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Pre-existing minor variants with NS5A L31M/V-Y93H double substitution are closely linked to virologic failure with asunaprevir plus daclatasvir treatment for genotype 1b hepatitis C virus infection

Author

Listed:
  • Naoki Morishita
  • Ryotaro Sakamori
  • Tomomi Yamada
  • Yugo Kai
  • Yuki Tahata
  • Ayako Urabe
  • Ryoko Yamada
  • Takahiro Kodama
  • Hayato Hikita
  • Yoshinori Doi
  • Shinji Tamura
  • Hideki Hagiwara
  • Yasuharu Imai
  • Sadaharu Iio
  • Tomohide Tatsumi
  • Tetsuo Takehara

Abstract

Background: L31 and Y93 in the NS5A region of the hepatitis C virus (HCV) are the most important substitution positions associated with resistance to direct-acting antiviral (DAA) treatment. Methods: We analyzed the frequency of NS5A L31M/V and Y93/H in NS5A inhibitor-naive HCV genotype 1 patients who received asunaprevir plus daclatasvir combination treatment using a conventional sequencing method and a deep sequencing method that can distinguish a single substitution at either position and a double substitution at both positions with a 0.1% detection threshold. Results: The frequency of substitutions at both sites using the conventional method was very low, with 1 in 14 non-responders and 0 in 42 randomly selected responder patients. On the other hand, for the deep sequencing method, cases with double substitutions in the tandem sequence were detected in 8/14 non-responders and 1/42 responders (p

Suggested Citation

  • Naoki Morishita & Ryotaro Sakamori & Tomomi Yamada & Yugo Kai & Yuki Tahata & Ayako Urabe & Ryoko Yamada & Takahiro Kodama & Hayato Hikita & Yoshinori Doi & Shinji Tamura & Hideki Hagiwara & Yasuharu , 2020. "Pre-existing minor variants with NS5A L31M/V-Y93H double substitution are closely linked to virologic failure with asunaprevir plus daclatasvir treatment for genotype 1b hepatitis C virus infection," PLOS ONE, Public Library of Science, vol. 15(6), pages 1-12, June.
    • Handle: RePEc:plo:pone00:0234811
    DOI: 10.1371/journal.pone.0234811
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