title: Ribavirin Concentrations Do Not Predict Sustained Virological Response in HIV/HCV-Coinfected Patients Treated with Ribavirin and Pegylated Interferon in the Swiss HIV Cohort Study.
abstract: BACKGROUND
  Ribavirin (RBV) is an essential component of most current hepatitis C (HCV) treatment regimens and still standard of care in the combination with pegylated interferon (pegIFN) to treat chronic HCV in resource limited settings. Study results in HIV/HCV-coinfected patients are contradicting as to whether RBV concentration correlates with sustained virological response (SVR).
  
  
  METHODS
  We included 262 HCV treatment naïve HIV/HCV-coinfected Swiss HIV Cohort Study (SHCS) participants treated with RBV and pegIFN between 01.01.2001-01.01.2010, 134 with HCV genotype (GT) 1/4, and 128 with GT 2/3 infections. RBV levels were measured retrospectively in stored plasma samples obtained between HCV treatment week 4 and end of therapy. Uni- and multivariable logistic regression analyses were used to evaluate the association between RBV concentration and SVR in GT 1/4 and GT 2/3 infections. The analyses were repeated stratified by treatment phase (week 4-12, 13-24, >24) and IL28B genotype (CC versus CT/TT).
  
  
  RESULTS
  SVR rates were 35.1% in GT 1/4 and 70.3% in GT 2/3 infections. Overall, median RBV concentration was 2.0 mg/L in GT 1/4, and 1.9 mg/L in GT 2/3, and did not change significantly across treatment phases. Patients with SVR had similar RBV concentrations compared to patients without SVR in both HCV genotype groups. SVR was not associated with RBV levels ≥2.0 mg/L (GT 1/4, OR 1.19 [0.5-2.86]; GT 2/3, 1.94 [0.78-4.80]) and ≥2.5 mg/L (GT 1/4, 1.56 [0.64-3.84]; GT 2/3 2.72 [0.85-8.73]), regardless of treatment phase, and IL28B genotype.
  
  
  CONCLUSIONS
  In HIV/HCV-coinfected patients treated with pegIFN/RBV, therapeutic drug monitoring of RBV concentrations does not enhance the chance of HCV cure, regardless of HCV genotype, treatment phase and IL28B genotype.
authors.affiliation: Division of Infectious Diseases and Hospital Epidemiology, University Hospital, University of Zurich, Zurich, Switzerland.
authors.forename: Helen
authors.initials: H
authors.lastname: Kovari
authors.affiliation: Department of Clinical Pharmacology and Toxicology, University Hospital Zurich, Zurich, Switzerland.
authors.forename: Stefan
authors.initials: S
authors.lastname: Russmann
authors.affiliation: Division of Infectious Diseases and Hospital Epidemiology, University Hospital, University of Zurich, Zurich, Switzerland.
authors.forename: Bruno
authors.initials: B
authors.lastname: Ledergerber
authors.affiliation: Institute of Clinical Chemistry, University Hospital Zurich, Zurich, Switzerland.
authors.forename: Daniel
authors.initials: D
authors.lastname: Müller
authors.affiliation: Institute of Microbiology, University Hospital, Lausanne, Switzerland.
authors.forename: Margalida
authors.initials: M
authors.lastname: Rotger
authors.affiliation: Institute of Microbiology, University Hospital, Lausanne, Switzerland.
authors.forename: Pablo
authors.initials: P
authors.lastname: Velli
authors.affiliation: Division of Infectious Diseases, University Hospital, Lausanne, Switzerland.
authors.forename: Matthias
authors.initials: M
authors.lastname: Cavassini
authors.affiliation: Division of Infectious Diseases, University Hospital, Geneva, Switzerland.
authors.forename: Juan
authors.initials: J
authors.lastname: Ambrosioni
authors.affiliation: Division of Infectious Diseases, Cantonal Hospital, St. Gallen, Switzerland.
authors.forename: Andrea
authors.initials: A
authors.lastname: Bregenzer
authors.affiliation: Division of Infectious Diseases and Hospital Epidemiology, University Hospital, Basle, Switzerland.
authors.forename: Marcel
authors.initials: M
authors.lastname: Stöckle
authors.affiliation: Ospedale Regionale, Lugano, Switzerland.
authors.forename: Enos
authors.initials: E
authors.lastname: Bernasconi
authors.affiliation: University Clinic of Infectious Diseases, University Hospital Berne and University of Berne, Berne, Switzerland.
authors.forename: Andri
authors.initials: A
authors.lastname: Rauch
authors.affiliation: Division of Infectious Diseases and Hospital Epidemiology, University Hospital, University of Zurich, Zurich, Switzerland.
authors.forename: Roberto F
authors.initials: RF
authors.lastname: Speck
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use*; D060085:Coinfection / Q000097:blood* / Q000150:complications / Q000188:drug therapy / Q000821:virology; D016903:Drug Monitoring; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D015658:HIV Infections / Q000097:blood* / Q000150:complications / Q000188:drug therapy / Q000821:virology; D015497:HIV-1 / Q000187:drug effects; D016174:Hepacivirus / Q000187:drug effects; D019698:Hepatitis C, Chronic / Q000097:blood* / Q000150:complications / Q000188:drug therapy / Q000821:virology; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000627:therapeutic use*; D011446:Prospective Studies; D011994:Recombinant Proteins / Q000627:therapeutic use; D012254:Ribavirin / Q000097:blood* / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D000998:Antiviral Agents; D016898:Interferon-alpha; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; C100416:peginterferon alfa-2a