title: Efficacy of re-treatment with TMC435 as combination therapy in hepatitis C virus-infected patients following TMC435 monotherapy.
abstract: In the TMC435-C101 study, 6 patients infected with hepatitis C virus genotype 1 were treated with the protease inhibitor TMC435 (200 mg once daily) as monotherapy for 5 days. Approximately 1.5 years later, 5 of these patients were re-treated with TMC435 (200 mg once daily) plus pegylated interferon alfa-2a and ribavirin (PegIFNα-2a and RBV) for 4 weeks, followed by PegIFNα-2a and RBV until week 48 (in the Optimal Protease inhibitor Enhancement of Response to therApy [OPERA-1] study). TMC435-resistant variants, which emerged in all 5 patients during the TMC435-C101 study, were no longer detected at the beginning of the OPERA-1 study based on virus population sequencing. During the OPERA-1 study, 3 patients had a sustained virologic response; deep sequencing indicated low-level persistence of resistant variants in the remaining 2 patients, which might have affected their response to re-treatment.
authors.affiliation: Janssen Infectious Diseases, Beerse, Belgium. Electronic address: olenz@its.jnj.com.
authors.forename: Oliver
authors.initials: O
authors.lastname: Lenz
authors.affiliation: Department of Gastroenterology and Hepatology, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Joep
authors.initials: J
authors.lastname: de Bruijne
authors.affiliation: Janssen Infectious Diseases, Beerse, Belgium.
authors.forename: Leen
authors.initials: L
authors.lastname: Vijgen
authors.affiliation: Janssen Infectious Diseases, Beerse, Belgium.
authors.forename: Thierry
authors.initials: T
authors.lastname: Verbinnen
authors.affiliation: Department of Gastroenterology and Hepatology, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Christine
authors.initials: C
authors.lastname: Weegink
authors.affiliation: Janssen Infectious Diseases, Beerse, Belgium.
authors.forename: Herwig
authors.initials: H
authors.lastname: Van Marck
authors.affiliation: Janssen Infectious Diseases, Beerse, Belgium.
authors.forename: Ina
authors.initials: I
authors.lastname: Vandenbroucke
authors.affiliation: Janssen Infectious Diseases, Beerse, Belgium.
authors.forename: Monika
authors.initials: M
authors.lastname: Peeters
authors.affiliation: Janssen Infectious Diseases, Beerse, Belgium.
authors.forename: Kenneth
authors.initials: K
authors.lastname: Simmen
authors.affiliation: Janssen Infectious Diseases, Beerse, Belgium.
authors.forename: Greg
authors.initials: G
authors.lastname: Fanning
authors.affiliation: Janssen Infectious Diseases, Beerse, Belgium.
authors.forename: Rene
authors.initials: R
authors.lastname: Verloes
authors.affiliation: Janssen Research and Development, Titusville, New Jersey.
authors.forename: Gaston
authors.initials: G
authors.lastname: Picchio
authors.affiliation: Department of Gastroenterology and Hepatology, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Hendrik
authors.initials: H
authors.lastname: Reesink
mesh_terms: D000998:Antiviral Agents / Q000627:therapeutic use; D024882:Drug Resistance, Viral; D004359:Drug Therapy, Combination; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics*; D006526:Hepatitis C / Q000097:blood / Q000188:drug therapy* / Q000821:virology; D006575:Heterocyclic Compounds, 3-Ring / Q000627:therapeutic use*; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use; D008297:Male; D009154:Mutation; D011092:Polyethylene Glycols / Q000627:therapeutic use; D011480:Protease Inhibitors / Q000627:therapeutic use*; D012367:RNA, Viral / Q000097:blood* / Q000187:drug effects; D011994:Recombinant Proteins / Q000627:therapeutic use; D012254:Ribavirin / Q000627:therapeutic use; D000069616:Simeprevir; D013449:Sulfonamides / Q000627:therapeutic use*; D019562:Viral Load
chemical_list: D000998:Antiviral Agents; D006575:Heterocyclic Compounds, 3-Ring; D016898:Interferon-alpha; D011480:Protease Inhibitors; D012367:RNA, Viral; D011994:Recombinant Proteins; D013449:Sulfonamides; D011092:Polyethylene Glycols; D012254:Ribavirin; D000069616:Simeprevir; C100416:peginterferon alfa-2a