Since the acquired immunodeficiency syndrome (AIDS) has been refractory to traditional pharmacologic interventions, alternative approaches have been developed. For example, gene products can be introduced in vivo to confer protection against HIV infection by stimulation of the immune system or by preventing infection of otherwise susceptible cells. We have described methods to stimulate immune responses in vivo, and a human gene therapy protocol is being performed to assess the safety and toxicity of gene transfer for AIDS by developing approaches to inhibit HIV replication in CD4+ cells. We have evaluated the efficacy of a transdominant mutant protein, Rev M10, against lymphocytes (PBL's) and have described several methods of gene transfer into PBLs from HIV-infected individuals. Gold microparticles, as well as retroviral vectors, can mediate stable Rev M10 gene transfer into these cells and inhibit productive viral replication of cloned and clinical HIV isolates without altering normal T cell function. Delivery of HIV protective genes will facilitate the development of gene therapy for AIDS and the analysis of viral and cellular gene expression in human T lymphocytes. This trial and other novel antiviral strategies will be described.

Acquired Immunodeficiency Syndrome/*THERAPY CD4-Positive T-Lymphocytes/VIROLOGY Gene Products, rev/GENETICS *Gene Therapy HIV-1/ISOLATION & PURIF/PHYSIOLOGY Human Virus Replication/GENETICS ABSTRACT

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