Role of NS5A-L31/Y93 double wild-type in failure of glecaprevir/pibrentasvir double therapy in two patients with a history of direct-acting antiviral agent failure: An ultra-deep sequencing analysis

Abstract

We experienced two cases of hepatitis C virus (HCV) eradication failure in patients with a history of nonresponsiveness to previous treatments with direct-acting antiviral agents (DAAs) who were subsequently treated with the combination of glecaprevir and pibrentasvir (GLE/PIB). Direct sequencing at commencement of GLE/PIB therapy showed non-structural protein (NS) 5A-P32 deletion in the first patient and NS5AR30E/Q54H/A92K in the second patient (both genotype 1b). The common point was that L31/Y93 was double wild-type, and the IL28B polymorphism was non-TT type. Even when L31/Y93 is double wild-type, other NS5A mutations may affect the DAA re-treatment outcome. We analyzed the transition of amino acid mutations at NS5A by ultra-deep sequencing.