uu.seUppsala University Publications
Change search
ReferencesLink to record
Permanent link

Direct link
External Validation of the Bilirubin-Atazanavir Nomogram for Assessment of Atazanavir Plasma Exposure in HIV-1-Infected Patients
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences. (Pharmacometrics group)
Show others and affiliations
2013 (English)In: AAPS Journal, ISSN 1550-7416, Vol. 15, no 2, 308-315 p.Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
2013. Vol. 15, no 2, 308-315 p.
National Category
Medical and Health Sciences
URN: urn:nbn:se:uu:diva-190307DOI: 10.1208/s12248-012-9440-8ISI: 000317136100002PubMedID: 23224752OAI: oai:DiVA.org:uu-190307DiVA: diva2:583279
Available from: 2013-01-07 Created: 2013-01-07 Last updated: 2013-05-27Bibliographically approved

Open Access in DiVA

No full text

Other links

Publisher's full textPubMed

Search in DiVA

By author/editor
Bergstrand, Martin
By organisation
Department of Pharmaceutical Biosciences
In the same journal
AAPS Journal
Medical and Health Sciences

Search outside of DiVA

GoogleGoogle Scholar
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

Altmetric score

Total: 172 hits
ReferencesLink to record
Permanent link

Direct link