2018年8月
Limitations of daclatasvir/asunaprevir plus beclabuvir treatment in cases of NS5A inhibitor treatment failure
JOURNAL OF GENERAL VIROLOGY
- 巻
- 99
- 号
- 8
- 開始ページ
- 1058
- 終了ページ
- 1065
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.1099/jgv.0.001091
- 出版者・発行元
- MICROBIOLOGY SOC
Combined daclatasvir (DCV)/asunaprevir (ASV) plus beclabuvir (BCV) treatment shows a high virological response for genotype 1 b 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-nafve 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-naive-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-nafve 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-naNe 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.
- リンク情報
- ID情報
-
- DOI : 10.1099/jgv.0.001091
- ISSN : 0022-1317
- eISSN : 1465-2099
- Web of Science ID : WOS:000440461400011