| Abstract: |
The combination of S-dC28 (a phosphorothioate oligodeoxcytidine 28 mer) with AZT, recombinant interferon α-A (IFN-αA) or dextran sulfate (DS) against replication of human immunodeficiency virus type 1 (HIV-1) were studied in MT4 cells, using both p24 core antigen and reverse transcriptase (RT) assays. Under the standardized conditions, the anti-HIV-1 dose-effect relationships of all test drugs showed sigmoidal curves with the following EC50 values: for the p24 core antigen assay, S-dC28, 0.03 μM; AZT, 0.004 μM; IFN-αA, 9.2 U/ml; DS, 0.26 μg/ml; for the RT assay, S-dC28, 0.04 μM; AZT, 0.01 μM; IFN-αA, 11.6 U/ml; and DS, 0.31 μg/ml. A computer software based on the median-effect principle and isobologram techniques were used to quantitatively analyze drug interactions by calculating the combination index (CI) where CI < 1, = 1, and > 1 indicates synergism, additive effect and antagonism, respectively. For p24-ELISA, the interaction of S-dC28 and AZT in combination produced a slight antagonism on HIV-1 replicative inhibition with CI values of 1.29-1.10; for RT assays, at EC50-EC95 levels, the CI values are 1.96-1.11. For p24 core antigen assay, the combination of S-dC28 with IFN-αA exhibited a dose-dependent anti-HIV synergism with CI values of 1.15-0.87 at EC75-EC95 levels. The RT assays for the same combination showed a broad synergistic effect with CI values of 0.62-0.60, at EC50-EC95 levels. S-dC28 plus DS showed a nearly additive effect based on both assay methods. The present studies document the lack of synergistic interaction in vitro between S-dC28 and AZT, or S-dC28 and DS. However, S-dC28 and IFN-αA yielded a synergistic effect in which the dose-reduction indices indicate that lower doses of each drug can be used in combination to achieve increased efficacy without detectable cytotoxicity. © 1991, Mary Ann Liebert, Inc. All rights reserved. |
| Keywords: |
unclassified drug; drug efficacy; drug potentiation; nonhuman; alpha interferon; comparative study; human immunodeficiency virus infection; t-lymphocytes; cell line; tumor cells, cultured; drug synergism; drug therapy, combination; deoxycytidine; antiviral activity; human immunodeficiency virus 1; hiv-1; zidovudine; leukemia, t-cell; dextran sulfate; thionucleotides; interferon type i, recombinant; human; article; oligodeoxynucleotide phosphorothioate; support, non-u.s. gov't; support, u.s. gov't, p.h.s.; s dc28
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