Viral kinetics analysis and virological characterization of treatment failures in patients with chronic hepatitis C treated with sofosbuvir and an NS5A inhibitor
| Autor: | A. Varaut, M. Francois, J. Guedj, Lila Poiteau, Alexandre Soulier, Thi Huyen Tram Nguyen, Stéphane Chevaliez, Jean-Michel Pawlotsky, G. Scoazec, Christophe Hézode, A. Mallat, Isaac Ruiz, Slim Fourati, F. Roudot-Thoraval |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Male Pyrrolidines Sofosbuvir Sustained Virologic Response Hepacivirus Viral Nonstructural Proteins Gastroenterology Cohort Studies chemistry.chemical_compound 0302 clinical medicine Medicine Pharmacology (medical) Treatment Failure Aged 80 and over Standard treatment Imidazoles virus diseases Valine Middle Aged Viral Load Cohort 030211 gastroenterology & hepatology Drug Therapy Combination Female Uridine Monophosphate medicine.drug Ledipasvir Adult medicine.medical_specialty Daclatasvir Genotype Antiviral Agents 03 medical and health sciences Internal medicine Humans In patient NS5A Aged Fluorenes Hepatology business.industry Hepatitis C Chronic digestive system diseases Clinical trial Kinetics 030104 developmental biology chemistry Benzimidazoles Carbamates business |
| Zdroj: | Alimentary pharmacologytherapeutics. 47(5) |
| ISSN: | 1365-2036 |
| Popis: | BACKGROUND The combination of sofosbuvir (SOF) plus an NS5A inhibitor for 12 weeks is highly efficacious in patients with chronic hepatitis C. As the costs of generic production of sofosbuvir and NS5A inhibitor are rapidly decreasing, the combination of these DAAs will be the standard treatment in most low- to middle-income countries in the future. AIM To identify key predictors of response that can be used to tailor treatment decisions. METHODS A cohort of 216 consecutive patients infected with HCV genotype 1 (1a: n = 57; 1b: n = 77), 2 (n = 4), 3 (n = 33) or 4 (n = 44) were treated with sofosbuvir (SOF) + daclatasvir (n = 176) or SOF + ledipasvir (n = 40) for 12 weeks. The viral kinetics was analysed using the biphasic model and the cure boundary was used to predict time to clear HCV. RESULTS The overall SVR rate was high (94.4%; n = 204), regardless of the time to viral suppression or low-level viraemia at the end of treatment. The model-based predicted HCV RNA levels at the end of treatment could not differentiate patients who did from those who did not achieve SVR. The presence of NS5A resistance-associated substitutions [position 28 (OR = 70.3, P |
| Databáze: | OpenAIRE |
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