title: Clinical evaluation of a dried blood spot assay for atazanavir.
abstract: Current procedures for obtaining and measuring plasma concentrations of HIV protease inhibitors (PIs) are technically challenging. Dried blood spot (DBS) assays offer a way to overcome many of the obstacles. We sought to develop a DBS assay for quantitation of the PI atazanavir (ATV) and to compare this method with a previously validated plasma assay. We prospectively enrolled 48 patients with well-controlled HIV disease who had been on ATV for at least 7 days. ATV was quantified from plasma by use of high-performance liquid chromatography (HPLC). A reversed-phase ultrahigh-performance liquid chromatography (UPLC) assay was utilized for DBS samples. The concentrations of ATV quantified in a DBS matrix showed very strong agreement with those measured in plasma (r(2) = 0.988). The mean difference in ATV concentration between the two methods was -10.8% (95% confidence interval [95% CI], -7.65% to -13.95%), indicating that the DBS method has a slight negative bias. A majority (97.8%) of the differences in concentration between the two assays fell within ±2 standard deviations. ATV concentrations were lower in subjects who had detectable HIV RNA in plasma (mean, 543 ng/ml) than in those with HIV RNA of <50 copies/ml (mean, 1,582 ng/ml) (P = 0.03, Wilcoxon rank-sum test). In conclusion, our study demonstrated that ATV quantitation in a DBS matrix is feasible and accurate. DBS use offers a convenient alternative for measuring plasma concentrations of ATV and may have utility in monitoring of drug concentrations in clinical practice and in future studies.
authors.affiliation: Department of Internal Medicine, Section of Infectious Diseases, University of Nebraska Medical Center, Nebraska Medical Center, Omaha, NE 68198-4031, USA. tvanscho@unmc.edu
authors.forename: Trevor
authors.initials: T
authors.lastname: Van Schooneveld
authors.forename: Susan
authors.initials: S
authors.lastname: Swindells
authors.forename: Sarah R
authors.initials: SR
authors.lastname: Nelson
authors.forename: Brian L
authors.initials: BL
authors.lastname: Robbins
authors.forename: Ryan
authors.initials: R
authors.lastname: Moore
authors.forename: Courtney V
authors.initials: CV
authors.lastname: Fletcher
mesh_terms: D000328:Adult; D000069446:Atazanavir Sulfate; D001681:Biological Assay; D002851:Chromatography, High Pressure Liquid; D005260:Female; D017320:HIV Protease Inhibitors / Q000097:blood*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009842:Oligopeptides / Q000097:blood*; D011725:Pyridines / Q000097:blood*; D015203:Reproducibility of Results; D055815:Young Adult
chemical_list: D017320:HIV Protease Inhibitors; D009842:Oligopeptides; D011725:Pyridines; D000069446:Atazanavir Sulfate