Detection of low HCV viraemia by repeated HCV RNA testing predicts treatment failure to triple therapy with telaprevir

Aliment Pharmacol Ther. 2014 Jan;39(1):85-92. doi: 10.1111/apt.12544. Epub 2013 Nov 10.

Abstract

Background: Early on-treatment virological response is one of the most important predictors for sustained virological response (SVR) to treatment of chronic hepatitis C virus (HCV) genotype 1 infection with triple therapy including HCV protease inhibitors (PI). Treatment duration (24 vs. 48 weeks) is based on HCV RNA results at weeks 4 and 12 of PI therapy when HCV RNA must be 'undetectable' to allow shorter therapy.

Aim: To analyse the reliability of HCV RNA measurements at key decision time points (weeks 4 and 12) and the predictive value of concordant or discordant assay results for SVR.

Methods: Weeks 4 and 12 samples of patients receiving telaprevir-containing triple therapy were initially tested with the AmpliPrep/COBAS-TaqMan_HCV-Test-v1.0 (limit of detection; LOD = 15IU/mL) and retested with the AmpliPrep/COBAS-TaqMan_HCV-Test-v2.0 (LOD = 15IU/mL) and the High_Pure/COBAS-TaqMan_HCV-Test-v2.0 (LOD = 20IU/mL).

Results: Concordance among the three test results in classifying samples as HCV RNA 'undetectable' or 'detectable' was only 55% at week 4, but 85% at week 12. Retesting of 'undetectable' week 4 samples with the respective other assays revealed positive HCV RNA results in 32-50%. In 30%, HCV RNA was 'undetectable' by all three tests at week 4 and all of these patients achieved SVR. In contrast, treatment failure occurred in 62% of patients with at least one 'detectable' result, including cases with one or two other 'undetectable' tests at week 4.

Conclusions: A single 'undetectable' HCV RNA result at week 4 is not always associated with achieving SVR. Repeated testing in difficult-to-treat patients may identify those at risk for treatment failure.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antiviral Agents / therapeutic use*
  • Drug Therapy, Combination
  • Hepacivirus / genetics*
  • Hepatitis C, Chronic / drug therapy*
  • Hepatitis C, Chronic / virology*
  • Humans
  • Interferon alpha-2
  • Interferon-alpha / therapeutic use
  • Middle Aged
  • Oligopeptides / therapeutic use
  • Polyethylene Glycols / therapeutic use
  • Protease Inhibitors / therapeutic use
  • RNA, Viral / analysis*
  • Recombinant Proteins / therapeutic use
  • Ribavirin / therapeutic use
  • Treatment Failure
  • Viremia / genetics

Substances

  • Antiviral Agents
  • Interferon alpha-2
  • Interferon-alpha
  • Oligopeptides
  • Protease Inhibitors
  • RNA, Viral
  • Recombinant Proteins
  • Polyethylene Glycols
  • Ribavirin
  • telaprevir
  • peginterferon alfa-2b
  • peginterferon alfa-2a