No correspondence between resistance mutations in the HCV-NS3 protease at baseline and early telaprevir-based triple therapy
| Autor: | Henrique Sérgio Moraes Coelho, Edson Rondinelli, Débora S. Faffe, Rosane Silva, Thayanna Araujo Capitanio, Bianca Catarina Azeredo Cabral, Cristiane A. Villela-Nogueira, Jennifer Fróes Cruz Lima, Luísa Hoffmann, Turán P. Ürményi |
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| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
medicine.medical_treatment
Drug resistance Biology Virus Genetic diversity Pathology and Forensic Medicine Telaprevir chemistry.chemical_compound Pegylated interferon Physiology (medical) medicine Protease inhibitor (pharmacology) Protease Ribavirin Standard treatment virus diseases Regular Article Virology digestive system diseases chemistry NGS HCV Molecular Medicine NS3 protease medicine.drug |
| Zdroj: | BBA Clinical |
| ISSN: | 2214-6474 |
| Popis: | Direct-acting antiviral (DAA)-based therapy is the new standard treatment for chronic hepatitis C virus (HCV) infection. However, protease inhibitor (PI)-resistant viral variants have been often described. This study aimed to examine HCV-NS3 protease variants at baseline and at 4 weeks under triple therapy. To this end, we analyzed the presence of variants in HCV-NS3 protease region from peripheral blood samples of 16 patients infected with HCV-1 at baseline and at 4 weeks of combined therapy with telaprevir, pegylated interferon, and ribavirin, using next-generation sequencing. Several variants with synonymous and non-synonymous amino acid substitutions were detected at both time points. Variants detected at low frequency corresponded to 74% (HCV-1a) and 35% (HCV-1b) of non-synonymous substitutions. We found nine PI-resistance-associated variants (V36A, T54S, V55I, Q80K, Q80R, V107I, I132V, D168E, M175L) in HCV-NS3 of 10 patients. There was no correspondence of resistance-associated variant profile between baseline and at 4 weeks. Moreover, these resistance variants at baseline and short-term treatment are not good predictors of outcome under triple therapy. Our study also shows a large number of others minor and major non-synonymous variants in HCV-NS3 early in telaprevir-based therapy that can be important for further drug resistance association studies with newly developed PI agents. Highlights • HCV-NS3 protease variants were analyzed at baseline and 4 weeks of triple therapy. • Synonymous and non-synonymous variants, even at low frequency, were detected. • Nine PI resistance mutations were identified in 10/16 patients in both time points. • There was no correspondence between resistance mutation at baseline and 4 weeks. • We provide a comprehensive databank of non-synonymous variants in HCV-NS3. |
| Databáze: | OpenAIRE |
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