Galpin/DA/N2 niBenv 
of toxicity. Studies evaluating the localization and persistence of the vector in mice have also 
been conducted. 
No animal models accurately parallel the clinical or immunological course of human HIV 
infection and disease. Only human clinical trials can address the efficacy of this new 
treatment modality. 
The initial focus is to establish the human safety of its retroviral vector-mediated gene- 
transfer treatment. Asymptomatic HIV-1 infected patients will be treated with the genetically 
engineered, non-replicating, amphotropic murine retroviral vector encoding the HIV-1 IIIB 
envelope protein (N2 IIIBenv). Three monthly intramuscular injections of the retroviral 
vector will be administered. Five subjects will receive initial doses of 10 6 cfu and be 
compared to placebo injections for tolerability and immunogenic activity. Ten additional 
subjects (five new subjects and the placebo group) will each receive doses at 10 7 cfu. If no 
significant toxicity is observed in the low dose group, subjects treated will be assessed for 
acute and chronic toxicity, viral load, antibody and CTL response, and any evidence of 
clinical efficacy. 
Development of highly sensitive assays for the detection of replication-competent 
retrovirus (RCR) has been part of the exhaustive attention focused on the development of 
packaging cell lines free of this problem. 
The N2 IIIBenv retroviral vector exemplifies a new research direction for treatment of 
HIV/AIDS. We believe that this clinical protocol for asymptomatic, HIV-1 positive patients 
has a very favorable risk-benefit ratio. Amplifying both specific antibody and cell-mediated 
immune response in the HIV infected human host is biologically justifiable, clinically 
reasonable, and socially desirable. The success of this form of treatment also offers a 
cost-effective modality which could be administered without economic bias worldwide. 
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