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

J Clin Virol. 2015 Nov:72:133-40. doi: 10.1016/j.jcv.2015.09.015. Epub 2015 Oct 8.

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.

Objectives: 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.

Study design: 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.

Keywords: Assay concordance; DAA; HCV RNA quantification; HCV genotype 1 and 4; Response-guided treatment; Simeprevir.

Publication types

  • Comparative Study
  • Evaluation Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antiviral Agents / administration & dosage*
  • Clinical Trials, Phase III as Topic
  • Drug Monitoring / methods*
  • Genotype
  • Hepacivirus / classification
  • Hepacivirus / genetics
  • Hepacivirus / isolation & purification*
  • Hepatitis C, Chronic / drug therapy*
  • Hepatitis C, Chronic / virology*
  • Humans
  • Interferon-alpha / administration & dosage
  • Protease Inhibitors
  • RNA, Viral / blood*
  • Retrospective Studies
  • Ribavirin / administration & dosage
  • Simeprevir / administration & dosage
  • Viral Load / methods*

Substances

  • Antiviral Agents
  • Interferon-alpha
  • Protease Inhibitors
  • RNA, Viral
  • Ribavirin
  • Simeprevir