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Published on: March 30, 2014
Successful pharmacogenetics-based optimization of unboosted atazanavir plasma exposure in HIV-positive patients: a
S Bonora1, S Rusconi2, A Calcagno3
1Unit of Infectious Diseases, Department of Medical Sciences, University of Torino, Torino, Italy.
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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