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Session 113 Poster Abstracts
Pharmacology of Protease Inhibitors
Wednesday, 1:30 - 3:30 pm
Hall A


656    
The Clinical Correlations of Trough Plasma Atazanavir Levels in a Cohort of HIV-1-positive Individuals Receiving HAART
Alan Winston*1, M Bloch2, A Carr3, J Amin1, P Mallon1, J Ray3, D Marriott3, D Cooper1, and S Emery1
1Natl Ctr in HIV Epidemiology and Clin Res, Univ of New South Wales, Sydney, Australia; 2Holdsworth House Gen Practice, Sydney, Australia; and 3St Vincent's Hosp, Sydney, Australia

Background:  Atazanavir (ATV) is a recently approved HIV protease inhibitor (PI). As with other PI, careful attention to potential pharmacokinetic interactions in clinical practice is necessary. The aim of this study was to assess trough plasma ATV levels in a cohort of HIV-positive individuals receiving HAART containing ATV. In addition we wished to assess associations between dosing and prescribing practice and resultant levels.

Methods:  Individuals established on an ATV-containing antiretroviral regimen for > 28 days, were asked to attend to complete an interviewer administered questionnaire prior to usual dosing time. During the questionnaire ATV dosing characteristics, concomitant medication use, and adherence were assessed after which a trough plasma ATV level was performed. Factors associated with trough plasma ATV levels were assessed by linear regression analysis.

Results:  A total of 100 individuals completed the study protocol. Mean trough plasma ATV levels were 282 μg/L and 774 μg/L in those on non-boosted and ritonavir (RTV) boosted regimens respectively. Of the total, 85 individuals had HIV RNA below detectable levels (< 50 copies/mL); 7 had ATV plasma levels below the assay limit of detection (< 50 μg/L), all of whom had plasma HIV RNA below detectable limits. Of the 93 patients with ATV levels > 50 μg/L, 85 (91%) had undetectable plasma HIV RNA; 76 were on currently recommended dosing regimens and 24 were on other regimens. In a multivariate analysis, RTV use was significantly associated with a higher trough ATV level (p < 0.001) and nevirapine (NVP) was significantly associated with a lower trough ATV level (p = 0.011). The following factors were not significantly associated with trough plasma ATV levels:  dosing characteristics, including the use of recommended versus non-recommended dosing regimens, other medications (including antacids and other known contraindicated agents), and plasma HIV RNA.

Conclusions:  In this cohort of individuals on ATV-containing regimens, trough plasma ATV levels are significantly increased with the use of RTV, significantly decreased with the use of NVP and not significantly altered by ATV dosing characteristics or the concomitant use of regularly prescribed and non-prescribed medication.

Keywords: drug interaction; atazanavir; pharmacokinetics