Synergistic interaction of 2',3'-dideoxycytidine and recombinant interferon-alpha-A on replication of human...

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-alpha-A (rIFN-alpha-A) acts synergistically against HIV-1 replication in vitro. Various cell 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 assessed 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 cell toxicity. Synergism was seen at concentrations as low as 0.02 microM ddCyd plus 4 U of rIFN-alpha-A/mL or 0.01 microM ddCyd plus 8 U of rIFN-alpha-A/mL, whereas 10-fold higher concentrations were usually required to achieve similar effects with single drugs.