title: Sofosbuvir plus daclatasvir with or without ribavirin for chronic hepatitis C infection: Impact of drug concentration on viral load decay.
abstract: BACKGROUND
  Sofosbuvir (SOF) plus daclatasvir (DCV) with or without ribavirin is one of the currently recommended treatment option for chronic hepatitis C.
  
  
  OBJECTIVE
  Our objectives were to identify factors associated with SOF/DCV plasma concentrations [C] variations and to evaluate their impact on viral kinetics.
  
  
  METHODS
  130 consecutive HCV patients initiating SOF/DCV therapy with or without ribavirin were enrolled. Clinical, biological, virological and pharmacological data were collected at baseline, at week 4, 8, 12, and 24 of therapy and 12 weeks after the end of therapy.
  
  
  RESULTS
  Mean age was 57 years, 68% of patients were males, 69% were infected by HCV genotype 1 and cirrhosis was observed in 76% of patients. Multivariate analysis showed that higher SOF [C] and DCV [C] during treatment were associated with eGFR impairment and absence of cirrhosis. We found a significant correlation between the magnitude of HCV viral load decrease from day 0 to week 4 and a higher SOF [C] at week 4 (p=0.032) and a higher DCV [C] at week 8 (p=0.013).
  
  
  CONCLUSIONS
  Pharmacological monitoring showed significant associations between elevated SOF or DCV [C] and absence of cirrhosis, decreased eGFR and viral load decrease during the first month of treatment.
authors: Department of Hepatology, Groupement Hospitalier Nord, Hospices Civils de Lyon, Lyon, France; Lyon University, Lyon, France; Cancer Research Center of Lyon, UMR Inserm U1052, CNRS 5286, Lyon, France.
authors: Victor
authors: V
authors: Virlogeux
authors: Department of Hepatology, Groupement Hospitalier Nord, Hospices Civils de Lyon, Lyon, France.
authors: Laure
authors: L
authors: Choupeaux
authors: Department of Hepatology, Groupement Hospitalier Nord, Hospices Civils de Lyon, Lyon, France; Lyon University, Lyon, France; Cancer Research Center of Lyon, UMR Inserm U1052, CNRS 5286, Lyon, France.
authors: Pierre
authors: P
authors: Pradat
authors: Department of Hepatology, Groupement Hospitalier Nord, Hospices Civils de Lyon, Lyon, France; Lyon University, Lyon, France; Cancer Research Center of Lyon, UMR Inserm U1052, CNRS 5286, Lyon, France.
authors: Marianne
authors: M
authors: Maynard
authors: Department of Hepatology, Groupement Hospitalier Nord, Hospices Civils de Lyon, Lyon, France; Lyon University, Lyon, France; Cancer Research Center of Lyon, UMR Inserm U1052, CNRS 5286, Lyon, France.
authors: François
authors: F
authors: Bailly
authors: Department of Virology, Groupement Hospitalier Nord, Hospices Civils de Lyon, Lyon, France.
authors: Caroline
authors: C
authors: Scholtès
authors: Department of Pharmacology, Hôpital Edouard Herriot, Hospices Civils de Lyon, Lyon, France.
authors: Marie-Claude
authors: MC
authors: Gagnieu
authors: Department of Hepatology, Groupement Hospitalier Nord, Hospices Civils de Lyon, Lyon, France; Lyon University, Lyon, France; Cancer Research Center of Lyon, UMR Inserm U1052, CNRS 5286, Lyon, France. Electronic address: fabien.zoulim@inserm.fr.
authors: Fabien
authors: F
authors: Zoulim
mesh_terms: D000368:Aged; D000998:Antiviral Agents / Q000097:blood* / Q000627:therapeutic use; D002219:Carbamates; D016903:Drug Monitoring; D004359:Drug Therapy, Combination; D005260:Female; D005602:France; D005919:Glomerular Filtration Rate; D016174:Hepacivirus; D019698:Hepatitis C, Chronic / Q000150:complications / Q000188:drug therapy*; D006801:Humans; D007093:Imidazoles / Q000097:blood* / Q000627:therapeutic use; D016014:Linear Models; D008103:Liver Cirrhosis / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011759:Pyrrolidines; D012189:Retrospective Studies; D012254:Ribavirin / Q000627:therapeutic use; D000069474:Sofosbuvir / Q000097:blood* / Q000627:therapeutic use; D016896:Treatment Outcome; D014633:Valine / Q000031:analogs & derivatives; D019562:Viral Load
chemical_list: D000998:Antiviral Agents; D002219:Carbamates; D007093:Imidazoles; D011759:Pyrrolidines; D012254:Ribavirin; D014633:Valine; C549273:daclatasvir; D000069474:Sofosbuvir
keywords: Cirrhosis; Direct acting antiviral agents; HCV; Pharmacological monitoring