Synergistic Interaction of 2',3'-Dideoxycytidine and Recombinant Interferon- -A on Replication of Human Immunodeficiency Virus Type 1

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Abstract
Effective treatment of infections with human immunodeficiency virus type 1(HIV-1) may require a combination of antiviral drugs that act by different mechanisms. We report that the combination of 2′,3′-dideoxycytidine (ddCyd) and recombinant interferon-α-A (rIFN-α-A) acts synergistically against HIV-1 replication in vitro. Variouscell types (peripheral blood leukocytes, a CD4-positive T cell line, and two monocyte-macrophage lines) have been studied. For each set of dose-effect data, the degree of drug interaction was quantitatively ssessed with the median-effect principle and the isobologram equation by using a computer analysis. Under various culture conditions using several concentrations of drugs, multiplicities of infectious virus, and assay systems, antiviral synergism was consistently observed against HIV-1 replication without enhanced celltoxicity. Synergism was seen at concentrations as low as 0.02 µM ddCyd plus 4 U of rIFN-α-A/mL or 0.01 µM ddCyd plus 8 U of rIFN-α-A/mL, whereas to-fold higher concentrations were usually required to achieve similar effects with single drugs.

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