Publication Abstract Display
Type: Published Manuscript
Title: Therapeutic amprenavir concentrations in cerebrospinal fluid.
Authors: Croteau D, Letendre S, Best BM, Rossi SS, Ellis RJ, Clifford DB, Collier AC, Gelman BB, Marra CM, McArthur J, McCutchan JA, Morgello S, Simpson DM, Way L, Capparelli E, Grant I; and the CHARTER Group
Year: 2012
Publication: Antimicrobial Agents and Chemotherapy
Volume: 56 Issue: 4 Pages: 1985-89
Abstract:Antiretrovirals that reach higher concentrations in cerebrospinal fluid (CSF) are associated with better control of HIV in CSF and possibly better neurocognitive performance. The objective of this study was to determine whether amprenavir (APV) concentrations in CSF are in the therapeutic range. Individuals were selected based on use of fosamprenavir (FPV)-containing regimens, a prodrug of APV, and the availability of stored CSF and matched plasma. Total APV was measured in 119 matched CSF-plasma pairs from 75 subjects by high performance liquid chromatography (HPLC) (plasma) or liquid chromatography tandem mass spectrometry (LC/MS/MS) (CSF). Concentrations were compared to the 50% inhibitory concentration (IC(50)) for wild-type HIV (5.6 ng/mL). Subjects were predominantly middle-aged (median 44 years) white (57%) men (78%) with AIDS (77%). APV was detected in all but 4 CSF specimens with a median concentration of 24.8 ng/mL (IQR 16.2-44.0). The median CSF-to-plasma ratio was 0.012 (IQR 0.008, 0.018). CSF concentrations correlated with plasma concentrations (rho = 0.61, p < 0.0001) and with post-dose sampling interval. APV concentrations in CSF exceeded the median IC(50) of wild-type HIV in more than 97% of CSF specimens with detectable APV by a median of 4.4-fold (IQR 2.9-7.9). We conclude that regimens containing fosamprenavir should contribute to control of HIV replication in the CNS as components of effective antiretroviral regimens.

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