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Abstract Details
Real World SOF/VEL/VOX Retreatment Outcomes and Viral Resistance Analysis for HCV Patients with Prior Failure to DAA Therapy
J Viral Hepat. 2021 May 18. doi: 10.1111/jvh.13549. Online ahead of print.
David A Smith12, Daniel Bradshaw3, Jean Mbisa3, Carmen F Manso3, David Bibby3, Josh Singer4, Emma Thomson4, Ana Filipe4, Elihu Aranday-Cortes4, M Azim Ansari1, Anthony Brown1, Emma Hudson1, Jennifer Benselin5, Brendan Healy6, Phil Troke7, John McLauchlan4, Eleanor Barnes12, William L Irving5
Author information
Affiliations collapse1Peter Medawar Building for Pathogen Research, Nuffield Department of Medicine, University of Oxford.
2NIHR Oxford Biomedical Research Centre.
3National Infection Service, Public Health England.
4MRC-University of Glasgow Centre for Virus Research, Glasgow, G61 1QH.
5NIHR Biomedical Research Centre (BRC), Nottingham University Hospitals NHS Trust, University of Nottingham, Nottingham, UK.
6Public Health Wales Microbiology Cardiff, University Hospital of Wales.
7Gilead Sciences Ltd, London, UK.
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 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 re-treatment SVR12 rate was 90% (129/144). On univariate analysis, GT3 infection (50/62; SVR=81%, p=0.009), cirrhosis (47/58; SVR=81% , p=0.01) and prior treatment with SOF/VEL(12/17; SVR=71%, p=0.02) or SOF+DCV (14/19; SVR=74%, p=0.012) 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.