Real World SOF/VEL/VOX Retreatment Outcomes and Viral Resistance Analysis for HCV Patients with Prior Failure to DAA Therapy.

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.