The objective of this contract is to facilitate the entry of biological response modifiers (BRMs) into clinical trials. This will be accomplished by examining the potential efficacy of BRMs in an appropriate retrovirus infected animal model. Efforts will be made to evaluate BRMs alone or in combination with other drugs in an appropriate animal/retrovirus model to determine their potential usefulness as a therapy for AIDS. BRMs are agents or methods used to alter the host's biological response to infection with a resultant therapeutic effect. BRMs may function in several ways. Some increase the host's antiviral responses by augmenting or restoring the effector arms directly or indirectly. Others may function to increase the growth and differentiation of lymphocytes or macrophages thus increasing the ability of the host to tolerate damage by cytotoxic drugs that may be used in the treatment of AIDS. Cytokines, lymphokines, monokines, growth factors, tumor necrosis factors and inducers of these proteins are examples of some of the BRMs known to date. The Division of Cancer Treatment (DCT) of the National Cancer Institute has been developing these agents in the treatment of tumors. Until recently little work has been done to develop the use of BRMs alone or in combination with other drugs for the treatment of viral infections. It may be that therapies for AIDS which require long term treatment with an antiviral agent (e.g. nucleoside analogue) may require combination therapy with a modulator of the immune response. BRMs could be used to decrease the toxicity of the drug by increasing the number of lymphocytes or aid in the immune response against this viral infection. At present, research into this area needs to be increased. It is the purpose of this solicitation to develop the use of BRMs for AIDS therapy. This will be accomplished by evaluating BRMs alone or in combination with other drugs in an retrovirusanimal model which mimics the disease AIDS.
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