Atazanavir trough plasma concentration monitoring in a cohort of HIV-1-positive individuals receiving highly active antiretroviral therapy

Objectives: Atazanavir is a recently approved Hill protease inhibitor (PI). As with other Pis, careful attention to potential pharmacokinetic drug interactions in clinical practice is necessary. The aim of this study was to assess the clinical associations with plasma atazanavir concentrations in HIV-positive individuals. Methods: Individuals established on an atazanavir-containing regimen, completed an interviewer-administered questionnaire recording atazanavir dosing characteristics, concomitant medication use and adherence. After completion, plasma atazanavir concentrations were measured. Results: Of 100 individuals, mean trough plasma atazanavir concentrations (mu g/L) were 282 (95% CI 95-468, n = 19) and 774 (95% CI 646-902, n = 81) in those on non- and ritonavir-boosted atazanavir regimens, respectively. Eighty-five individuals had HIV RNA < 50 copies/mL. Seven individuals had atazanavir plasma concentrations below the assay limit of detection (< 50 mu g/L), all of whom had undetectable plasma HIV RNA. In a multivariate analysis, nevirapine use was associated with significantly lower trough atazanavir concentrations (P = 0.011) and lopinavir/ritonavir use with higher trough atazanavir concentrations (P = 0.032). Dosing characteristics (including food taken), concomitant medications (including drugs used for dyspepsia) and HIV RNA were not significantly associated with trough atazanavir concentrations. Conclusions: In this cohort, despite the wide inter-individual variability of atazanavir trough concentrations, no significant association with dosing characteristics, concomitant medication (with the exception of nevirapine and lopinavir/ritonavir) or virological response was observed. Further work is needed to assess the optimal dosing regimen when using atazanavir with nevirapine.