title: High interferon-stimulated gene ISG-15 expression affects HCV treatment outcome in patients co-infected with HIV and HCV.
abstract: Increased baseline expression and lack of induction of interferon-stimulated genes (ISG) are strong negative predictors of therapeutic response to PegIFN/RBV in patients co-infected with HIV and hepatitis C virus (HCV). This study specifically addressed whether ISG-15 expression influences therapeutic responses in 20 HIV/HCV genotype-1 subjects undergoing HCV treatment. Non-responders had significantly higher baseline expression and selective induction of ISG-15 after IFN-α treatment relative to participants with sustained virological response. High baseline levels of ISG-15 were also associated with less induction of ISG with treatment. These results support a role for ISG-15 as a prognostic indicator and resistance factor to IFN-α.
authors.affiliation: Department of Gastroenterology and Hepatology, University Hospital, Essen, Germany. osinusia@niaid.nih.gov
authors.forename: Antonios
authors.initials: A
authors.lastname: Katsounas
authors.forename: Jonathan J
authors.initials: JJ
authors.lastname: Hubbard
authors.forename: Crystal H
authors.initials: CH
authors.lastname: Wang
authors.forename: Xiaozhen
authors.initials: X
authors.lastname: Zhang
authors.forename: Diana
authors.initials: D
authors.lastname: Dou
authors.forename: Bhavana
authors.initials: B
authors.lastname: Shivakumar
authors.forename: Sophie
authors.initials: S
authors.lastname: Winter
authors.forename: Joerg F
authors.initials: JF
authors.lastname: Schlaak
authors.forename: Richard A
authors.initials: RA
authors.lastname: Lempicki
authors.forename: Henry
authors.initials: H
authors.lastname: Masur
authors.forename: Michael
authors.initials: M
authors.lastname: Polis
authors.forename: Shyam
authors.initials: S
authors.lastname: Kottilil
authors.forename: Anu
authors.initials: A
authors.lastname: Osinusi
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use*; D060085:Coinfection; D016207:Cytokines / Q000235:genetics* / Q000276:immunology; D005260:Female; D015870:Gene Expression / Q000187:drug effects*; D015658:HIV Infections / Q000188:drug therapy / Q000235:genetics* / Q000276:immunology / Q000821:virology; D015497:HIV-1; D016174:Hepacivirus / Q000235:genetics*; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology / Q000821:virology; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000627:therapeutic use*; D011446:Prospective Studies; D012367:RNA, Viral / Q000378:metabolism; D011994:Recombinant Proteins / Q000627:therapeutic use; D016896:Treatment Outcome; D014452:Ubiquitins / Q000235:genetics* / Q000276:immunology
chemical_list: D000998:Antiviral Agents; D016207:Cytokines; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D012367:RNA, Viral; D011994:Recombinant Proteins; D014452:Ubiquitins; D011092:Polyethylene Glycols; C074034:ISG15 protein, human; C417083:peginterferon alfa-2b