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 ben 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 evaluation BRMs alone or in combination with other drugs in an retrovirusanimal model which mimics the disease AIDS.

Project Start
1987-09-01
Project End
1992-08-31
Budget Start
1987-09-01
Budget End
1988-08-31
Support Year
Fiscal Year
1987
Total Cost
Indirect Cost
Name
Colorado State University-Fort Collins
Department
Type
Schools of Veterinary Medicine
DUNS #
112617480
City
Fort Collins
State
CO
Country
United States
Zip Code
80523
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Kim, W K; Tang, Y; Kenny, J J et al. (1994) In murine AIDS, B cells are early targets of defective virus and are required for efficient infection and expression of defective virus in T cells and macrophages. J Virol 68:6767-9
Sidwell, R W; Hitchcock, M; Okleberry, K M et al. (1992) Suppression of murine retroviral disease by 2',3'-didehydro-2',3'-dideoxythymidine (D4T). Antiviral Res 19:313-24
Zeidner, N S; Myles, M H; Mathiason-DuBard, C K et al. (1990) Alpha interferon (2b) in combination with zidovudine for the treatment of presymptomatic feline leukemia virus-induced immunodeficiency syndrome. Antimicrob Agents Chemother 34:1749-56
Hoover, E A; Zeidner, N S; Mullins, J I (1990) Therapy of presymptomatic FeLV-induced immunodeficiency syndrome with AZT in combination with alpha interferon. Ann N Y Acad Sci 616:258-69
Hoover, E A; Zeidner, N S; Perigo, N A et al. (1989) Feline leukemia virus-induced immunodeficiency syndrome in cats as a model for evaluation of antiretroviral therapy. Intervirology 30 Suppl 1:12-25