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Evolution of simeprevir-resistant variants over time by ultra-deep sequencing in HCV genotype 1b.
- Source :
-
Journal of medical virology [J Med Virol] 2014 Aug; Vol. 86 (8), pp. 1314-22. Date of Electronic Publication: 2014 May 05. - Publication Year :
- 2014
-
Abstract
- Using ultra-deep sequencing technology, the present study was designed to investigate the evolution of simeprevir-resistant variants (amino acid substitutions of aa80, aa155, aa156, and aa168 positions in HCV NS3 region) over time. In Toranomon Hospital, 18 Japanese patients infected with HCV genotype 1b, received triple therapy of simeprevir/PEG-IFN/ribavirin (DRAGON or CONCERT study). Sustained virological response rate was 67%, and that was significantly higher in patients with IL28B rs8099917 TT than in those with non-TT. Six patients, who did not achieve sustained virological response, were tested for resistant variants by ultra-deep sequencing, at the baseline, at the time of re-elevation of viral loads, and at 96 weeks after the completion of treatment. Twelve of 18 resistant variants, detected at re-elevation of viral load, were de novo resistant variants. Ten of 12 de novo resistant variants become undetectable over time, and that five of seven resistant variants, detected at baseline, persisted over time. In one patient, variants of Q80R at baseline (0.3%) increased at 96-week after the cessation of treatment (10.2%), and de novo resistant variants of D168E (0.3%) also increased at 96-week after the cessation of treatment (9.7%). In conclusion, the present study indicates that the emergence of simeprevir-resistant variants after the start of treatment could not be predicted at baseline, and the majority of de novo resistant variants become undetectable over time. Further large-scale prospective studies should be performed to investigate the clinical utility in detecting simeprevir-resistant variants.<br /> (© 2014 Wiley Periodicals, Inc.)
- Subjects :
- Adult
Aged
Antiviral Agents pharmacology
Female
Genotype
Hepacivirus genetics
Hepacivirus isolation & purification
Hepatitis C virology
Heterocyclic Compounds, 3-Ring pharmacology
Humans
Interferon-alpha therapeutic use
Japan
Male
Middle Aged
Ribavirin therapeutic use
Simeprevir
Sulfonamides pharmacology
Treatment Failure
Viral Load
Young Adult
Antiviral Agents therapeutic use
Drug Resistance, Viral
Hepacivirus drug effects
Hepatitis C drug therapy
Heterocyclic Compounds, 3-Ring therapeutic use
High-Throughput Nucleotide Sequencing
RNA, Viral genetics
Sulfonamides therapeutic use
Subjects
Details
- Language :
- English
- ISSN :
- 1096-9071
- Volume :
- 86
- Issue :
- 8
- Database :
- MEDLINE
- Journal :
- Journal of medical virology
- Publication Type :
- Academic Journal
- Accession number :
- 24797623
- Full Text :
- https://doi.org/10.1002/jmv.23966