Real world SOF/VEL/VOX retreatment outcomes and viral resistance analysis for HCV patients with prior failure to DAA therapy

David A. Smith, Daniel Bradshaw*, Jean L. Mbisa, Carmen F. Manso, David F. Bibby, Joshua B. Singer, Emma C. Thomson, Ana da Silva Filipe, Elihu Aranday-Cortes, M. Azim Ansari, Anthony Brown, Emma Hudson, Jennifer Benselin, Brendan Healy, Phil Troke, John McLauchlan, Eleanor Barnes, William L. Irving

*Corresponding author for this work

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19 Citations (Scopus)
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Abstract

Sustained viral response (SVR) rates for direct-acting antiviral (DAA) therapy for hepatitis C virus (HCV) infection routinely exceed 95%. However, a small number of patients require retreatment. Sofosbuvir, velpatasvir and voxilaprevir (SOF/VEL/VOX) is a potent DAA combination primarily used for the retreatment of patients who failed by DAA therapies. Here we evaluate retreatment outcomes and the effects of resistance-associated substitutions (RAS) in a real-world cohort, including a large number of genotype (GT)3 infected patients. 144 patients from the UK were retreated with SOF/VEL/VOX following virologic failure with first-line DAA treatment regimens. Full-length HCV genome sequencing was performed prior to retreatment with SOF/VEL/VOX. HCV subtypes were assigned and RAS relevant to each genotype were identified. GT1a and GT3a each made up 38% (GT1a n = 55, GT3a n = 54) of the cohort. 40% (n = 58) of patients had liver cirrhosis of whom 7% (n = 4) were decompensated, 10% (n = 14) had hepatocellular carcinoma (HCC) and 8% (n = 12) had received a liver transplant prior to retreatment. The overall retreatment SVR12 rate was 90% (129/144). On univariate analysis, GT3 infection (50/62; SVR = 81%, p =.009), cirrhosis (47/58; SVR = 81%, p =.01) and prior treatment with SOF/VEL (12/17; SVR = 71%, p =.02) or SOF+DCV (14/19; SVR = 74%, p =.012) were significantly associated with retreatment failure, but existence of pre-retreatment RAS was not when viral genotype was taken into account. Retreatment with SOF/VEL/VOX is very successful for non-GT3-infected patients. However, for GT3-infected patients, particularly those with cirrhosis and failed by initial SOF/VEL treatment, SVR rates were significantly lower and alternative retreatment regimens should be considered.

Original languageEnglish
Pages (from-to)1256-1264
Number of pages9
JournalJournal of Viral Hepatitis
Volume28
Issue number9
Early online date18 May 2021
DOIs
Publication statusPublished - Sept 2021

Bibliographical note

Funding Information: The authors acknowledge Gilead Sciences for funding this study. The funder had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

DB has received research grant support from Gilead Sciences. WLI has received speaker and consultancy fees from Roche, Janssen Cilag, Gilead Sciences and Novartis, educational grants from Boehringer Ingelheim, Merck Sharp and Dohme and Gilead Sciences, and research grant support from GlaxoSmithKline, Pfizer, Gilead Sciences, Janssen Cilag, Abbvie and Bristol-Myers Squibb. The remaining authors have no conflicts of interest.

Open Access: This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Publisher Copyright: © 2021 Crown copyright. Journal of Viral Hepatitis published by John Wiley & Sons Ltd. This article is published with the permission of the Controller of HMSO and the Queen's Printer for Scotland.

Citation: Smith, DA, Bradshaw, D, Mbisa, J, et al. Real world SOF/VEL/VOX retreatment outcomes and viral resistance analysis for HCV patients with prior failure to DAA therapy. J Viral Hepat. 2021; 28: 1256– 1264.

DOI: https://doi.org/10.1111/jvh.13549

Keywords

  • direct-acting antivirals
  • hepatitis C virus
  • resistance-associated substitutions
  • retreatment

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