IITRI proposes to use in vitro test-cell systems for evaluation of chemotherapies against HIV. The test systems will be used for measurement of antiviral activity of drugs in standardized cell-based HIV infectivity assays. For evaluation of the antiviral efficacy of drugs tested singly and/or in combination, the following assays are offered: (a) CPE-inhibition assay of HIV-1 using the human permanent CD4+ T cell lines, CEM and MT4, as targets for the virus. Cytotoxicity of tested drugs will be evaluated in these cell-systems as well; (b) inhibition of HIV-1 p24 core antigen production in virus infectivity assays using a human T cell line, H9, and a monocytic cell line, U-937, as targets for the virus infection; (c) in these p24 inhibition assays, fresh human peripheral blood (PB)-derived lymphocytes and monocyte/macrophages will be included as target-cells for the virus; cytotoxicity of the drugs will be evaluated in these normal cell-systems as well; (d) the antiviral efficacy of drugs will be evaluated in these neoplastic and normal cell-systems using different HIV-1, HIV-2 isolates as well as AZT-resistant and other drug resistant virus isolates. In addition, T cell lines chronically infected with HIV-1 (e.g.H9/HTLV- IIIb) will be included in these drugs studies; (e) singly or in combination antiviral therapeutic drugs will be evaluated for immunological modulating and toxic effects on immune systems cells of murine and human origin, and (f) a novel three-dimensional graphics program will be used for analyses of synergistic and antagonistic effects on antiviral activity and cytotoxicity of the drugs tested.
