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Emergence of hepatitis C virus NS5A L31V plus Y93H variant upon treatment failure of daclatasvir and asunaprevir is relatively resistant to ledipasvir and NS5B polymerase nucleotide inhibitor GS-558093 in human hepatocyte chimeric mice.
- Source :
-
Journal of Gastroenterology . Nov2015, Vol. 50 Issue 11, p1145-1151. 7p. 3 Charts, 2 Graphs. - Publication Year :
- 2015
-
Abstract
- <bold>Background: </bold>Resistance-associated variants (RAVs) emerge at multiple positions spanning hepatitis C virus (HCV) NS3/4A and NS5A regions upon failure of asunaprevir/daclatasvir combination therapy. It has not been determined whether the emergence of such RAVs have an impact on re-treatment by a combination of ledipasvir and sofosbuvir, a potent regimen for HCV genotype 1 infection.<bold>Methods: </bold>TK-NOG human hepatocyte chimeric mice were inoculated with sera from a patient with treatment failure of asunaprevir/daclatasvir therapy.<bold>Results: </bold>They developed persistent HCV infection with triple variants of NS3/4A D168V, NS5A L31V plus Y93H. Administration of ledipasvir/GS-558093 (a NS5B nucleotide analog) in these mice failed to achieve end-of-treatment response or sustained virologic response, which was in sharp contrast to the results in mice with wild-type virus infection. The administration of telaprevir/GS-558093 successfully achieved it in those mice.<bold>Conclusions: </bold>Treatment failure with asunaprevir/daclatasvir may limit further treatment options. This population may represent a growing unmet medical need. [ABSTRACT FROM AUTHOR]
- Subjects :
- *HEPATITIS C virus
*POLYMERASES
*LIVER cells
*ENZYME inhibitors
*DRUG resistance
*LABORATORY mice
*HYDROCARBONS
*ANTIVIRAL agents
*HETEROCYCLIC compounds
*IMIDAZOLES
*ISOQUINOLINE
*SULFONAMIDES
*ANIMAL experimentation
*COMBINATION drug therapy
*DRUG resistance in microorganisms
*EPITHELIAL cells
*HEPATITIS viruses
*TREATMENT effectiveness
*CHRONIC hepatitis C
*THERAPEUTICS
Subjects
Details
- Language :
- English
- ISSN :
- 09441174
- Volume :
- 50
- Issue :
- 11
- Database :
- Academic Search Index
- Journal :
- Journal of Gastroenterology
- Publication Type :
- Academic Journal
- Accession number :
- 110813343
- Full Text :
- https://doi.org/10.1007/s00535-015-1108-6