Significance of detectable HCV RNA below the limit of quantification in patients treated with DAAs using standard and ultrasensitive protocols

J Med Virol. 2018 Jul;90(7):1264-1271. doi: 10.1002/jmv.25084. Epub 2018 Apr 26.

Abstract

Predictive factors of HCV relapse after treatment with DAAs are poorly understood. In this study, we aimed to assess whether the residual viral load positivity observed during or at the end of treatment (EOT) has an impact on viral outcome. Blood samples were collected from 337 patients with genotypes (GT) 1a, 1b, 2, 3, and 4 HCV chronic infection, treated with DAAs to determine HCV RNA load by the Abbott RealTime HCV (ART) assay at treatment week (W) 4, at EOT, and 4, 12, 24 weeks after discontinuation. EOT and other samples with "detected <12/mL" (DNQ) were retested by an ultrasensitive protocol (USP) to confirm the result. Frequency of DNQ was analyzed in subgroups of patients and clinical conditions to assess potential correlations. At W4, 22% and 30.9% of the samples were undetectable and DNQ by ART assay, respectively, but no correlation for achieving SVR was found. In contrast, an HCV RNA cut-off of ≥50/mL at W4 was a significant predictor of therapy failure (P = 0.036, univariate analysis). At EOT, DNQ was associated to 12W treatment duration (P < 0.001) and GT1a infection (P = 0.036). Overall, 20/41 (48.8%) of DNQ samples at EOT or post-treatment W4, were confirmed by USP but only in a single case the patient experienced viral relapse. HCV RNA at W4 can predict SVR, irrespective to genotype or DAA regimen. HCV RNA DNQ at EOT is associated to shorter treatment duration and to GT1a, but is not a predictor of therapy failure.

Keywords: HCV direct-acting antiviral agents; end of treatment residual viral load; on treatment response predictors; ultra sensitive HCV quantification.

Publication types

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

MeSH terms

  • Drug Monitoring
  • Female
  • Hepacivirus / isolation & purification*
  • Hepatitis C, Chronic / drug therapy*
  • Hepatitis C, Chronic / virology*
  • Humans
  • Male
  • RNA, Viral / blood*
  • Recurrence
  • Retrospective Studies
  • Sustained Virologic Response*
  • Treatment Outcome
  • Viral Load*

Substances

  • RNA, Viral