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

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. We analyzed the frequency of NS5A L31M/V and Y93/H in NS5A inhibitor-naive HCV genotype 1 patients who received asunaprev...

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Bibliographic Details
Published in:PloS one 2020-06, Vol.15 (6), p.e0234811-e0234811
Main Authors: Morishita, Naoki, Sakamori, Ryotaro, Yamada, Tomomi, Kai, Yugo, Tahata, Yuki, Urabe, Ayako, Yamada, Ryoko, Kodama, Takahiro, Hikita, Hayato, Doi, Yoshinori, Tamura, Shinji, Hagiwara, Hideki, Imai, Yasuharu, Iio, Sadaharu, Tatsumi, Tomohide, Takehara, Tetsuo
Format: Article
Language:English
Subjects:
Aged
Antiviral agents
Antiviral Agents - therapeutic use
Antiviral drugs
Biology and life sciences
Carbamates
Case-Control Studies
Disease resistance
Drug dosages
Drug resistance
Drug Resistance, Viral - genetics
Drug therapy
Drug Therapy, Combination
Female
Frequency analysis
Gastroenterology
Gene mutation
Genetic aspects
Genotype
Genotype & phenotype
Genotypes
Health aspects
Hepacivirus - genetics
Hepacivirus - isolation & purification
Hepatitis
Hepatitis C
Hepatitis C - drug therapy
Hepatitis C - virology
Hepatitis C virus
Hepatology
Hospitals
Humans
Identification and classification
Imidazoles - therapeutic use
Infections
Inhibitors
Isoquinolines - therapeutic use
Liver cancer
Liver diseases
Male
Medicine
Medicine and health sciences
Methods
Mutation
Nucleotide sequence
Pyrrolidines
Research and Analysis Methods
Studies
Substitutes
Sulfonamides - therapeutic use
Sustained Virologic Response
Treatment Failure
Valine - analogs & derivatives
Viral Nonstructural Proteins - genetics
Viruses
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Summary: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. 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. 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
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0234811