Successful pharmacogenetics-based optimization of unboosted atazanavir plasma exposure in HIV-positive patients: a randomized, controlled, pilot study (the REYAGEN study)

Atazanavir without ritonavir, despite efficacy and tolerability, shows low plasma concentrations that warrant optimization. In a randomized, controlled, pilot trial, stable HIV-positive patients on atazanavir/ritonavir (with tenofovir/emtricitabine) were switched to atazanavir. In the standard-dose...

Full description

Saved in:
Bibliographic Details
Published in:Journal of antimicrobial chemotherapy 2015-11, Vol.70 (11), p.3096-3099
Main Authors: Bonora, S, Rusconi, S, Calcagno, A, Bracchi, M, Viganò, O, Cusato, J, Lanzafame, M, Trentalange, A, Marinaro, L, Siccardi, M, D'Avolio, A, Galli, M, Di Perri, G
Format: Article
Language:English
Subjects:
Adult
Anti-Retroviral Agents - administration & dosage
Anti-Retroviral Agents - pharmacokinetics
Antiretroviral drugs
Atazanavir Sulfate - administration & dosage
Atazanavir Sulfate - pharmacokinetics
ATP Binding Cassette Transporter, Sub-Family B - genetics
Clinical trials
Female
Genetic Markers
Genetics
Genotype
Genotype & phenotype
HIV
HIV Infections - drug therapy
Human immunodeficiency virus
Humans
Male
Middle Aged
Organic Anion Transporters - genetics
Peroxisome-Targeting Signal 1 Receptor
Pharmacogenetics - methods
Pharmacology
Pilot Projects
Plasma - chemistry
Receptors, Cytoplasmic and Nuclear - genetics
Solute Carrier Organic Anion Transporter Family Member 1b1
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Atazanavir without ritonavir, despite efficacy and tolerability, shows low plasma concentrations that warrant optimization. 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. 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 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. Atazanavir plasma exposure is higher when the schedule is chosen according to the patient's genetic profile.
ISSN:0305-7453
1460-2091
DOI:10.1093/jac/dkv208