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

Smith, D. A. et al. (2021) Real world SOF/VEL/VOX retreatment outcomes and viral resistance analysis for HCV patients with prior failure to DAA therapy. Journal of Viral Hepatitis, 28(9), pp. 1256-1264. (doi: 10.1111/jvh.13549) (PMID:34003556)

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.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Thomson, Professor Emma and Aranday-Cortes, Dr Elihu and Da Silva Filipe, Dr Ana and McLauchlan, Professor John and Singer, Dr Josh
• Authors: Smith, D. A., Bradshaw, D., Mbisa, J. L., Manso, C. F., Bibby, D. F., Singer, J. B., Thomson, E. C., da Silva Filipe, A., Aranday-Cortes, E., Ansari, M. A., Brown, A., Hudson, E., Benselin, J., Healy, B., Troke, P., McLauchlan, J., Barnes, E., and Irving, W. L.
• College/School: College of Medical Veterinary and Life Sciences > School of Infection & Immunity > Centre for Virus Research
• Journal Name: Journal of Viral Hepatitis
• Publisher: Wiley
• ISSN: 1352-0504
• ISSN (Online): 1365-2893
• Published Online: 18 May 2021
• Copyright Holders: Copyright © 2021 Crown copyright
• First Published: First published in Journal of Viral Hepatitis 28(9): 1256-1264
• Publisher Policy: Reproduced under a Creative Commons License