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

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 and Tetsuo Takehara

PLOS ONE, 2020, vol. 15, issue 6, 1-12

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

Date: 2020
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Persistent link: https://EconPapers.repec.org/RePEc:plo:pone00:0234811

DOI: 10.1371/journal.pone.0234811

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