Immune based therapeutic trials for HIV-1 infection can be designed to ask the following questions: 1. Can we target host elements required for HIV propagation without unacceptable toxicities? Targeting host elements required for each phase of the viral life cycle may limit viral propagation without promoting escape mutation. Since HIV infects immunocompetent cells, immunologic toxicities are a predictable consequence of this approach. On the other hand, the redundancy of host immune responses may limit the impact of these toxicities. 2. What is the role of immune activation in HIV-1 disease pathogenesis? Immune dysregulation manifested as lymphocyte activation and heightened expression of pro-inflammatory cytokines may underlie auto-immune and certain other manifestations of HIV infection such as thrombocytopenia, HIV-associated renal failure and aphthous ulcers. Preliminary data suggest that renal immunosuppressive therapies targeting these processes may provide clinical benefit. 3. Can we enhance host defenses against HIV 1? If host defenses are important in regulation of viral expression, therapies designed to boast HIV-1 specific defenses may provide clinical benefit. Ex vivo expansion of HIV-1 specific cytotoxic T Lymphocytes and passive administration of polyclonal of monoclonal HIV-1 specific antibodies are in clinical trial. 4. Can we reconstitute immune responses in HIV disease? Immune responses may be reconstituted after administration of newer more active antiretrovirals. On the other hand the degree to which the immune dysfunction in AIDS is reversible is unknown. The immunorestorative activity of immune activating cytokines and the feasibility of immune restoration with ex-vivo expanded lymphoid populations of progenitor cells rendered resistant to HIV-1 by introduction of viral resistance constructs is under study. Immune based therapeutic trials may provide novel means of therapy for HIV-1 infection and also can compliment basic research by testing hyotheses of AIDS pathogenesis.

HIV Infections/COMPLICATIONS/IMMUNOLOGY/*THERAPY Human Immunization, Passive *Immunotherapy Lymphocyte Transformation ABSTRACT

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