The effect of increasing alpha(1)-acid glycoprotein concentration on the antiviral efficacy of human immunodeficiency virus protease inhibitors

Citation
Xq. Zhang et al., The effect of increasing alpha(1)-acid glycoprotein concentration on the antiviral efficacy of human immunodeficiency virus protease inhibitors, J INFEC DIS, 180(6), 1999, pp. 1833-1837
Citations number
19
Categorie Soggetti
Clinical Immunolgy & Infectious Disease",Immunology
Journal title
JOURNAL OF INFECTIOUS DISEASES
ISSN journal
00221899 → ACNP
Volume
180
Issue
6
Year of publication
1999
Pages
1833 - 1837
Database
ISI
SICI code
0022-1899(199912)180:6<1833:TEOIAG>2.0.ZU;2-9
Abstract
The effect of a 4-fold increase in alpha(1)-acid glycoprotein (AGP) on the antiviral efficacy of 5 human immunodeficiency virus (HIV) protease inhibit ors (PIs) was examined by the effect of HIV PIs on p24 production in periph eral blood mononuclear cells infected with protease wild-type and PI-resist ant HIV isolates. For wild-type virus, the efficacy of the PIs at trough co ncentrations was unaffected by a 4-fold increase in AGP. With the partially HIV PI-resistant isolate, a 4-fold increase in AGP resulted in 2%, 30%, 37 %, 37%, and 42% loss of activity for indinavir, saquinavir, nelfinavir, rit onavir, and amprenavir, respectively. The high-level HIV PI-resistant isola te had a greater loss in activity. The change in IC50 secondary to the addi tion of AGP was the greatest for ritonavir, nelfinavir, and amprenavir and lowest for indinavir, These data suggest that the target plasma concentrati on for the highly bound HIV PIs may need to be raised in subjects with elev ated AGP who harbor partially PI-resistant isolates.