Evolutionary dynamics of hepatitis C virus NS3 protease domain during and following treatment with narlaprevir, a potent NS3 protease inhibitor
| Autor: | X.V. Thomas, M. A. Treitel, R.J. de Knegt, Richard Molenkamp, Christine J. Weegink, Janke Schinkel, H. W. Reesink, J. de Bruijne, E. Hughes, J.F. Bergmann, H.L.A. Janssen, Sjoerd Rebers |
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| Přispěvatelé: | Amsterdam Gastroenterology Endocrinology Metabolism, Gastroenterology and Hepatology, Medical Microbiology and Infection Prevention, Experimental Immunology, Amsterdam institute for Infection and Immunity, Hematology, Gastroenterology & Hepatology |
| Jazyk: | angličtina |
| Rok vydání: | 2013 |
| Předmět: |
Adult
Cyclopropanes Male Proline Hepatitis C virus Population Hepacivirus Interferon alpha-2 Viral Nonstructural Proteins Biology medicine.disease_cause Antiviral Agents Polyethylene Glycols Evolution Molecular chemistry.chemical_compound SDG 3 - Good Health and Well-being Leucine Virology Ribavirin medicine Humans Urea Protease Inhibitors Protease inhibitor (pharmacology) Longitudinal Studies Sulfones education education.field_of_study NS3 Hepatology Interferon-alpha Dipeptides Sequence Analysis DNA Hepatitis C Chronic Middle Aged Viral Load Recombinant Proteins Infectious Diseases chemistry Narlaprevir Drug Therapy Combination Female Ritonavir Viral load medicine.drug |
| Zdroj: | Journal of viral hepatitis, 20(11), 779-789. Wiley-Blackwell Journal of Viral Hepatitis, 20(11), 779-789. Wiley-Blackwell Publishing Ltd |
| ISSN: | 1352-0504 |
| Popis: | Narlaprevir, a hepatitis C virus (HCV) NS3/4A serine protease inhibitor, has demonstrated robust antiviral activity in a placebo-controlled phase 1 study. To study evolutionary dynamics of resistant variants, the NS3 protease sequence was clonally analysed in thirty-two HCV genotype 1-infected patients following treatment with narlaprevir. Narlaprevir monotherapy was administered for one week (period 1) followed by narlaprevir/pegylated interferon-alpha-2b combination therapy with or without ritonavir (period 2) during two weeks, interrupted by a washout period of one month. Thereafter, all patients initiated pegylated interferon-alpha-2b/ribavirin combination therapy. Longitudinal clonal analysis was performed in those patients with NS3 mutations. After narlaprevir re-exposure, resistance-associated mutations at position V36, T54, R155 and A156 were detected in five patients in >95% of the clones. Narlaprevir retreatment resulted in a 2.58 and 5.06 log(10)IU/mL viral load decline in patients with and without mutations, respectively (P= |
| Databáze: | OpenAIRE |
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