title: HCV RNA assay sensitivity impacts the management of patients treated with direct-acting antivirals.
abstract: BACKGROUND
  Application of response-guided therapy (RGT) rules to the treatment of HCV infection with pegylated interferon-α2a and ribavirin, and direct-acting antivirals (DAAs) such as the NS3/4A protease inhibitors (PIs) boceprevir and telaprevir, relies on the determination of viral genotype and on-treatment HCV RNA level. Currently there are few data available regarding the clinical impact of the analytical differences that exist between different HCV RNA quantification assays on treatment decisions such as those involved in RGT.
  
  
  METHODS
  We sought to ascertain the concordance between two HCV RNA quantification assays, the Roche/High-Pure-System COBAS(®) TaqMan (CTM) version 2 and Abbott RealTime HCV (ART), and to understand the impact of different assay characteristics on treatment decisions. We evaluated 1,336 specimens collected from 74 patients enrolled in the Phase II CHAMPION-2 study of the investigational DAAs ABT-450 (an acylsulfonamide NS3/4A PI), ABT-072 and ABT-333 (both non-nucleoside NS5B polymerase inhibitors).
  
  
  RESULTS
  HCV RNA level results were highly correlated, but CTM values were higher than those from ART by an average of 0.46 log IU/ml. Use of ART HCV RNA level results led to a higher positive predictive value of week 4 viral load for the achievement of a sustained virological response 24 weeks after the end of treatment (100% versus 87% using the lower limit of detection as the threshold).
  
  
  CONCLUSIONS
  This study suggests that HCV viral load assay performance characteristics need to be taken into consideration when managing HCV patients with RGT. Further studies are required to determine whether a consensus HCV RNA level threshold can be established or whether HCV viral load assays with greater sensitivity can increase cure rates with RGT.
authors.affiliation: Abbott Molecular, Des Plaines, IL, USA.
authors.forename: Gavin
authors.initials: G
authors.lastname: Cloherty
authors.forename: Daniel
authors.initials: D
authors.lastname: Cohen
authors.forename: Christoph
authors.initials: C
authors.lastname: Sarrazin
authors.forename: Heiner
authors.initials: H
authors.lastname: Wedemeyer
authors.forename: Stephane
authors.initials: S
authors.lastname: Chevaliez
authors.forename: Christine
authors.initials: C
authors.lastname: Herman
authors.forename: Barry
authors.initials: B
authors.lastname: Bernstein
authors.forename: Jean Michel
authors.initials: JM
authors.lastname: Pawlotsky
mesh_terms: D015081:2-Naphthylamine; D000998:Antiviral Agents / Q000627:therapeutic use*; D001681:Biological Assay / Q000592:standards; D003521:Cyclopropanes; D016903:Drug Monitoring; D004359:Drug Therapy, Combination; D016174:Hepacivirus / Q000187:drug effects / Q000502:physiology; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use; D047029:Lactams, Macrocyclic; D047028:Macrocyclic Compounds / Q000627:therapeutic use; D009842:Oligopeptides / Q000627:therapeutic use; D011092:Polyethylene Glycols / Q000627:therapeutic use; D011392:Proline / Q000031:analogs & derivatives / Q000627:therapeutic use; D012367:RNA, Viral / Q000032:analysis* / Q000037:antagonists & inhibitors / Q000235:genetics; D011933:Reagent Kits, Diagnostic / Q000592:standards; D011994:Recombinant Proteins / Q000627:therapeutic use; D012254:Ribavirin / Q000627:therapeutic use; D012680:Sensitivity and Specificity; D013449:Sulfonamides / Q000627:therapeutic use; D016896:Treatment Outcome; D014498:Uracil / Q000031:analogs & derivatives / Q000627:therapeutic use; D019562:Viral Load / Q000187:drug effects*
chemical_list: D000998:Antiviral Agents; D003521:Cyclopropanes; D016898:Interferon-alpha; D047029:Lactams, Macrocyclic; D047028:Macrocyclic Compounds; D009842:Oligopeptides; D012367:RNA, Viral; D011933:Reagent Kits, Diagnostic; D011994:Recombinant Proteins; D013449:Sulfonamides; D011092:Polyethylene Glycols; D012254:Ribavirin; D014498:Uracil; C486464:telaprevir; C512204:N-(3-amino-1-(cyclobutylmethyl)-2,3-dioxopropyl)-3-(2-((((1,1-dimethylethyl)amino)carbonyl)amino)-3,3-dimethyl-1-oxobutyl)-6,6-dimethyl-3-azabicyclo(3.1.0)hexan-2-carboxamide; D011392:Proline; D015081:2-Naphthylamine; C588260:dasabuvir; C585405:paritaprevir; C100416:peginterferon alfa-2a