Project: Research project

    Project Details


    The clinical research component of this application describes an
    approach for sequential late Phase I and early Phase II studies in a
    group of 150 to 200 HIV seropositive hemophiliacs. These patients
    are a subpopulation of 400 multitransfused hemophiliacs who
    receive comprehensive care at three centers in the mid-Atlantic
    region and who are well characterized concerning their immune
    deficiency status. Efficacy of proposed initial therapy with AZT
    and Acyclovir will be evaluated in a concurrent case control study
    by measurement of T-cell subsets, serum IFN alpha levels, antigen
    capture assay, Western Blot analysis, and by neuropsychiatric
    assessment and clinical outcomes. Inhibition of viral replication
    will be assessed experimentally by tow unique model systems: (1)
    an in vitro flow cytometric detection system to identify as few as
    one HIV infected cell among 10,000 peripheral blood lymphocytes
    (currently under development by contract with the NHLBI), and
    (2) an in vivo human tissue xenograft system which we propose to
    develop and validate in a nude mouse host. To study the
    immunoreactivity of naturally occurring antibodies, an HIV DNA
    expression library will be constructed. If clinical status can be
    correlated with antibody response of infected individuals
    undergoing therapy, bacterially synthesized proteins will be used
    to produce monoclonal antibodies against specific HIV epitopes.
    These antibodies will then be tested for their ability to block HIV
    infections both in vitro and in vivo. The neutralizing and
    cytotoxic abilities of naturally occurring antibodies, and their
    specificities, will be studied using our two experimental model
    systems. Drug resistance will be assessed in vitro and in vivo in
    the nude mouse host. It is hoped that these clinical and basic
    research studies will contribute to a better understanding of the
    molecular genetics, immonobiology and natural history of HIV
    infections, and that they will lead to the development of better
    strategies for early intervention with antiviral drugs or vaccines.
    Effective start/end date1/1/901/1/90


    • National Institute of Allergy and Infectious Diseases

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