Ultra‐deep sequencing analysis of resistance‐associated variants during retreatment with simeprevir‐based triple therapy after failure of telaprevir‐based triple therapy in patients with genotype 1 hepatitis C virus infection

Abstract

In this study, ultra-deep sequencing analysis revealed that TVR and/or SMV-resistant variants may have no influence on the effect of SMV-based therapy after failure of TVR-based therapy. Patients who discontinued treatment owing to adverse effects of TVR-based therapy and relapsers to previous pegylated interferon/ribavirin therapy would be good candidates for retreatment with SMV-based therapy.

Occurrence of late relapse of hepatitis C virus confirmed by molecular analysis after sustained virologic response to interferon–ribavirin‐based therapy

“…Most relapsers treated with PegIFN + ribavirin + simeprevir therapy acquired RAS such as D168E/V after treatment failure. 28,29 However, RAS in the NS3 region did not emerge in the patient who relapsed following PegIFN + ribavirin + simeprevir therapy. The mechanisms by which relapse and late relapse occur likely differ according to this emergence pattern of RAS.…”

“…Most relapsers treated with PegIFN + ribavirin + simeprevir therapy acquired RAS such as D168E/V after treatment failure . However, RAS in the NS3 region did not emerge in the patient who relapsed following PegIFN + ribavirin + simeprevir therapy.…”

A 3-year follow-up study after treatment with simeprevir in combination with pegylated interferon-α and ribavirin for chronic hepatitis C virus infection

“…The impact of persistence of treatment-emergent amino acid substitutions is not fully understood, and NS5A amino acid substitutions can persist for a long time [ 10 ]. However, data have shown that patients failing treatment with NS3 or NS5A inhibitors may be successfully re-treated with available regimens, even in the presence of amino acid substitutions [ 24 , 25 ]. Re-treatment strategies have recently been studied in Phase III trials.…”