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Efficacy of 12 or 18 weeks of elbasvir plus grazoprevir with ribavirin in treatment-naïve, noncirrhotic HCV genotype 3-infected patients.
- Source :
-
Journal of viral hepatitis [J Viral Hepat] 2017 Oct; Vol. 24 (10), pp. 895-899. Date of Electronic Publication: 2017 Jun 23. - Publication Year :
- 2017
-
Abstract
- Elbasvir (EBR; HCV NS5A inhibitor) and grazoprevir (GZR; HCV NS3/4A protease inhibitor) are approved as a fixed-dose combination to treat patients chronically infected with HCV genotypes 1 and 4. During the development programme and supported by in vitro potency, the efficacy of EBR+GZR was assessed in HCV GT3-infected patients. This study's aim was to determine the efficacy and tolerability of 12 or 18 weeks of EBR+GZR with ribavirin (RBV) in treatment-naïve, noncirrhotic HCV GT3-infected patients. Randomized patients received open-label EBR (50 mg once daily) + GZR (100 mg once daily) + RBV. The primary efficacy objective was to evaluate the sustained virologic response rates 12 weeks after the end of all study therapy (SVR12). SVR12 rates (95% confidence interval) were 45.0% (23.1, 68.5) and 57.1% (34.0, 78.2) after treatment with EBR+GZR+RBV for 12 weeks or 18 weeks, respectively. On-treatment virologic failure was observed in 41% (17 of 41) of patients. At virologic failure, resistance-associated substitutions (RASs) with a >five-fold shift in potency occurred in the NS3 region in six (35%) patients and in the NS5A region in 16 (94%) patients. The most common RAS at virologic failure was Y93H in NS5A which was identified in 13 of 17 (76%) patients. The efficacy of EBR+GZR+RBV was suboptimal in HCV GT3-infected patients due to a high rate of on-treatment virologic failure and treatment-emergent RASs which demonstrates an inadequate barrier to the development of GT3 resistance. However, rapid viral clearance demonstrated the antiviral activity of EBR+GZR+RBV in GT3-infected patients.clinicaltrials.gov: NCT01717326.<br /> (© 2017 John Wiley & Sons Ltd.)
- Subjects :
- Adult
Aged
Amides
Antiviral Agents administration & dosage
Antiviral Agents adverse effects
Benzofurans administration & dosage
Benzofurans adverse effects
Carbamates
Cyclopropanes
Drug Resistance, Viral
Drug Therapy, Combination
Female
Hepacivirus drug effects
Humans
Imidazoles administration & dosage
Imidazoles adverse effects
Male
Microbial Sensitivity Tests
Middle Aged
Mutation
Quinoxalines administration & dosage
Quinoxalines adverse effects
RNA, Viral
Ribavirin administration & dosage
Ribavirin adverse effects
Sulfonamides
Time Factors
Treatment Failure
Treatment Outcome
Viral Load
Antiviral Agents therapeutic use
Benzofurans therapeutic use
Genotype
Hepacivirus genetics
Hepatitis C drug therapy
Hepatitis C virology
Imidazoles therapeutic use
Quinoxalines therapeutic use
Ribavirin therapeutic use
Subjects
Details
- Language :
- English
- ISSN :
- 1365-2893
- Volume :
- 24
- Issue :
- 10
- Database :
- MEDLINE
- Journal :
- Journal of viral hepatitis
- Publication Type :
- Academic Journal
- Accession number :
- 28470815
- Full Text :
- https://doi.org/10.1111/jvh.12719