S Bonora1, S Rusconi2, A Calcagno3, M Bracchi4, O Viganò2, J Cusato1, M Lanzafame5, A Trentalange1, L Marinaro1, M Siccardi6, A D'Avolio1, M Galli2, G Di Perri1. 1. Unit of Infectious Diseases, Department of Medical Sciences, University of Torino, Torino, Italy. 2. Department of Infectious Diseases, Ospedale Luigi Sacco, University of Milano, Milano, Italy. 3. Unit of Infectious Diseases, Department of Medical Sciences, University of Torino, Torino, Italy andrea.calcagno@unito.it. 4. Unit of Infectious Diseases, Department of Medical Sciences, University of Torino, Torino, Italy St Stephen's Centre, Chelsea and Westminster Hospital, London, UK. 5. Unit of Diagnosis and Therapy of HIV Infection, 'G. B. Rossi' Hospital, 37134 Verona, Italy. 6. Department of Pharmacology, University of Liverpool, Liverpool, UK.
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 onatazanavir/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.
RCT Entities:
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.
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