Synergistic Inhibition of Human Immunodeficiency Virus Type 1 (HIV-1) Replication In Vitro by Recombinant Soluble CD4 and 3'-Azido-3'-Deoxythymidine

Abstract

A combination of antiviral therapies that target different sites in the human immunodeficiency virus type 1 (HIV-1) replicative cycle may be necessary for optimal treatment of HIV-1 infections. We evaluated the interactions of a soluble virus receptor (recombinant soluble CD4 or rsT4) and a reverse transcriptase inhibitor (azidothymidine, AZT) against HIV-1 replication in vitro. A variety of cell types was studied including peripheral blood mononuclear cells, a CD4-positive T-cell line, and a CD4-positive human monocyte cell line. The combination of rsT4 and AZT inhibited HIV-1 synergistically over a broad range of drug concentrations and multiplicities of infection in several different HIV-1 replication assays. Drug interactions were evaluated by the median-effect principle and the isobologram technique using a computer analysis. In all of the cell types tested, combinations of rsT4 and AZT were synergistic in vitro, without additive cytotoxicity.