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Real world SOF/VEL/VOX retreatment outcomes and viral resistance analysis for HCV patients with prior failure to DAA therapy
Author(s) -
Smith David A.,
Bradshaw Daniel,
Mbisa Jean L,
Manso Carmen F.,
Bibby David F,
Singer Joshua B,
Thomson Emma C,
da Silva Filipe Ana,
ArandayCortes Elihu,
Ansari M. Azim,
Brown Anthony,
Hudson Emma,
Benselin Jennifer,
Healy Brendan,
Troke Phil,
McLauchlan John,
Barnes Eleanor,
Irving William L.
Publication year - 2021
Publication title -
journal of viral hepatitis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.329
H-Index - 100
eISSN - 1365-2893
pISSN - 1352-0504
DOI - 10.1111/jvh.13549
Subject(s) - medicine , sofosbuvir , hepatocellular carcinoma , hepatitis c virus , cohort , gastroenterology , univariate analysis , cirrhosis , hepatitis c , ribavirin , virus , virology , multivariate analysis
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.