title: Comparison of three quantitative HCV RNA assays in samples from HCV genotype 1- or 4-infected patients treated with the NS3/4A protease inhibitor simeprevir.
abstract: BACKGROUND
  Monitoring HCV RNA levels during treatment is an important tool for managing protease-inhibitor-based regimens, and different assays used in clinical practice can impact treatment decisions.
  
  
  OBJECTIVE
  The concordance of three HCV RNA assays was determined, and their impact on treatment decisions assessed using samples from HCV genotype (GT) 1- and GT4-infected patients treated with the NS3/4A inhibitor simeprevir in combination with pegylated interferon-α/ribavirin.
  
  
  METHODS
  Plasma samples collected during the simeprevir Phase III studies QUEST-1 and QUEST-2 (GT1), and RESTORE (GT4) were analyzed with the Roche High-Pure-System COBAS(®) TaqMan(®) HCV v2.0 (HPS), the Roche AmpliPrep COBAS(®) TaqMan(®) HCV v2.0 (CAP), and the Abbott RealTime HCV (ART) assay.
  
  
  RESULTS
  In GT1, of the 440 samples, 81% were undetectable (rapid virological response; RVR) by HPS at Week 4, 76% by CAP and 44% by ART. In GT4 (103 samples), RVR rates were 67% by HPS and 24% by ART. HCV RNA <25IU/mL at Week 4 was observed for 95-96% and 92% GT1 samples and 86% and 74% GT4 samples by HPS/CAP and ART, respectively. At Week 12, assay concordance for undetectability was high in GT1 and GT4, (95-98% and 93%, respectively).
  
  
  CONCLUSIONS
  While different HCV RNA assays can lead to substantially different RVR rates, a good concordance was observed with a cut-off of 25IU/mL. Sustained virologic response rates among GT1 patients achieving RVR or <25IU/mL at Week 4 were high and similar between assays used. At later time points, when viremia is low, assay concordance was high.
authors.affiliation: Janssen Infectious Diseases BVBA, Beerse, Belgium. Electronic address: bfevery@its.jnj.com.
authors.forename: Bart
authors.initials: B
authors.lastname: Fevery
authors.affiliation: J.W. Goethe University, Medizinische Klinik 1, Frankfurt, Germany. Electronic address: susser@med.uni-frankfurt.de.
authors.forename: Simone
authors.initials: S
authors.lastname: Susser
authors.affiliation: Janssen Infectious Diseases BVBA, Beerse, Belgium. Electronic address: olenz@its.jnj.com.
authors.forename: Oliver
authors.initials: O
authors.lastname: Lenz
authors.affiliation: Abbott Molecular, Des Plaines, IL, USA. Electronic address: gavin.cloherty@abbott.com.
authors.forename: Gavin
authors.initials: G
authors.lastname: Cloherty
authors.affiliation: J.W. Goethe University, Medizinische Klinik 1, Frankfurt, Germany. Electronic address: perner@med.uni-frankfurt.de.
authors.forename: Dany
authors.initials: D
authors.lastname: Perner
authors.affiliation: Janssen Infectious Diseases BVBA, Beerse, Belgium. Electronic address: LGILLES@its.jnj.com.
authors.forename: Leen
authors.initials: L
authors.lastname: Gilles
authors.affiliation: Janssen Infectious Diseases BVBA, Beerse, Belgium. Electronic address: PDLOCHT1@its.jnj.com.
authors.forename: Patrick
authors.initials: P
authors.lastname: De Locht
authors.affiliation: Janssen Research & Development LLC, Titusville, NJ, USA. Electronic address: GPicchio@its.jnj.com.
authors.forename: Gaston
authors.initials: G
authors.lastname: Picchio
authors.affiliation: Janssen Infectious Diseases BVBA, Beerse, Belgium. Electronic address: SDMEYER@its.jnj.com.
authors.forename: Sandra
authors.initials: S
authors.lastname: De Meyer
authors.affiliation: J.W. Goethe University, Medizinische Klinik 1, Frankfurt, Germany. Electronic address: sarrazin@em.uni-frankfurt.de.
authors.forename: Christoph
authors.initials: C
authors.lastname: Sarrazin
mesh_terms: D000998:Antiviral Agents / Q000008:administration & dosage*; D017326:Clinical Trials, Phase III as Topic; D016903:Drug Monitoring / Q000379:methods*; D005838:Genotype; D016174:Hepacivirus / Q000145:classification / Q000235:genetics / Q000302:isolation & purification*; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000821:virology*; D006801:Humans; D016898:Interferon-alpha / Q000008:administration & dosage; D011480:Protease Inhibitors; D012367:RNA, Viral / Q000097:blood*; D012189:Retrospective Studies; D012254:Ribavirin / Q000008:administration & dosage; D000069616:Simeprevir / Q000008:administration & dosage; D019562:Viral Load / Q000379:methods*
chemical_list: D000998:Antiviral Agents; D016898:Interferon-alpha; D011480:Protease Inhibitors; D012367:RNA, Viral; D012254:Ribavirin; D000069616:Simeprevir
keywords: Assay concordance; DAA; HCV RNA quantification; HCV genotype 1 and 4; Response-guided treatment; Simeprevir