title: HCV RNA quantification with different assays: implications for protease-inhibitor-based response-guided therapy.
abstract: BACKGROUND
  Response-guided therapy (RGT) for HCV treatment, whereby therapy duration is shortened according to on-treatment virological response, requires patient HCV RNA concentrations below the lower limit of quantification (LLOQ) or limit of detection (LOD) of the viral load assay at weeks 4 and 12. Concordance of two assays and impact on treatment decisions were investigated.
  
  
  METHODS
  Plasma samples (n=1,411; baseline to week 12) from HCV genotype-1-infected patients (n=290) receiving simeprevir (TMC435) plus pegylated interferon-α2a/ribavirin in the PILLAR study (NCT00882908) were analysed using Roche High-Pure-System/COBAS(®) TaqMan(®) v2.0 assay (HPS; LLOQ 25 IU/ml and LOD 15 IU/ml; Roche Diagnostics, Indianapolis, IN, USA) and reanalysed using Abbott realtime assay (ART; LLOQ and LOD 12 IU/ml; Abbott Molecular Inc., Des Plaines, IL, USA).
  
  
  RESULTS
  Overall, 217/766 (28.3%) samples from different time points with HCV RNA undetectable by HPS had HCV RNA detectable by ART. Conversely, 35/584 (6.0%) samples undetectable by ART were detectable by HPS. For both assays, most discrepant samples (96-100%) had HCV RNA<25 IU/ml. At week 4, 75.5% of samples were undetectable by HPS, whereas 49.4% were undetectable by ART, resulting in different RGT assessment in 26.1% (P<0.0001). At week 12, 95.4% and 91.9% of samples were undetectable with HPS and ART, respectively.
  
  
  CONCLUSIONS
  Lower rates of undetectable HCV RNA with ART at week 4 suggest that if RGT criteria are determined with ART, the proportion of patients qualifying for shorter treatment duration may be significantly lower (26%). Therefore, different RGT criteria may be necessary for ART to maximize numbers benefiting from shortened treatment. Further testing and validation are required.
authors.affiliation: Janssen Infectious Disease BVBA, Beerse, Belgium.
authors.forename: Bart
authors.initials: B
authors.lastname: Fevery
authors.forename: Simone
authors.initials: S
authors.lastname: Susser
authors.forename: Oliver
authors.initials: O
authors.lastname: Lenz
authors.forename: Gavin
authors.initials: G
authors.lastname: Cloherty
authors.forename: Dany
authors.initials: D
authors.lastname: Perner
authors.forename: Gaston
authors.initials: G
authors.lastname: Picchio
authors.forename: Christoph
authors.initials: C
authors.lastname: Sarrazin
mesh_terms: D000998:Antiviral Agents / Q000627:therapeutic use; D016174:Hepacivirus / Q000235:genetics*; D006526:Hepatitis C / Q000175:diagnosis* / Q000188:drug therapy / Q000821:virology*; D006801:Humans; D011480:Protease Inhibitors / Q000627:therapeutic use; D012367:RNA, Viral; D011933:Reagent Kits, Diagnostic; D060888:Real-Time Polymerase Chain Reaction / Q000379:methods / Q000592:standards; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013997:Time Factors; D016896:Treatment Outcome; D019562:Viral Load / Q000379:methods* / Q000592:standards
chemical_list: D000998:Antiviral Agents; D011480:Protease Inhibitors; D012367:RNA, Viral; D011933:Reagent Kits, Diagnostic