Atazanavir trough plasma concentration monitoring in a cohort of HIV-1-positive individuals receiving highly active antiretroviral therapy.
OBJECTIVE
Atazanavir is a recently approved HIV 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 (mug/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 microg/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.
Winston
Alan
A
National Centre in HIV Epidemiology and Clinical Research, University of New South Wales, Sydney, 2010, Australia. alan_winston71@yahoo.co.uk
Bloch
Mark
M
Carr
Andrew
A
Amin
Janaki
J
Mallon
Patrick W G
PW
Ray
John
J
Marriott
Debbie
D
Cooper
David A
DA
Emery
Sean
S
D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000097:blood* / Q000627:therapeutic use; D023241:Antiretroviral Therapy, Highly Active; D000069446:Atazanavir Sulfate; D015331:Cohort Studies; D004334:Drug Administration Schedule; D005260:Female; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy* / Q000821:virology; D015497:HIV-1 / Q000187:drug effects* / Q000302:isolation & purification; D006801:Humans; D008297:Male; D009842:Oligopeptides / Q000008:administration & dosage / Q000097:blood* / Q000627:therapeutic use; D011725:Pyridines / Q000008:administration & dosage / Q000097:blood* / Q000627:therapeutic use; D012367:RNA, Viral / Q000032:analysis
D019380:Anti-HIV Agents; D009842:Oligopeptides; D011725:Pyridines; D012367:RNA, Viral; D000069446:Atazanavir Sulfate