title: Lower Ribavirin Plasma Concentrations in HCV/HIV-Coinfected Patients Than in HCV-Monoinfected Patients Despite Similar Dosage.
abstract: BACKGROUND
  Hepatitis C virus (HCV)/HIV-coinfected patients respond worse to dual therapy with ribavirin (RBV)/peginterferon compared with HCV-monoinfected patients. Several trials found that lower RBV plasma concentrations are associated with impaired virological response rates. The aim of this study was to determine RBV plasma concentrations in a cohort of HCV-monoinfected and HCV/HIV-coinfected patients. Our hypothesis is that HCV/HIV-coinfected patients have lower RBV plasma concentrations, which may in part explain their inferior response to dual therapy.
  
  
  METHODS
  A retrospective cohort study was performed in chronic HCV-monoinfected and HCV/HIV-coinfected patients who received peginterferon and weight-based RBV. Plasma RBV concentrations were determined at weeks 4 and 12 by a validated high-performance liquid chromatography assay. RBV concentrations were compared between monoinfected and coinfected patients. We calculated the proportion of patients with a subtherapeutic RBV plasma concentration defined as <2.0 mg/L.
  
  
  RESULTS
  A total of 61 HCV-infected patients were included, of whom 21 (34%) were coinfected with HIV. Although there was no difference in the weight-based dose of RBV between monoinfected and coinfected patients, RBV exposure was significantly lower in HCV/HIV-coinfected patients than in HCV-monoinfected patients: the mean ± SD RBV plasma concentrations were 1.82 ± 0.63 mg/L versus 2.25 ± 0.80 mg/L (P = 0.04) at week 4 and 2.14 ± 0.65 mg/L versus 2.62 ± 0.81 mg/L (P = 0.05) at week 12, respectively. The percentage of patients with subtherapeutic plasma concentrations of RBV in coinfected patients versus monoinfected patients was 62% versus 46% (P = 0.240) at week 4 and 50% versus 16% (P = 0.01) at week 12 of treatment, respectively.
  
  
  CONCLUSIONS
  HIV/HCV-coinfected patients yield significantly lower plasma concentrations of RBV than HCV-monoinfected patients. This puts them at an increased risk of not achieving sustained virological response.
authors.affiliation: *Department of Pharmacy, Radboud University Medical Center, Nijmegen; †Department of Clinical Pharmacy, Rijnstate Hospital, Arnhem; ‡Nijmegen Institute for Health Sciences, Radboud University Medical Center, Nijmegen; §Department of General Internal Medicine, Radboud University Medical Center, Nijmegen; ¶Department of Internal Medicine, Canisius Wilhelmina Hospital, Nijmegen; ‖Department of Clinical Pharmacy, Canisius Wilhelmina Hospital, Nijmegen; **Department of Internal Medicine, Rijnstate Hospital, Arnhem; and ††Department of Internal Medicine, Division of Gastroenterology and Hepatology, Radboud University Medical Center, Nijmegen, the Netherlands.
authors.forename: Maarten J
authors.initials: MJ
authors.lastname: Deenen
authors.forename: Clara T M M
authors.initials: CT
authors.lastname: de Kanter
authors.forename: Anthonius S M
authors.initials: AS
authors.lastname: Dofferhoff
authors.forename: Karin J T
authors.initials: KJ
authors.lastname: Grintjes-Huisman
authors.forename: Andre J A M
authors.initials: AJ
authors.lastname: van der Ven
authors.forename: Hanneke W H A
authors.initials: HW
authors.lastname: Fleuren
authors.forename: Elizabeth H
authors.initials: EH
authors.lastname: Gisolf
authors.forename: Peter P
authors.initials: PP
authors.lastname: Koopmans
authors.forename: Joost P H
authors.initials: JP
authors.lastname: Drenth
authors.forename: David M
authors.initials: DM
authors.lastname: Burger
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D015331:Cohort Studies; D060085:Coinfection; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000150:complications*; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D007372:Interferons / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000737:chemistry; D012189:Retrospective Studies; D012254:Ribavirin / Q000008:administration & dosage / Q000493:pharmacokinetics*; D013997:Time Factors
chemical_list: D000998:Antiviral Agents; D011092:Polyethylene Glycols; D012254:Ribavirin; D007372:Interferons