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
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.