       Document 0625
 DOCN  M9610625
 TI    Safety, pharmacokinetics, and antiviral response of CD4-immunoglobulin G
       by intravenous bolus in AIDS and AIDS-related complex.
 DT    9601
 AU    Collier AC; Coombs RW; Katzenstein D; Holodniy M; Gibson J; Mordenti J;
       Izu AE; Duliege AM; Ammann AJ; Merigan T; et al; Department of Medicine,
       University of Washington, Seattle, USA.
 SO    J Acquir Immune Defic Syndr Hum Retrovirol. 1995 Oct 1;10(2):150-6.
       Unique Identifier : AIDSLINE MED/96007276
 AB    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.
 DE    Acquired Immunodeficiency Syndrome/IMMUNOLOGY/METABOLISM/*THERAPY  Adult
       AIDS-Related Complex/IMMUNOLOGY/METABOLISM/*THERAPY  Blood Chemical
       Analysis  CD4 Immunoadhesins/ADMINISTRATION & DOSAGE/ADVERSE EFFECTS/
       *THERAPEUTIC USE  CD4 Lymphocyte Count  Dose-Response Relationship, Drug
       Drug Tolerance  Human  HIV Core Protein p24/ANALYSIS  HIV-1/*DRUG
       EFFECTS  Injections, Intravenous  Male  Recombinant
       Proteins/ADMINISTRATION & DOSAGE/ADVERSE EFFECTS/
       PHARMACOKINETICS/THERAPEUTIC USE  Support, U.S. Gov't, P.H.S.  CLINICAL
       TRIAL  CLINICAL TRIAL, PHASE I  CONTROLLED CLINICAL TRIAL  JOURNAL
       ARTICLE  MULTICENTER STUDY

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).

