Publication: External validation of the bilirubin-atazanavir nomogram for assessment of atazanavir plasma exposure in HIV-1-infected patients
Issued Date
2013-04-01
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ISSN
15507416
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2-s2.0-84877044540
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Mahidol University
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SCOPUS
Bibliographic Citation
AAPS Journal. Vol.15, No.2 (2013), 308-315
Suggested Citation
Dinko Rekić, Daniel Röshammar, Martin Bergstrand, Joel Tarning, Andrea Calcagno, Antonio D'Avolio, Vidar Ormaasen, Marie Vigan, Aurélie Barrail-Tran, Michael Ashton, Magnus Gisslén, Angela Äbelö External validation of the bilirubin-atazanavir nomogram for assessment of atazanavir plasma exposure in HIV-1-infected patients. AAPS Journal. Vol.15, No.2 (2013), 308-315. doi:10.1208/s12248-012-9440-8 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/32744
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Title
External validation of the bilirubin-atazanavir nomogram for assessment of atazanavir plasma exposure in HIV-1-infected patients
Other Contributor(s)
Goteborg University, Sahlgrenska Academy
AstraZeneca Sweden
Uppsala Universitet
Mahidol University
Nuffield Department of Clinical Medicine
Universita degli Studi di Torino
Oslo University Hospital
Universite Paris 7- Denis Diderot
Inserm
Hopital de Bicetre
Universite Paris-Sud XI
Sahlgrenska Universitetssjukhuset
AstraZeneca Sweden
Uppsala Universitet
Mahidol University
Nuffield Department of Clinical Medicine
Universita degli Studi di Torino
Oslo University Hospital
Universite Paris 7- Denis Diderot
Inserm
Hopital de Bicetre
Universite Paris-Sud XI
Sahlgrenska Universitetssjukhuset
Abstract
Atazanavir increases plasma bilirubin levels in a concentration-dependent manner. Due to less costly and readily available assays, bilirubin has been proposed as a marker of atazanavir exposure. In this work, a previously developed nomogram for detection of suboptimal atazanavir exposure is validated against external patient populations. The bilirubin nomogram was validated against 311 matching bilirubin and atazanavir samples from 166 HIV-1-infected Norwegian, French, and Italian patients on a ritonavir-boosted regimen. In addition, the nomogram was evaluated in 56 Italian patients on an unboosted regimen. The predictive properties of the nomogram were validated against observed atazanavir plasma concentrations. The use of the nomogram to detect non-adherence was also investigated by simulation. The bilirubin nomogram predicted suboptimal exposure in the patient populations on a ritonavir-boosted regimen with a negative predictive value of 97% (95% CI 95-100). The bilirubin nomogram and monitoring of atazanavir concentrations had similar predictive properties for detecting non-adherence based on simulations. Although both methods performed adequately during a period of non-adherence, they had lower predictive power to detect past non-adherence episodes. Using the bilirubin nomogram for detection of suboptimal atazanavir exposure in patients on a ritonavir-boosted regimen is a rapid and cost-effective alternative to routine measurements of the actual atazanavir exposure in plasma. Its application may be useful in clinical settings if atazanavir concentrations are not available. © 2012 The Author(s).