JAC Advance Access published online on August 17, 2007
Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dkm298
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Therapeutic drug monitoring of the HIV protease inhibitor atazanavir in clinical practice
1 Department of Clinical Pharmacy, Radboud University Medical Centre Nijmegen, The Netherlands 2 Nijmegen University Centre for Infectious Diseases (NUCI), Radboud University Medical Center Nijmegen, The Netherlands 3 Department of Internal Medicine, Erasmus Medical Centre Rotterdam, The Netherlands 4 Department of Infectious Diseases, Leiden University Medical Centre, The Netherlands 5 Department of Medical Microbiology, Radboud University Medical Centre Nijmegen, The Netherlands 6 Department of General Internal Medicine, Radboud University Medical Centre, The Netherlands 7 HIV Monitoring Foundation, Amsterdam, The Netherlands
Received 6 May 2007; returned 6 July 2007; revised 9 July 2007; accepted 13 July 2007
* Correspondence address. Department of Clinical Pharmacy, 864 Radboud UMC Nijmegen, Geert Grooteplein 10, 6525 GA Nijmegen, The Netherlands. Tel: +31-24-3616405; Fax: +31-24-3668755; E-mail: d.burger{at}akf.umcn.nl
Background: Therapeutic drug monitoring (TDM) is being applied for a number of antiretroviral agents. Little is known about the use of TDM for atazanavir.
Methods: This is a retrospective cohort analysis on the use of TDM of atazanavir at three clinical sites in The Netherlands. Patients were divided into three groups: (i) all patients with evaluable data of plasma atazanavir concentrations and its relationship with hyperbilirubinaemia; (ii) patients who started atazanavir without documented evidence of protease inhibitor (PI) mutations; (iii) patients who started atazanavir with documented evidence of PI mutations. The genotypic inhibitory quotient (GIQ) was calculated by dividing the mean atazanavir plasma trough concentration by the number of PI mutations.
Results: A total of 108 patients were included; 70 (65.8%) were using atazanavir/ritonavir (300/100 mg once daily). No significant relationship was observed between atazanavir plasma trough concentration and antiviral response in patients starting atazanavir without PI mutations (group 2; n = 82). In contrast, a significant relationship was observed between atazanavir GIQ and treatment response in patients starting atazanavir while having PI mutations (group 3; n = 26). The cut-off value for GIQ most predictive of virological failure was 0.23 mg/L/mutation: patients (n = 8) with a GIQ equal to or below this value had 50% virological failure whereas patients (n = 18) with a GIQ above 0.23 mg/L/mutation had only 11% virological failure (
2: P = 0.030). Atazanavir plasma trough concentrations were significantly related with the occurrence of increased total bilirubin concentrations.
Conclusions: TDM of atazanavir might be beneficial for patients with documented PI resistance or patients with hyperbilirubinaemia.
Key Words: pharmacokinetics , resistance , hyperbilirubinaemia
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