1.0 Precis 
This phase I/ll pilot project will evaluate the survival, tolerance, safety, 
and efficacy of infusions of activated, gene marked, syngeneic T lymphocytes 
obtained from HIV seronegative identical twins on the functional immune 
status of HIV infected twin recipients. T cells from each seronegative twin will 
be obtained by periodic apheresis, separated into CD4 and CD8 enriched 
populations by monoclonal antibody affinity binding techniques, induced to 
polyclonal proliferation with anti-CD3 and rlL-2 stimulation, transduced with 
distinctive neoR retroviral vectors, and expanded 10-1,000 fold in numbers 
during approximately 2 weeks of culture. These marked T cell fractions will 
then be infused into the seropositive twins and the survival of the uniquely 
marked T cell populations will be monitored by vector-specific PCR, while the 
recipients' functional immune status is monitored by standard in vitro and in 
vivo testing protocols. A total of 3 cycles of treatment will be given at intervals 
of 6 weeks between infusions. 
2.0 Introduction 
2.1 Background 
An estimated one million Americans are infected with the human 
immunodeficiency virus, type 1 (HIV-1), a human retrovirus and causative 
agent of the acquired immunodeficiency syndrome (AIDS) (1-4). The Centers 
for Disease Control predicts there will be a total of 435,000 cases of AIDS by 
1993 and 312,000 deaths due to infection by HIV 1. Among hemophiliacs 
and users of illicit intravenous drugs, AIDS is now the leading cause of death 
(5). Worldwide it is estimated that between five and 10 million people are 
infected and that approximately one million new cases of AIDS will occur over 
the next five years (6). Considering current estimates of numbers of .infected 
individuals, projections of numbers of people who will become newly infected 
over the next several years, and the enormous amounts of resources often 
required in the care and management of people with HIV infection, it is clear 
that the current epidemic will make even greater demands on already-limited 
services. 
Therapeutic strategies for intervening in HIV disease currently include 
antiretroviral therapy, treatment and prophylaxis of opportunistic infections, 
anti-tumor therapy, immunomodulator therapy, and immunologic restoration. 
Zidovudine (AZT), an inhibitor of reverse transcriptase, was the first 
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