title: Erythrocyte and plasma ribavirin concentrations in the assessment of early and sustained virological responses to pegylated interferon-alpha 2a and ribavirin in patients coinfected with hepatitis C virus and HIV.
abstract: OBJECTIVE
  To determine the relationship between erythrocyte and plasma ribavirin concentrations in hepatitis C virus (HCV)/HIV-coinfected patients, and to correlate ribavirin exposure with early and sustained virological response (EVR and SVR) and haemoglobin level reductions.
  
  
  METHODS
  Clinical and biological data from 68 HCV/HIV-coinfected patients were recorded at baseline, week 4 (W4), week 12 and at 24 weeks after completion of treatment. Plasma and erythrocyte ribavirin concentrations were determined 12 h after the final ribavirin dose (C(min)).
  
  
  RESULTS
  Erythrocyte ribavirin concentrations were 100-fold higher than plasma concentrations, with a significant relationship between them (P < 0.05). In patients with HCV genotype 1 or 4, a plasma ribavirin C(min) threshold of 1.95 mg/L at W4 tended to predict EVR [sensitivity 44%; specificity 87%; AUC 0.67 (95% CI 0.50-0.84)] and was predictive of SVR [sensitivity 58%; specificity 84%; AUC 0.71 (95% CI 0.51-0.90)]. Among patients with these HCV genotypes, an erythrocyte ribavirin C(min) threshold of 146 mg/L at W4 was found to be the best value for discriminating between responders and non-responders for both EVR [sensitivity 67%; specificity 75%; AUC 0.58 (95% CI 0.24-0.93)] and SVR [sensitivity 50%; specificity 80%; AUC 0.70 (95% CI 0.39-1.01)]. We also demonstrated a significant relationship between reduced haemoglobin levels and plasma ribavirin C(min) at W4 (P = 0.05).
  
  
  CONCLUSIONS
  Therapeutic drug monitoring may be useful for the management of anti-HCV treatment in HCV/HIV-coinfected patients.
authors.affiliation: Service Immunologie Clinique, Hôpital Henri Mondor, Créteil, France. stephanie.dominiguez@hmn.aphp.fr
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Dominguez
authors.forename: Jade
authors.initials: J
authors.lastname: Ghosn
authors.forename: Bruno
authors.initials: B
authors.lastname: Cassard
authors.forename: Giovanna
authors.initials: G
authors.lastname: Melica
authors.forename: Isabelle
authors.initials: I
authors.lastname: Poizot-Martin
authors.forename: Caroline
authors.initials: C
authors.lastname: Solas
authors.forename: Anne-Sophie
authors.initials: AS
authors.lastname: Lascaux
authors.forename: Magali
authors.initials: M
authors.lastname: Bouvier-Alias
authors.forename: Christine
authors.initials: C
authors.lastname: Katlama
authors.forename: Yves
authors.initials: Y
authors.lastname: Lévy
authors.forename: Gilles
authors.initials: G
authors.lastname: Peytavin
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000008:administration & dosage / Q000032:analysis*; D004912:Erythrocytes / Q000737:chemistry*; D015658:HIV Infections / Q000150:complications*; D006454:Hemoglobins / Q000032:analysis; D006526:Hepatitis C / Q000150:complications* / Q000188:drug therapy*; D006801:Humans; D016898:Interferon-alpha / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D010949:Plasma / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000008:administration & dosage; D011994:Recombinant Proteins / Q000008:administration & dosage; D012254:Ribavirin / Q000008:administration & dosage / Q000032:analysis*; D016896:Treatment Outcome; D019562:Viral Load
chemical_list: D000998:Antiviral Agents; D006454:Hemoglobins; D016898:Interferon-alpha; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; C100416:peginterferon alfa-2a