics; D006526:Hepatitis C / Q000150:complications* / Q000188:drug therapy*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use*; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000009:adverse effects / Q000627:therapeutic use*; D011994:Recombinant Proteins; D012254:Ribavirin / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D014779:Virus Replication / Q000187:drug effects
chemical_list: D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; C100416:peginterferon alfa-2a