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Safety, Pharmacokinetics, and Antiviral Response of CD4-Immunoglobulin G by Intravenous Bolus in AIDS and AIDS-Related Complex

Collier Ann C.; Coombs, Robert W.; Katzenstein, David; Holodniy, Mark; Gibson, Joel; Mordenti, Joyce; Izu, Allen E.; Duliege, Anne Marie; Ammann, Arthur J.; Merigan, Thomas; Corey, Lawrence
JAIDS Journal of Acquired Immune Deficiency Syndromes: October 1st, 1995

Summary: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 μg/kg weekly; 1,000 μg/kg once, twice, or three times per week; or 3,000 μg/kg twice weekly. Serum concentrations of CD4-IgG increased linearly with dose, with average peak serum concentrations of 22 μg/ml with 1,000 μg/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.

Address correspondence and reprint requests to Dr. Ann C. Collier at 1001 Broadway, Suite 218, Seattle, WA 98122, U.S.A.

Manuscript received July 13, 1994; accepted January 13, 1995.

© Lippincott-Raven Publishers.