GT-1a or GT-1b subtype-specific resistance profiles for hepatitis C virus inhibitors telaprevir and HCV-796.
In vitro, telaprevir selects subtype-specific resistance pathways for hepatitis C virus GT-1a and GT-1b, as described to have occurred in patients. In GT-1a, the HCV-796 resistance mutation C316Y has low replication capacity (7%) that can be compensated for by the emergence of the mutation L392F or M414T, resulting in an increase in replication levels of > or = 10-fold.
McCown
Matthew F
MF
Roche Palo Alto LLC, 3431 Hillview Ave., Palo Alto, CA 94304, USA.
Rajyaguru
Sonal
S
Kular
Simran
S
Cammack
Nick
N
Nájera
Isabel
I
D000998:Antiviral Agents / Q000494:pharmacology / Q000627:therapeutic use; D001572:Benzofurans / Q000494:pharmacology / Q000627:therapeutic use; D024882:Drug Resistance, Viral / Q000235:genetics; D005838:Genotype; D016174:Hepacivirus / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics* / Q000502:physiology; D006801:Humans; D007700:Kinetics; D008826:Microbial Sensitivity Tests; D009842:Oligopeptides / Q000494:pharmacology / Q000627:therapeutic use; D011480:Protease Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D013449:Sulfonamides / Q000494:pharmacology / Q000627:therapeutic use; D017361:Viral Nonstructural Proteins / Q000235:genetics; D014779:Virus Replication / Q000187:drug effects; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases; D012324:RNA-Dependent RNA Polymerase
D000998:Antiviral Agents; D001572:Benzofurans; D009842:Oligopeptides; D011480:Protease Inhibitors; D013449:Sulfonamides; D017361:Viral Nonstructural Proteins; C539481:HCV 796; C084422:NS3 protein, hepatitis C virus; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases; C486464:telaprevir; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase