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.
Successful pharmacogenetics-based optimization of unboosted atazanavir plasma exposure in HIV-positive patients : a randomized, controlled, pilot study (the REYAGEN study) / S. Bonora, S. Rusconi, A. Calcagno, M. Bracchi, O. Viganò, J. Cusato, M. Lanzafame, A. Trentalange, L. Marinaro, M. Siccardi, A. D'Avolio, M. Galli, G. Di Perri. - In: JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY. - ISSN 0305-7453. - 70:11(2015), pp. 3096-3099.
|Titolo:||Successful pharmacogenetics-based optimization of unboosted atazanavir plasma exposure in HIV-positive patients : a randomized, controlled, pilot study (the REYAGEN study)|
RUSCONI, STEFANO (Secondo)
GALLI, MASSIMO (Penultimo)
|Parole Chiave:||Pharmacology; Pharmacology (medical); Infectious Diseases|
|Settore Scientifico Disciplinare:||Settore MED/17 - Malattie Infettive|
|Data di pubblicazione:||2015|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1093/jac/dkv208|
|Appare nelle tipologie:||01 - Articolo su periodico|