VIAGENE HIV-I-03-393 
PROTOCOL VERSION 1.4 
Title: An Open Label, Phase I/II Clinical Trial to Evaluate the Safety and 
Biological Activity of HIV-IT (V) (HIV- 1 IIIB c/zv/rcv-Retroviral Vector) 
in HIV-l-Infected Subjects 
1.0 Objectives 
1.1 Three monthly intramuscular injections of HIV-1 Immunotherapeutic vector 
[HIV-IT (V)] at a dose of approximately 10 million colony forming units (10 7 
cfu) will be administered to determine: 
1.1.1 Safety and tolerability of three monthly injections of HIV-IT (V). 
1.1.2 The effects on the specific cytotoxic T lymphocyte (CTL) response to HIV- 1 . 
1.1.3 Effects on HIV- 1 antibody levels. 
1.1.4 Effects on viral load. 
1.1.5 Effects on CD4+ and CD8 + T-cell subpopulations. 
1.1.6 Early clinical indications of effects on disease progress. 
2.0 Background and Rationale 
2.1 Immune Response to HIV-1 
2.1.1 Both cellular and humoral immune responses have been documented in HIV- 1 infected 
individuals. During acute HIV-1 infection, high titers of virus are present in the blood as 
established by cell culture and p24 detection. Recent studies have shown that CTL 
responses directed against GAG, POL, and ENV antigens occur earlier than neutralizing 
antibody (NA) responses and appear to mediate the decrease in viral load. 1 
2.1.2 The protective effect of anti-HIV- 1 NA is uncertain. Despite the presence of NA directed 
against the V3 loop and CD4 + combining site of gp 120, clearance of HIV-1 infection 
does not occur. HIV- 1 can evade NA by direct cell to cell spread. 2 The V3 loop shows 
considerable inter-strain variability and antibodies directed against this region are type 
specific but not group specific. Viral mutation in this region can lead to escape from the 
NA response. In addition, there has been no correlation between the level of NA and 
HIV-1 disease progression. 
2.1.3 To date, most immunotherapeutic vaccines have been targeted at the development of new 
or increased levels of antibody. There is now increasing evidence of the importance of 
CTL in preventing HIV-1 spread. The ability to increase CTL activity may be a potential 
method of controlling progression of HIV-1 infection. 3 
2. 1 .4 HIV-1 is a virus which can confound the immune system as follows: (1) Gene segments 
coding for the envelope protein mutate frequently, including those portions of the 
envelope which are immunodominant with respect to antibody production 4 , (2) HIV-1 
may down-regulate expression of major histocompatibility complex (MHC) molecules 
^afrit, et al., J. Cell Biochem. Suppl. 17E:Q146 (1993). 
2 Popovic, M., et al., Science, 224:497-500 (1984). 
3 Walker, B.D., et al., AIDS, 4:177-184 (1990). 
4 La Rosa, G. J., et al., Science, 249:932-935 (1990). 
Recombinant DNA Research, Volume 18 
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