title: Lower ribavirin biodisponibility in patients with HIV-HCV coinfection in comparison with HCV monoinfected patients.
abstract: BACKGROUND
  In HIV infected patients, the impact of ribavirin (RBV) pharmacology on sustained virologic response (SVR) to hepatitis C virus (HCV) treatment has not been fully investigated. The objective of this study was to compare the early RBV plasma exposure between a population of HIV-HCV coinfected patients and an HCV monoinfected group.
  
  
  METHODS
  Early RBV plasma exposure (expressed as Area Under the Curve (AUC) from 0 to 4 h) after a 600 mg first dose of RBV was measured in a population of HIV-HCV coinfected patients in comparison with an HCV monoinfected group. Peripheral blood samples were collected before the 600 mg RBV first dose (T0) to ensure no detectable baseline plasma RBV, and then 30 mn, 1, 2 and 4 hours after RBV intake (T0.5, T1, T2 and T4).
  
  
  RESULTS
  Eighty-six patients with chronic hepatitis C entered the study among whom 23 (27%) were HIV-HCV coinfected. Coinfected patients had a significantly lower RBV-AUC(0-4h) (median: 1469 μg*h/L [range 936-3677]) compared with monoinfected patients (2030 μg*h/L [851-7700]; p = 0.018). This RBV under exposure in coinfected patients persisted after normalization of AUC to RBV dose per kilogram of body weight (182 μg*h/L [110-425] versus 271 μg*h/L [82-1091], p = 0.001).
  
  
  CONCLUSIONS
  These results suggest that lower early bioavailability of RBV could be one of the reasons for lower SVR in HIV-HCV coinfected patients treated with pegylated interferon/RBV combination therapy. RBV plasma underexposure seems to be associated with the immunological status of the patients with lower AUC(0-4h) values observed in the more immunosuppressed coinfected patients.
authors.forename: Giorgiana
authors.initials: G
authors.lastname: Hatu
authors.forename: François
authors.initials: F
authors.lastname: Bailly
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Pourcelot
authors.affiliation: Department of Hepatology, Hôpital de la Croix-Rousse, Hospices Civils de Lyon, 103 grande rue de la Croix-Rousse, 69004 Lyon, France. pierre.pradat@univ-lyon1.fr.
authors.forename: Pierre
authors.initials: P
authors.lastname: Pradat
authors.forename: Patrick
authors.initials: P
authors.lastname: Miailhes
authors.forename: Marianne
authors.initials: M
authors.lastname: Maynard
authors.forename: François
authors.initials: F
authors.lastname: Parant
authors.forename: Pierre
authors.initials: P
authors.lastname: Chiarello
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Livrozet
authors.forename: Fabien
authors.initials: F
authors.lastname: Zoulim
authors.forename: Marie-Claude
authors.initials: MC
authors.lastname: Gagnieu
mesh_terms: D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D001682:Biological Availability; D060085:Coinfection; D005260:Female; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism* / Q000821:virology; D019698:Hepatitis C, Chronic / Q000097:blood / Q000188:drug therapy / Q000378:metabolism* / Q000821:virology; D006801:Humans; D008297:Male; D008875:Middle Aged; D012254:Ribavirin / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D055815:Young Adult
chemical_list: D000998:Antiviral Agents; D012254:Ribavirin