Comparison of on-treatment HCV RNA during direct antiviral therapy using two different COBAS TaqMan HCV assays

- On-treatment HCV RNA monitoring may be useful in difficult-to-treat patients who receive DAA-based therapies.
- Most DAA approval studies used the HPS/CTM assay for HCV RNA testing, whereas the CAP/CTM assay is more widely used in clinical practice.
- We observed different HCV RNA kinetics with the two assays in our study.
- HCV RNA was below the limit of quantification according to both assays at treatment week 8.
- On-treatment HCV RNA was not predictive of SVR with either assay.

BackgroundRepeated measurements of hepatitis C virus (HCV) RNA levels during antiviral therapy are recommended to monitor treatment efficacy and adherence. Throughout most direct antiviral agent (DAA) approval studies, HCV RNA cutoffs and endpoints were established with the COBAS TaqMan assay for use with the High Pure System (HPS/CTM). Different assays used in clinical practice may yield different quantitative results and possibly impact treatment decisions.ObjectivesThe concordance of the fully-automated COBAS AmpliPrep/COBAS TaqMan assay (CAP/CTM) with HPS/CTM and its ability to predict response to DAA-treatment with ledipasvir/sofosbuvir was assessed in cirrhotic patients with HCV genotype-1-infection who had failed prior treatment with protease inhibitor-based regimens.Study designSerum samples from patients (n = 154) treated in the phase-2 SIRIUS-study were collected at baseline and during antiviral therapy (weeks 1-8), and were tested in parallel by both assays.ResultsThe mean difference between HPS/CTM and CAP/CTM at baseline (n = 153) was 0.32 log10 IU/mL HCV RNA. Discordant results were observed in 12% of samples collected at treatment weeks 1-8, with the greatest differences observed at weeks 2 and 4 (14% and 29%, respectively, for undetectable HCV RNA). SVR rates were 96%-97% in the study and were not significantly different between patients with detectable vs. undetectable HCV RNA according to both assays at weeks 1-4 of antiviral therapy.ConclusionsCAP/CTM and HPS/CTM showed significantly different response rates during the early stages of ledipasvir/sofosbuvir treatment. However, on-treatment response was not predictive of SVR with either assay, indicating that determination of on-treatment HCV RNA levels may not be useful to guide treatment decisions.