The effect of increasing alpha1-acid glycoprotein concentration on the antiviral efficacy of human immunodeficiency virus protease inhibitors.
The effect of a 4-fold increase in alpha1-acid glycoprotein (AGP) on the antiviral efficacy of 5 human immunodeficiency virus (HIV) protease inhibitors (PIs) was examined by the effect of HIV PIs on p24 production in peripheral blood mononuclear cells infected with protease wild-type and PI-resistant HIV isolates. For wild-type virus, the efficacy of the PIs at trough concentrations 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, ritonavir, and amprenavir, respectively. The high-level HIV PI-resistant isolate had a greater loss in activity. The change in IC50 secondary to the addition of AGP was the greatest for ritonavir, nelfinavir, and amprenavir and lowest for indinavir. These data suggest that the target plasma concentration for the highly bound HIV PIs may need to be raised in subjects with elevated AGP who harbor partially PI-resistant isolates.
Zhang
X Q
XQ
Department of Medicine, Division of Infectious Diseases, University of Colorado Health Sciences Center, Denver, Colorado, USA.
Schooley
R T
RT
Gerber
J G
JG
D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D016655:HIV Core Protein p24 / Q000378:metabolism; D015658:HIV Infections / Q000821:virology; D017320:HIV Protease Inhibitors / Q000494:pharmacology*; D015497:HIV-1 / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D020128:Inhibitory Concentration 50; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000821:virology; D009961:Orosomucoid / Q000494:pharmacology*; D014779:Virus Replication / Q000187:drug effects
D016655:HIV Core Protein p24; D017320:HIV Protease Inhibitors; D009961:Orosomucoid