Hepatitis C Virus Genotype 4 Resistance and Subtype Demographic Characterization of Patients Treated with Ombitasvir plus Paritaprevir/Ritonavir
| Autor: | Coleen Hall, Liangjun Lu, Tami Pilot-Matias, Thomas Reisch, Christine Collins, Rakesh Tripathi, Tatyana Dekhtyar, Regis A. Vilchez, Preethi Krishnan, Gretja Schnell, Jill Beyer |
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| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
Adult
Cyclopropanes Male Macrocyclic Compounds Genotype Proline Hepacivirus Hepatitis C virus viruses Lactams Macrocyclic medicine.disease_cause Antiviral Agents chemistry.chemical_compound Young Adult Drug Resistance Viral medicine Humans Pharmacology (medical) Anilides NS5A Phylogeny Pharmacology Sulfonamides Ritonavir biology Ribavirin virus diseases Valine Hepatitis C biochemical phenomena metabolism and nutrition Hepatitis C Chronic Middle Aged medicine.disease biology.organism_classification Virology Ombitasvir digestive system diseases Infectious Diseases Treatment Outcome chemistry Paritaprevir Drug Therapy Combination Female Carbamates medicine.drug |
| Zdroj: | Antimicrobial Agents and Chemotherapy |
| ISSN: | 1098-6596 0066-4804 |
| Popis: | Hepatitis C virus (HCV) genotype 4 (GT4) is genetically diverse, with 17 confirmed subtypes, and comprises approximately 13% of infections worldwide. In this study, we identified GT4 subtypes by phylogenetic analysis, assessed differences in patient demographics across GT4 subtypes, examined baseline sequence variability among subtypes and the potential impact on treatment outcome, and analyzed the development of viral resistance in patients who received a regimen of ombitasvir (nonstructural protein 5A [NS5A] inhibitor) plus ritonavir-boosted paritaprevir (NS3/4A inhibitor) with or without ribavirin (RBV) for the treatment of HCV GT4 infection. Phylogenetic analysis of HCV NS3/4A, NS5A, and NS5B nucleotide sequences identified 7 subtypes (4a, 4b, 4c, 4d, 4f, 4g/4k, and 4o) among 132 patient samples. Subtype prevalence varied by country, and the distributions of patient birth cohort and race were significantly different across GT4 subtypes 4a, 4d, and non-4a/4d. Baseline amino acid variability was detected in NS5A across GT4 subtypes but had no impact on treatment outcome. Three patients experienced virologic failure and were infected with subtype 4d, and the predominant resistance-associated variants at the time of failure were D168V in NS3 and L28V in NS5A. Overall, high response rates were observed among patients infected with 7 HCV GT4 subtypes, with no impact of baseline variants on treatment outcome. GT4 subtype distribution in this study differed based on patient demographics and geography. |
| Databáze: | OpenAIRE |
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