3-DRUG SYNERGISTIC INHIBITION OF HIV-1 REPLICATION INVITRO BY ZIDOVUDINE, RECOMBINANT SOLUBLE CD4, AND RECOMBINANT INTERFERON-ALPHA-A

Optimal management of human immunodeficiency virus type 1 (HIV-l) infections may require combinations of agents that attack different targets in the viral replicative cycle. Zidovudine (AZT), recombinant soluble CD4 (rsCD4), and recombinant interferon-alpha A (rIFN-αA) were evaluated in 2- and 3-drug regimens against HIV-l replication in vitro. Peripheral blood mononuclear cells and a CD4+T cell line (H9) were studied using multiple HIV-l replicative end points. Drug interactions were evaluated by the median-effect principle and the isobologram technique. AZT, rsCD4, and rIFN-αA inhibited HIV-l synergistically in 2- and 3-drug combinations. The 3-drug regimen provided more complete virus suppression than the 2-drug regimens. In H9 cells, single-drug regimens lost effectiveness at 10-14 days and 2-drug regimens lost effectiveness at 14-18 days. In contrast, the 3-drug regimen showed nearly complete suppression over 28 days in culture without toxicity. Clinical trials of these 3 drugs in combination should be considered. © 1990, University of Chicago. All rights reserved.