論文

査読有り
2016年

Low frequency of drug-resistant virus did not affect the therapeutic efficacy in daclatasvir plus asunaprevir therapy in patients with chronic HCV genotype-1 infection

ANTIVIRAL THERAPY
  • Hideaki Kinugasa
  • ,
  • Fusao Ikeda
  • ,
  • Kouichi Takaguchi
  • ,
  • Chizuru Mori
  • ,
  • Takehiro Matsubara
  • ,
  • Hidenori Shiraha
  • ,
  • Akinobu Takaki
  • ,
  • Yoshiaki Iwasaki
  • ,
  • Shinichi Toyooka
  • ,
  • Kazuhide Yamamoto

21
1
開始ページ
37
終了ページ
44
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.3851/IMP2976
出版者・発行元
INT MEDICAL PRESS LTD

Background: The efficacy of a direct-acting antiviral agent (DAA) is compromised by the development of drug resistance. The associations between resistance-associated virus (RAV) and therapeutic outcomes have not been well-understood.
Methods: A total of 30 patients with HCV genotype-1b were enrolled and treated for 24 weeks with asunaprevir (ASV) and daclatasvir (DCV). Viral sequences in non-structural (NS) regions 3 and 5A in serum and liver tissue before treatment were examined with direct sequencing, next-generation sequencing (NGS) and the PCR-invader method to evaluate the importance of drug-resistance in the prediction of the outcomes of ASV plus DCV therapy.
Results: Of 30 patients (22 treatment-naive patients, 2 interferon-intolerant patients and 6 non-responders), 25 patients (83.3%) achieved sustained virological response (SVR) 24 weeks after the treatment. Viral breakthrough occurred in three treatment-naive patients and one non-responder. One treatment-naive patient experienced viral relapse. Among 25 patients without RAV, 24 obtained SVR, whereas 5 patients had RAV with a 1.3 to 88% frequency, resulting in various therapeutic outcomes. As for HCV compartments, similar RAVs were detected in serum and liver tissue for a patient obtaining SVR despite HCV NS5A Y93H and another developed viral breakthrough although no RAV was detected. Direct sequencing could not detect RAVs in low frequency (1.3 to 12%) for three of four patients.
Conclusions: Low frequency of RAVs might not affect the outcomes of ASV plus DCV therapy. Deep sequencing and PCR-invader methods can detect clinically significant RAVs for ASV plus DCV therapy.

Web of Science ® 被引用回数 : 14

リンク情報
DOI
https://doi.org/10.3851/IMP2976
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/26115551
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000389744300005&DestApp=WOS_CPL
ID情報
  • DOI : 10.3851/IMP2976
  • ISSN : 1359-6535
  • PubMed ID : 26115551
  • Web of Science ID : WOS:000389744300005

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