the risk that gene transfer poses to a patient cannot be accurately stated at 
present, but based on the accumulated experience the risk appears to be 
very low. 
Some of the potential hazards were illustrated in a primate model of 
retrovirally-mediated gene modification, where lethally irradiated rhesus 
monkeys were exposed to massive amounts of replication-competent 
retrovirus. When autologous stem cells used to reconstitute the bone marrow 
were incubated in vitro in the presence of retroviral vector particles with 
accompanying replication-competent virus, retroviral vector genome was 
detected in circulating cells of 5 of 8 of the transplant recipients of CD34+ cells 
and in 2 recipients of unfractionated bone marrow cells (37). Three 
recipients of CD34+ cells had a productive infection with replication 
competent virus. Within 7 months of transplantation, each of these three 
animals developed a rapidly progressive T cell neoplasm; lymphoma cells 
contained 10 to 50 copies of the replication competent virus but, importantly, 
lacked the retroviral vector. Thus, these tumors occurred in the setting of 
intentional contamination of the bone marrow transplant with replication 
competent virus, were associated with continuous retroviremia, but did not 
involve the retroviral vector. This experience underscores the importance of 
carefully screening retroviral producer clones used in human trials to exclude 
contamination with replication competent virus. 
In the more than 30 patients who have now received gene-modified cells, no 
evidence for the generation of replication-competent virus has been seen. 
Long term surveillance of exposed monkeys as well as the patients enrolled 
in the various clinical protocols will be necessary to better understand the 
actual frequency and severity of the risks associated with this procedure. The 
vectors that we are proposing to use in this protocol are produced by the 
same supplier as those used in other clinical protocols where there has been 
no evidence of helper virus contamination. 
4.0 Study Objectives 
4.1 To determine the distribution and longevity of adoptively 
transferred, genetically marked syngeneic peripheral blood CD4 
and CD8 lymphocytes in patients with HIV infection. 
4.2 To determine the safety and tolerance of the adoptive transfer of 
genetically marked syngeneic peripheral blooa lymphocytes in 
patients with HIV infection. 
4.3 To determine the efficacy of transfused polyclonal T cells in 
Recombinant DNA Research, Volume 16 
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