Johannes Vermehren1, Marc Bourlière2, Stanislas Pol3, Patrick Marcellin4, Robert H Hyland5, Deyuan Jiang5, Diana M Brainard5, Stefan Zeuzem6, Tania M Welzel7. 1. Medizinische Klinik 1, Universitätsklinikum Frankfurt, Frankfurt am Main, Germany. Electronic address: johannes.vermehren@kgu.de. 2. Hépato-Gastroénterologie, Hôpital-Saint Joseph, Marseille, France. 3. Hépatologie, Université Paris Descartes, Inserm UMS20, Institut Pasteur, Hôpital Cochin, France. 4. Service d'Hepatologie, Hôpital Beaujon, Clichy, France. 5. Liver Disease Therapeutic Area, Gilead Sciences, Foster City, CA, USA. 6. Medizinische Klinik 1, Universitätsklinikum Frankfurt, Frankfurt am Main, Germany. 7. Medizinische Klinik 1, Universitätsklinikum Frankfurt, Frankfurt am Main, Germany. Electronic address: tania.welzel@kgu.de.
Abstract
BACKGROUND: Repeated 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. OBJECTIVES: The 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 DESIGN: Serum 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. RESULTS: The 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. CONCLUSIONS: CAP/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.
BACKGROUND: Repeated 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. OBJECTIVES: The 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 DESIGN: Serum 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. RESULTS: The 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. CONCLUSIONS:CAP/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.
Keywords:
COBAS AmpliPrep/COBAS TaqMan HCV test v2.0; COBAS TaqMan HCV test v2.0 for use with the High Pure System; HCV RNA quantification; Hepatitis C virus; Ledipasvir/sofosbuvir; direct acting antiviral agents
Authors: Marcus M Mücke; Benjamin Maasoumy; Julia Dietz; Victoria T Mücke; Christian O Simon; Jesse A Canchola; Marcus Cornberg; Ed G Marins; Michael P Manns; Stefan Zeuzem; Heiner Wedemeyer; Christoph Sarrazin; Johannes Vermehren Journal: PLoS One Date: 2019-11-18 Impact factor: 3.240
Authors: Michael J Zoratti; Ayesha Siddiqua; Rita E Morassut; Dena Zeraatkar; Roger Chou; Judith van Holten; Feng Xie; Eric Druyts Journal: EClinicalMedicine Date: 2020-01-05