1. Viral kinetics analysis and virological characterization of treatment failures in patients with chronic hepatitis C treated with sofosbuvir and an NS5A inhibitor.
- Author
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Fourati S, Guedj J, Chevaliez S, Nguyen THT, Roudot-Thoraval F, Ruiz I, Soulier A, Scoazec G, Varaut A, Poiteau L, Francois M, Mallat A, Hézode C, and Pawlotsky JM
- Subjects
- Adult, Aged, Aged, 80 and over, Antiviral Agents adverse effects, Benzimidazoles therapeutic use, Carbamates, Cohort Studies, Drug Therapy, Combination adverse effects, Drug Therapy, Combination methods, Female, Fluorenes therapeutic use, Genotype, Hepacivirus genetics, Hepatitis C, Chronic virology, Humans, Imidazoles administration & dosage, Imidazoles adverse effects, Kinetics, Male, Middle Aged, Pyrrolidines, Sofosbuvir adverse effects, Sustained Virologic Response, Treatment Failure, Uridine Monophosphate analogs & derivatives, Uridine Monophosphate therapeutic use, Valine analogs & derivatives, Antiviral Agents administration & dosage, Hepatitis C, Chronic drug therapy, Sofosbuvir administration & dosage, Viral Load drug effects, Viral Nonstructural Proteins antagonists & inhibitors
- Abstract
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<.001) and/or 31 (OR = 61.6, P = .002)] at baseline was predictive of virological failure in cirrhotic patients but was not associated with on-treatment viral kinetics., Conclusion: This real-world study confirms the excellent results of clinical trials with therapies based on a combination of SOF plus an NS5A inhibitor. It suggests that a personalized approach including baseline NS5A inhibitor resistance testing may inform treatment decisions in cirrhotic patients., (© 2017 John Wiley & Sons Ltd.)
- Published
- 2018
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