Safety, pharmacokinetics, and antiviral response of CD4-immunoglobulin G by intravenous bolus in AIDS and AIDS-related complex.
To assess the safety, pharmacokinetics, and antiviral effects of intravenous recombinant CD4 immunoglobulin G (CD4-IgG), a 12-week Phase One study with an optional maintenance phase was performed. Twenty-two subjects with advanced human immunodeficiency virus (HIV) infection were enrolled; 15 subjects completed the initial 12 weeks. CD4-IgG doses were 30, 100, or 300 micrograms/kg weekly; 1,000 micrograms/kg once, twice, or three times per week; or 3,000 micrograms/kg twice weekly. Serum concentrations of CD4-IgG increased linearly with dose, with average peak serum concentrations of 22 micrograms/ml with 1,000 micrograms/kg. CD4-IgG was well tolerated; one patient had self-limited tachycardia and flushing associated with CD4-IgG therapy. No changes were seen in CD4 cell counts, hematologic or coagulation studies, serum chemistries, HIV p24 antigen titers, or plasma HIV titers. No subject developed anti-CD4 antibodies. HIV isolates from five patients had IC90 values that were higher than the peak concentrations of CD4-IgG achieved in those patients. Additional studies that achieve higher CD4-IgG concentrations are necessary to evaluate the antiviral activity of this compound.
Collier
A C
AC
Department of Medicine, University of Washington, Seattle, USA.
Coombs
R W
RW
Katzenstein
D
D
Holodniy
M
M
Gibson
J
J
Mordenti
J
J
Izu
A E
AE
Duliege
A M
AM
Ammann
A J
AJ
Merigan
T
T
D000386:AIDS-Related Complex / Q000276:immunology / Q000378:metabolism / Q000628:therapy*; D000163:Acquired Immunodeficiency Syndrome / Q000276:immunology / Q000378:metabolism / Q000628:therapy*; D000328:Adult; D001774:Blood Chemical Analysis; D016860:CD4 Immunoadhesins / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D018791:CD4 Lymphocyte Count; D004305:Dose-Response Relationship, Drug; D004361:Drug Tolerance; D016655:HIV Core Protein p24 / Q000032:analysis; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use
D016860:CD4 Immunoadhesins; D016655:HIV Core Protein p24; D011994:Recombinant Proteins