title: Relative impact of ribavirin monitoring and HIV coinfection on sustained virological response in patients with chronic hepatitis C.
abstract: BACKGROUND
  In chronic hepatitis C, higher ribavirin (RBV) concentrations are associated with sustained virological response (SVR); target concentration cutoffs have been proposed. As RBV displays interindividual variability, monitoring of RBV plasma levels appears relevant. The impact of RBV therapeutic drug monitoring (TDM(RBV)) on SVR has not been explored in current practice. Our study aimed to assess this impact.
  
  
  METHODS
  Three patient groups were defined as RBV cutoffs achieved at week 12 (group A1), not achieved (group A2), and one without RBV concentration assessment (group B). A predictive model assessed the group impact on SVR in multivariate analysis, while adjusting for additional predictive factors. A specific evaluation of HIV-HCV-coinfected patients was performed.
  
  
  RESULTS
  A total of 122 patients were included. In group A1 (n=30, HIV-positive =18), SVR, relapse and non-response rates were 60%, 17% and 23%, respectively; in group A2 (n=32, HIV-positive =18), 25%, 19% and 56%, respectively; and in group B (n=60, HIV-positive =3), 52%, 33% and 15%, respectively (P=0.0004). The patient group was an independent predictor of SVR (P=0.01), along with baseline viral load and HCV genotype. HIV coinfection did not impede the SVR rate. The cutoffs were achieved in 62% and 28% (P=0.008) of patients, when TDM(RBV) was performed or not, respectively.
  
  
  CONCLUSIONS
  The achievement of RBV cutoffs is a predictive factor of SVR independent of HIV coinfection. It makes it possible to reach high SVR rates, avoid relapse and obtain the same SVR rates in HIV-HCV-coinfected as in HCV-monoinfected patients. TDM(RBV) enables RBV concentration cutoffs to be reached more frequently and could thus be a useful tool to optimize hepatitis C treatment.
authors.affiliation: EA UPRES 3186, Laboratoire de Pharmacologie Clinique, CHU Besançon, Besançon, France. spiedoux@chu-besancon.fr
authors.forename: Sarah
authors.initials: S
authors.lastname: Piedoux
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Monnet
authors.forename: Lionel
authors.initials: L
authors.lastname: Piroth
authors.forename: Damien
authors.initials: D
authors.lastname: Montange
authors.forename: Bernard
authors.initials: B
authors.lastname: Royer
authors.forename: Thierry
authors.initials: T
authors.lastname: Thevenot
authors.forename: Jean Pierre
authors.initials: JP
authors.lastname: Kantelip
authors.forename: Vincent
authors.initials: V
authors.lastname: Di Martino
authors.forename: Patrice
authors.initials: P
authors.lastname: Muret
mesh_terms: D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000097:blood* / Q000493:pharmacokinetics; D015331:Cohort Studies; D060085:Coinfection; D016903:Drug Monitoring; D004359:Drug Therapy, Combination; D005260:Female; D005602:France; D006678:HIV / Q000187:drug effects / Q000502:physiology; D015658:HIV Infections / Q000097:blood* / Q000150:complications / Q000188:drug therapy / Q000821:virology; D016174:Hepacivirus / Q000187:drug effects* / Q000502:physiology; D019698:Hepatitis C, Chronic / Q000097:blood* / Q000150:complications / Q000188:drug therapy / Q000821:virology; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000627:therapeutic use; D011237:Predictive Value of Tests; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000627:therapeutic use; D012254:Ribavirin / Q000097:blood* / Q000493:pharmacokinetics; D016896:Treatment Outcome; D019562:Viral Load / Q000187:drug effects; D014779:Virus Replication / Q000187:drug effects*
chemical_list: D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; C417083:peginterferon alfa-2b; C100416:peginterferon alfa-2a