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.
Highlights
Sustained virological response (SVR) rates for patients chronically infected with hepatitis C virus (HCV) and treated with direct-acting antiviral (DAA) therapies in clinical trials and real-world cohorts are often >95%.1-3 Treatment failure is associated with multiple host and viral factors including advanced fibrosis or cirrhosis, HCV subtype4-6 and the presence of resistance-associated substitutions (RAS) in HCV-encoded proteins that are targeted by DAA.[7]
Our results show that retreatment of patients with SOF/VEL/VOX who have been failed by first-line therapy is very effective for GTs 1–3 (GT1)
Our data shows that GT3-infected patients achieved lower SVR rates to SOF/VEL/VOX retreatment; the lowest SVR12 rates (42%) were observed in patients with GT3 infection, cirrhosis and prior SOF/VEL exposure
Summary
Sustained virological response (SVR) rates for patients chronically infected with hepatitis C virus (HCV) and treated with direct-acting antiviral (DAA) therapies in clinical trials and real-world cohorts are often >95%.1-3 Treatment failure is associated with multiple host and viral factors including advanced fibrosis or cirrhosis, HCV subtype4-6 and the presence of resistance-associated substitutions (RAS) in HCV-encoded proteins that are targeted by DAA.[7]. For patients who have been failed by pan-genotypic regimens such as SOF/VEL and glecaprevir and pibrentasvir, (GLE/PIB) retreatment options are limited. SVR rates were significantly lower in patients with cirrhosis (89%, p = .05), or those with GT3 infection (80%, p < .001), whilst patients with GT3 infection and cirrhosis had the lowest SVR rate (69%) Despite these studies there remains limited data on SOF/ VEL/VOX retreatment from the real-world setting, for patients with GT3 infection following unsuccessful therapy with pan-genotypic DAA regimens. These data are required to inform optimal retreatment strategies. We report the outcomes of 144 patients failed by first-line DAA therapy and retreated with SOF/VEL/VOX. We analyse the effect of clinical characteristics and RAS on SOF/VEL/VOX retreatment
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