HIV infects 40 million people worldwide. In the United States (U.S.), it is estimated that almost one million people are infected with HIV. The mortality due to HIV/AIDS is estimated to be approximately three (3) million deaths annually worldwide, with 15,000 deaths per year in the U.S. The current standard of care for treatment of HIV is HAART, or highly active antiretroviral therapy. However, HAART is very expensive and requires a cumbersome dosing regimen. More importantly, an increasing number of resistant HIV strains are emerging as a result of drug therapy, and these resistant strains are being transmitted to newly infected individuals. This subpopulation of HIV drug-resistant patients has no treatment alternatives and therefore has a very poor prognosis. Our overall goal is to demonstrate the safety and efficacy of HIV-1-based vectors in delaying or preventing the onset of AIDS, the disease caused by HIV. Our technology uses HIV as a backbone to deliver an anti-HIV gene to infected CD4 T cells, which are the target cells for HIV replication. We have demonstrated in studies supported by Phase I SBIR funding that an HIV vector carrying an anti- HIV antisense genetic payload (VRX496) effectively inhibits productive HIV replication in patient CD4 T cells independent of patient viral load, CD4 count, and virus tropism. The key technological objectives of the proposed studies in this grant are to characterize the risk/benefit ratio of our therapy, and develop and validate the technology in-house for large-scale patient cell processing in preparation for U.S. efficacy clinical trials. To this end, our specific aims are: 1) determine whether lentiviral gene transfer induces clonal T cell lymphoproliferation in vivo, and catalog insertion sites in healthy and HIV-infected adult and pediatric donors, 2) evaluate the efficacy of our therapy in terms of immune reconstitution by measuring the immunological responses in VRX496-treated patients longitudinally, and 3) develop and validate the technology for in house large-scale cell processing for gene therapy treatment of HIV. These three key objectives are closely associated with the overall product safety and efficacy, which is an important step in moving forward to making our therapy available to those patients who would otherwise have no alternative treatment options.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Small Business Innovation Research Grants (SBIR) - Phase II (R44)
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Special Emphasis Panel (ZRG1-ADDT (10))
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Voulgaropoulou, Frosso
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Virxsys Corporation
United States
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Levine, Bruce L; Humeau, Laurent M; Boyer, Jean et al. (2006) Gene transfer in humans using a conditionally replicating lentiviral vector. Proc Natl Acad Sci U S A 103:17372-7