Document 0189
 DOCN  M9550189
 TI    Combination therapy with recombinant human soluble CD4-immunoglobulin G
       and zidovudine in patients with HIV infection: a phase I study.
 DT    9505
 AU    Meng TC; Fischl MA; Cheeseman SH; Spector SA; Resnick L; Boota A;
       Petrakis T; Wright B; Richman DD; University of California, San Diego.
 SO    J Acquir Immune Defic Syndr Hum Retrovirol. 1995 Feb 1;8(2):152-60.
       Unique Identifier : AIDSLINE MED/95135993
 AB    To determine the effect of zidovudine (ZDV) on the pharmacokinetic
       disposition of recombinant soluble CD4 immunoglobulin G (rCD4-IgG) and
       to evaluate the safety and preliminary activity of concurrent
       administration of ZDV with rCD4-IgG, we undertook an open-label,
       dose-escalating, 12-week study. The regimens of intravenous rCD4-IgG and
       oral ZDV we used were (a) 300 micrograms/kg rCD4-IgG twice per week and
       300 mg ZDV per day, (b) 300 micrograms/kg rCD4-IgG twice per week and
       600 mg ZDV per day, (c) 1,000 micrograms/kg rCD4-IgG twice per week and
       300 mg ZDV per day, (d) 1,000 micrograms/kg rCD4-IgG twice per week and
       600 mg ZDV per day, and (e) 3,000 micrograms/kg rCD4-IgG twice per week
       and 300 mg ZDV per day. Subjects were recruited from three AIDS clinical
       trials units. Forty-one patients with HIV infection who had CD4 cell
       counts < or = 500 cells/mm3 and < 120 days of previous ZDV therapy
       participated. Pharmacokinetic interactions were assessed with the second
       regimen. Mean calculated peak serum rCD4-IgG concentrations were 5.47
       micrograms/ml with ZDV and 8.28 micrograms/ml without ZDV, with serum
       half-lives of 34.2 and 32.0 h, respectively. Antibodies to rCD4-IgG were
       not detected. Seven episodes of severe adverse events occurred in five
       patients: one episode each of severe nausea, fever, or abnormal liver
       function tests and four episodes of severe neutropenia. Mean hemoglobin
       and neutrophil counts decreased, and mean platelet counts increased in
       all regimens, but there were no significant differences among regimens,
       rCD4-IgG dose, or ZDV dose.(ABSTRACT TRUNCATED AT 250 WORDS)
 DE    Adult  CD4 Immunoadhesins/ADVERSE EFFECTS/*THERAPEUTIC USE  CD4
       Lymphocyte Count  Drug Interactions  Drug Therapy, Combination  Female
       Human  HIV Core Protein p24/BLOOD  HIV Infections/BLOOD/*DRUG
       THERAPY/IMMUNOLOGY  Male  Middle Age  Safety  United States  Viremia
       Zidovudine/ADVERSE EFFECTS/PHARMACOKINETICS/*THERAPEUTIC USE  CLINICAL
       TRIAL  CLINICAL TRIAL, PHASE I  JOURNAL ARTICLE

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