Safety, pharmacokinetics, and antiviral response of CD4-immunoglobulin G by intravenous bolus in AIDS and AIDS-related complex.

Abstract

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.

• Authors: A C Collier, R W Coombs, D Katzenstein, M Holodniy, J Gibson, J Mordenti, A E Izu, A M Duliege, A J Ammann, T Merigan
• Journal: Journal of acquired immune deficiency syndromes and human retrovirology : official publication of the International Retrovirology Association (J Acquir Immune Defic Syndr Hum Retrovirol) Vol. 10 Issue 2 Pg. 150-6 (Oct 01 1995) ISSN: 1077-9450 [Print] United States
• PMID: 7552478 (Publication Type: Clinical Trial, Clinical Trial, Phase I, Controlled Clinical Trial, Journal Article, Multicenter Study, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• CD4 Immunoadhesins
• HIV Core Protein p24
• Recombinant Proteins

Topics

• AIDS-Related Complex (immunology, metabolism, therapy)
• Acquired Immunodeficiency Syndrome (immunology, metabolism, therapy)
• Adult
• Blood Chemical Analysis
• CD4 Immunoadhesins (administration & dosage, adverse effects, therapeutic use)
• CD4 Lymphocyte Count
• Dose-Response Relationship, Drug
• Drug Tolerance
• HIV Core Protein p24 (analysis)
• HIV-1 (drug effects)
• Humans
• Injections, Intravenous
• Male
• Recombinant Proteins (administration & dosage, adverse effects, pharmacokinetics, therapeutic use)