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Title: Prevalence of end of treatment RNA-positive/sustained viral response in HCV patients treated with sofosbuvir combination therapies

Abstract

Background: Some chronic hepatitis C virus (HCV), genotype 1 infected patients treated with direct antiviral agents (DAAs) remain viremic at end of treatment (EOT+), yet go on to achieve sustained virological response 12 weeks after completion of therapy (SVR 12). The incidence of EOT+/SVR in patients with genotype 1 and other genotypes, as well as whether such patients achieve SVR 24 remain in question. The aims of this study were to evaluate the frequency and durability of EOT+/SVR 12&24 and other response categories in HCV genotype 1, 2, or 3 infected patients treated with DAA in clinical practice. Methods: Data from patients treated with all oral sofosbuvir-based regimens at a university hepatology practice by 1 July 2015 were reviewed retrospectively. Responses were categorized based on virus levels during and post DAA treatment. HCV RNA levels were measured by Abbott RealTime HCV (ART) or by Roche CobasTaqMan v2.0 (RCTM) assays. Results: The study population included 89 patients. Participants were 62% genotype 1, 19% genotype 2 and 19% genotype 3, 54% cirrhotic and 46% treatment-experienced. A total of 45 received sofosbuvir-simeprevir, 38 sofosbuvir-ribavirin and 6 sofosbuvir-ledipasvir. The SVR12 rate was 82%. A total of 5 patients (6%), all with genotype 1, hadmore » EOT+ by ART assay and each achieved SVR 12&24. Conclusions: A total of 9% of genotype 1 patients (6% overall) treated with DAAs were EOT+ by ART and all EOT+ cases achieved SVR 24. EOT+/SVR was not observed with genotype 2 or 3 or by the RCTM assay. In patients treated with DAAs, EOT+ by the ART assay does not indicate treatment failure.« less

Authors:
 [1];  [2];  [2];  [3];  [2];  [2]
  1. Division of Gastroenterology and Hepatology, Department of Medicine, University of Florida Health, 4555 Emerson St. Ste. 300, Jacksonville, FL 32207, USA
  2. Program for Experimental and Theoretical Modeling, Division of Hepatology, Department of Medicine, Loyola University Medical Center, Maywood, IL, USA
  3. Theoretical Biology and Biophysics Group, Los Alamos National Laboratory, Los Alamos, NM, USA
Publication Date:
Research Org.:
Los Alamos National Lab. (LANL), Los Alamos, NM (United States)
Sponsoring Org.:
USDOE; National Institutes of Health (NIH)
OSTI Identifier:
1626246
Grant/Contract Number:  
AC52-06NA25396; R01-AI078881; R01-OD011095; P20-GM10 3452
Resource Type:
Journal Article: Accepted Manuscript
Journal Name:
Therapeutic Advances in Gastroenterology
Additional Journal Information:
Journal Volume: 10; Journal Issue: 1; Journal ID: ISSN 1756-283X
Publisher:
SAGE Publishing
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; Gastroenterology & Hepatology; HCV; SVR; direct antiviral agents; end of treatment response

Citation Formats

Malespin, Miguel, Benyashvili, Tamara, Uprichard, Susan L., Perelson, Alan S., Dahari, Harel, and Cotler, Scott J. Prevalence of end of treatment RNA-positive/sustained viral response in HCV patients treated with sofosbuvir combination therapies. United States: N. p., 2016. Web. doi:10.1177/1756283x16672392.
Malespin, Miguel, Benyashvili, Tamara, Uprichard, Susan L., Perelson, Alan S., Dahari, Harel, & Cotler, Scott J. Prevalence of end of treatment RNA-positive/sustained viral response in HCV patients treated with sofosbuvir combination therapies. United States. doi:10.1177/1756283x16672392.
Malespin, Miguel, Benyashvili, Tamara, Uprichard, Susan L., Perelson, Alan S., Dahari, Harel, and Cotler, Scott J. Mon . "Prevalence of end of treatment RNA-positive/sustained viral response in HCV patients treated with sofosbuvir combination therapies". United States. doi:10.1177/1756283x16672392. https://www.osti.gov/servlets/purl/1626246.
@article{osti_1626246,
title = {Prevalence of end of treatment RNA-positive/sustained viral response in HCV patients treated with sofosbuvir combination therapies},
author = {Malespin, Miguel and Benyashvili, Tamara and Uprichard, Susan L. and Perelson, Alan S. and Dahari, Harel and Cotler, Scott J.},
abstractNote = {Background: Some chronic hepatitis C virus (HCV), genotype 1 infected patients treated with direct antiviral agents (DAAs) remain viremic at end of treatment (EOT+), yet go on to achieve sustained virological response 12 weeks after completion of therapy (SVR12). The incidence of EOT+/SVR in patients with genotype 1 and other genotypes, as well as whether such patients achieve SVR24 remain in question. The aims of this study were to evaluate the frequency and durability of EOT+/SVR12&24 and other response categories in HCV genotype 1, 2, or 3 infected patients treated with DAA in clinical practice. Methods: Data from patients treated with all oral sofosbuvir-based regimens at a university hepatology practice by 1 July 2015 were reviewed retrospectively. Responses were categorized based on virus levels during and post DAA treatment. HCV RNA levels were measured by Abbott RealTime HCV (ART) or by Roche CobasTaqMan v2.0 (RCTM) assays. Results: The study population included 89 patients. Participants were 62% genotype 1, 19% genotype 2 and 19% genotype 3, 54% cirrhotic and 46% treatment-experienced. A total of 45 received sofosbuvir-simeprevir, 38 sofosbuvir-ribavirin and 6 sofosbuvir-ledipasvir. The SVR12 rate was 82%. A total of 5 patients (6%), all with genotype 1, had EOT+ by ART assay and each achieved SVR12&24. Conclusions: A total of 9% of genotype 1 patients (6% overall) treated with DAAs were EOT+ by ART and all EOT+ cases achieved SVR24. EOT+/SVR was not observed with genotype 2 or 3 or by the RCTM assay. In patients treated with DAAs, EOT+ by the ART assay does not indicate treatment failure.},
doi = {10.1177/1756283x16672392},
journal = {Therapeutic Advances in Gastroenterology},
issn = {1756-283X},
number = 1,
volume = 10,
place = {United States},
year = {2016},
month = {10}
}

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