title: Successful pharmacogenetics-based optimization of unboosted atazanavir plasma exposure in HIV-positive patients: a randomized, controlled, pilot study (the REYAGEN study).
abstract: BACKGROUND
  Atazanavir without ritonavir, despite efficacy and tolerability, shows low plasma concentrations that warrant optimization.
  
  
  METHODS
  In a randomized, controlled, pilot trial, stable HIV-positive patients on atazanavir/ritonavir (with tenofovir/emtricitabine) were switched to atazanavir. In the standard-dose arm, atazanavir was administered as 400 mg once daily, while according to patients' genetics (PXR, ABCB1 and SLCO1B1), in the pharmacogenetic arm: patients with unfavourable genotypes received 200 mg of atazanavir twice daily. EudraCT number: 2009-014216-35.
  
  
  RESULTS
  Eighty patients were enrolled with balanced baseline characteristics. The average atazanavir exposure was 253 ng/mL (150-542) in the pharmacogenetic arm versus 111 ng/mL (64-190) in the standard-dose arm (P < 0.001); 28 patients in the pharmacogenetic arm (75.7%) had atazanavir exposure >150 ng/mL versus 14 patients (38.9%) in the standard-dose arm (P = 0.001). Immunovirological and laboratory parameters had a favourable outcome throughout the study with non-significant differences between study arms.
  
  
  CONCLUSIONS
  Atazanavir plasma exposure is higher when the schedule is chosen according to the patient's genetic profile.
authors.affiliation: Unit of Infectious Diseases, Department of Medical Sciences, University of Torino, Torino, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Bonora
authors.affiliation: Department of Infectious Diseases, Ospedale Luigi Sacco, University of Milano, Milano, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Rusconi
authors.affiliation: Unit of Infectious Diseases, Department of Medical Sciences, University of Torino, Torino, Italy andrea.calcagno@unito.it.
authors.forename: A
authors.initials: A
authors.lastname: Calcagno
authors.affiliation: Unit of Infectious Diseases, Department of Medical Sciences, University of Torino, Torino, Italy St Stephen's Centre, Chelsea and Westminster Hospital, London, UK.
authors.forename: M
authors.initials: M
authors.lastname: Bracchi
authors.affiliation: Department of Infectious Diseases, Ospedale Luigi Sacco, University of Milano, Milano, Italy.
authors.forename: O
authors.initials: O
authors.lastname: Viganò
authors.affiliation: Unit of Infectious Diseases, Department of Medical Sciences, University of Torino, Torino, Italy.
authors.forename: J
authors.initials: J
authors.lastname: Cusato
authors.affiliation: Unit of Diagnosis and Therapy of HIV Infection, 'G. B. Rossi' Hospital, 37134 Verona, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Lanzafame
authors.affiliation: Unit of Infectious Diseases, Department of Medical Sciences, University of Torino, Torino, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Trentalange
authors.affiliation: Unit of Infectious Diseases, Department of Medical Sciences, University of Torino, Torino, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Marinaro
authors.affiliation: Department of Pharmacology, University of Liverpool, Liverpool, UK.
authors.forename: M
authors.initials: M
authors.lastname: Siccardi
authors.affiliation: Unit of Infectious Diseases, Department of Medical Sciences, University of Torino, Torino, Italy.
authors.forename: A
authors.initials: A
authors.lastname: D'Avolio
authors.affiliation: Department of Infectious Diseases, Ospedale Luigi Sacco, University of Milano, Milano, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Galli
authors.affiliation: Unit of Infectious Diseases, Department of Medical Sciences, University of Torino, Torino, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Di Perri
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000235:genetics; D000328:Adult; D044966:Anti-Retroviral Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D000069446:Atazanavir Sulfate / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D005260:Female; D005819:Genetic Markers; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy*; D006801:Humans; D027381:Liver-Specific Organic Anion Transporter 1; D008297:Male; D008875:Middle Aged; D027361:Organic Anion Transporters / Q000235:genetics; D000074435:Peroxisome-Targeting Signal 1 Receptor; D010597:Pharmacogenetics / Q000379:methods*; D010865:Pilot Projects; D010949:Plasma / Q000737:chemistry*; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D044966:Anti-Retroviral Agents; D005819:Genetic Markers; D027381:Liver-Specific Organic Anion Transporter 1; D027361:Organic Anion Transporters; D000074435:Peroxisome-Targeting Signal 1 Receptor; D018160:Receptors, Cytoplasmic and Nuclear; C503999:SLCO1B1 protein, human; D000069446:Atazanavir Sulfate