title: Pharmacodynamics of PEG-IFN-[alpha]-2a and HCV response as a function of IL28B polymorphism in HIV/HCV-coinfected patients.
abstract: We examined the association between IL28B single-nucleotide polymorphism rs12979860, hepatitis C virus (HCV) kinetic, and pegylated interferon alpha-2a pharmacodynamic parameters in HIV/HCV-coinfected patients from South America. Twenty-six subjects received pegylated interferon alpha-2a + ribavirin. Serum HCV-RNA and interferon concentrations were measured frequently during the first 12 weeks of therapy and analyzed using mathematical models. African Americans and whites had a similar distribution of IL28B genotypes (P = 0.5). The IL28B CC genotype was overrepresented (P = 0.015) in patients infected with HCV genotype-3 compared with genotype-1. In both genotype-1 and genotype-3, the first-phase viral decline and the average pegylated interferon-alpha-2a effectiveness during the first week of therapy were larger (trend P <= 0.12) in genotype-CC compared with genotypes-TC/TT. In genotype-1 patients, the second slower phase of viral decline (days 2-29) and infected cells loss rate, [delta], were larger (P = 0.02 and 0.11, respectively) in genotype-CC than in genotypes-TC/TT. These associations were not observed in genotype-3 patients.
authors.affiliation: Department of Infectious Diseases, University of São Paulo Hospital das Clínicas, São Paulo, Brazil. evaldostanislau@uol.com.br
authors.forename: Evaldo Stanislau Affonso
authors.initials: ES
authors.lastname: de Araujo
authors.forename: Harel
authors.initials: H
authors.lastname: Dahari
authors.forename: Scott J
authors.initials: SJ
authors.lastname: Cotler
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Layden
authors.forename: Avidan U
authors.initials: AU
authors.lastname: Neumann
authors.forename: Carlos Eduardo
authors.initials: CE
authors.lastname: Melo
authors.forename: Antonio Alci
authors.initials: AA
authors.lastname: Barone
mesh_terms: D000998:Antiviral Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D044383:Black People; D015658:HIV Infections / Q000150:complications*; D019698:Hepatitis C, Chronic / Q000150:complications* / Q000188:drug therapy*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage / Q000493:pharmacokinetics*; D007372:Interferons; D007378:Interleukins / Q000235:genetics*; D008962:Models, Theoretical; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000493:pharmacokinetics*; D020641:Polymorphism, Single Nucleotide; D012367:RNA, Viral / Q000097:blood; D011994:Recombinant Proteins; D012254:Ribavirin / Q000008:administration & dosage; D044967:Serum / Q000737:chemistry / Q000821:virology; D013020:South America; D019562:Viral Load; D044465:White People; D001741:Black or African American; D000095022:Interferon Lambda
chemical_list: D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D007372:Interferons; D007378:Interleukins; D011092:Polyethylene Glycols; D012367:RNA, Viral; D011994:Recombinant Proteins; D012254:Ribavirin; C000624353:interferon-lambda, human; D000095022:Interferon Lambda; C100416:peginterferon alfa-2a