CD4 cells is profound immunosuppression, leaving the patient 
unprotected against opportunistic infections and cancers, which cause 
the morbidity and mortality of HTV infection. 
4.2. 1 .4 Given these tactics by the virus, it is not altogether surprising that the 
therapeutic contributions made by humoral and cellular immunity in the 
control of the pathologic effects of HTV- 1 infection are poorly 
understood. HIV-1 specific antibodies, some of which possess in vitro 
neutralizing activity?, are generated during the natural course of HTV- 1 
infection. Neutralizing antibodies may eliminate extracellular virus m 
vivo , but HTV-1 can also spread by cell-to-cell fusion. Thus HIV 
infection and spread may continue in the presence of antibody. 
Epidemiologic studies and preliminary, investigations using passive 
immunotherapy further confirm that clinical disease and infectivity can 
be only partially delayed by even high levels of neutralizing antibody. 
4.2. 1 . 5 T-cell mediated immunity, involving the induction of CD8 + CTL that 
directly destroy virus-infected cells, has been shown to be important in 
limiting the severity and duration of several viral diseases^. CD8 + 
CTL, capable of lysing target cells expressing HTV-1 envelope, gag, 
polymerase, and nef proteins have been detected in HTV-1 seropositive 
patients, and may be important in controlling HIV-1 infection^. 
Although the precise impact of the immune response on HTV-1 infection 
remains to be elucidated, it is likely that the viral infection and 
replication process does not permit the full therapeutic benefit of the 
immune response to be invoked. 
4.2.2 Rationale for an HIV-1 Gene Transfer Immunotherapeutic 
4.2.2. 1 Given these considerations, the rationale for use of HIV-IT (V) is: (1) 
To attempt to stimulate the immune system, particularly CD8 + CTL 
induction, more broadly and to a more vigorous level than is allowed by 
the natural virus infection, and (2) To provide this immune stimulation 
as early as possible post-HIV- 1 infection, thereby mobilizing the 
^Robert-Guroff, M., et al, Nature, 316:72-74 (1985) 
^ Rouse, R.T., Rev. Infect. Dis., 10:16-33 (1988). 
^Koenig, S., et al, J. Immunol. 145:127-135 (1990). 
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