1887

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Volume 99, Issue 8

Limitations of daclatasvir/asunaprevir plus beclabuvir treatment in cases of NS5A inhibitor treatment failure Free

Abstract

Combined daclatasvir (DCV)/asunaprevir (ASV) plus beclabuvir (BCV) treatment shows a high virological response for genotype 1b chronic hepatitis C patients. However, its efficacy for patients for whom previous direct-acting antiviral (DAA) therapy failed is not known. We analysed the efficacy of DCV/ASV/BCV treatment for HCV-infected mice and chronic hepatitis patients. Human hepatocyte chimaeric mice were injected with serum samples obtained from either a DAA-naïve patient or a DCV/ASV treatment failure and were then treated with DCV/ASV alone or in combination with BCV for 4 weeks. DCV/ASV treatment successfully eliminated the virus in DAA-naïve-patient HCV-infected mice. DCV/ASV treatment failure HCV-infected mice developed viral breakthrough during DCV/ASV treatment, with the emergence of NS5A-L31V/Y93H HCV resistance-associated variants (RAVs) being observed by direct sequencing. DCV/ASV/BCV treatment inhibited viral breakthrough in NS5A-L31V/Y93H-mutated HCV-infected mice, but HCV relapsed with the emergence of NS5B-P495S variants after the cessation of the treatment. The efficacy of the triple therapy was also analysed in HCV-infected patients; one DAA-naïve patient and four prior DAA treatment failures were treated with 12 weeks of DCV/ASV/BCV therapy. Sustained virological response was achieved in a DAA-naïve patient and one of the DCV/ASV treatment failures through DCV/ASV/BCV therapy; however, HCV relapse occurred in the other patients with prior DCV/ASV and/or sofosbuvir/ledipasvir treatment failures. DCV/ASV/BCV therapy seems to have limited efficacy for patients with NS5A RAVs for whom prior DAA treatment has failed.

  • Received:
  • Accepted:
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Keyword(s): asunaprevir , beclabuvir , daclatasvir , HCV , human hepatocyte chimeric mouse , RAV and treatment failures
© 2018 The Authors
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2018-06-19
2024-04-25
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Limitations of daclatasvir/asunaprevir plus beclabuvir treatment in cases of NS5A inhibitor treatment failure
J. Gen. Virol. 99, 1058 (2018); https://doi.org/10.1099/jgv.0.001091
/content/journal/jgv/10.1099/jgv.0.001091
/content/journal/jgv/10.1099/jgv.0.001091
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