Prevalence of hepatitis C virus variants resistant to NS3 protease inhibitors or the NS5A inhibitor (BMS-790052) in hepatitis patients with genotype 1b
| Autor: | Yuya Seko, Sachiyo Watahiki, Hitomi Sezaki, Satoshi Saito, Mariko Kobayashi, Fumitaka Suzuki, Hiromitsu Kumada, Norio Akuta, Rie Mineta, Yusuke Kawamura, Yasuji Arase, Masahiro Kobayashi, Yuzo Miyakawa, Tetsuya Hosaka, Kenji Ikeda, Yoshiyuki Suzuki |
|---|---|
| Rok vydání: | 2011 |
| Předmět: |
Adult
Male Pyrrolidines Adolescent Genotype Hepatitis C virus Molecular Sequence Data Drug resistance Hepacivirus Viral Nonstructural Proteins medicine.disease_cause Antiviral Agents chemistry.chemical_compound Young Adult Virology Drug Resistance Viral Prevalence Medicine Humans Protease Inhibitors NS5A Aged Hepatitis NS3 business.industry Ribavirin Imidazoles virus diseases Valine Sequence Analysis DNA Middle Aged medicine.disease Hepatitis C digestive system diseases Infectious Diseases chemistry Amino Acid Substitution Immunology Population study Female Carbamates business |
| Zdroj: | Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology. 54(4) |
| ISSN: | 1873-5967 |
| Popis: | Background Hepatitis C virus (HCV) of genotype 1b is the most prevalent worldwide, and the least responsive to interferon-based treatments. A combination therapy with two direct-acting antivirals has shown promising results in patients with HCV-1b, but the prevalence of drug-resistant variants before treatment is not known in the Japanese population. Objectives To detect HCV variants resistant to NS3 protease inhibitors or the NS5A inhibitor (BMS-790052) in hepatitis patients infected with HCV-1b. Study design Drug-resistant mutations were determined in the 362 hepatitis patients infected with HCV-1b who had not received direct-acting antivirals before. Results Amino-acid substitutions resistant to NS3 inhibitors (V36A, T54S, Q80H and D168E) were detected in 15 of the 307 (4.9%) patients, who had been examined, and T54S (3.3%) predominated over V36A (0.3%), Q80R (0.7%) and D168E (0.7%) in them. Amino-acid substitutions resistant to BMS-790052 (L31M and/or Y93H) were detected in 33 of the 294 (11.2%) patients, and Y93H (8.2%) predominated over L31M (2.7%). One of the 239 (0.4%) patients, who had been examined for amino-acid substitutions in both NS3 and NS5A regions, possessed HCV-1b variants resistant to NS3 inhibitors (T54S) and BMS-790052 (L31M). Conclusions Mutations conferring resistance to NS3 inhibitors or BMS-790052 were frequent in our treatment-naive study population, but double mutants with possible resistance to both drugs were rare. Since single mutations did not result in treatment failure in a previous pilot trial combining BMS-790052 and an NS3 inhibitor, larger trials of this drug regimen appear warranted in the Japanese population. |
| Databáze: | OpenAIRE |
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