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AbstractSustained viral response (SVR) rates to first-line 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 first line DAA therapies. Here we evaluate retreatment outcomes and the effects of resistance associated substitutions (RAS) in a real-world cohort, including the largest number of genotype (GT)3 infected patients, to date. 144 patients from the UK were retreated with SOF/VEL/VOX following virologic failure with first-line DAA treatment regimens. Full-length HCV genome, next-generation sequencing was performed prior to retreatment with SOF/VEL/VOX. HCV subtypes were assigned and RAS relevant to each genotype were identified (15% read cut-off). GT1a and GT3a were the two most common subtypes in the cohort, each making 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 all significantly associated with retreatment failure, but existence of pre retreatment RAS was not when the genotype of the virus is taken into account. The lower SVR rates achieved in patients retreated with SOF/VEL/VOX for patients with GT3 infection, cirrhosis and prior treatment with SOF/VEL or SOF/DCV has important implications for both patients and HCV elimination strategies.

Original publication




Journal article


Cold Spring Harbor Laboratory

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