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J Infect Dis. 1990 Jun;161(6):1059-67.

Three-drug synergistic inhibition of HIV-1 replication in vitro by zidovudine, recombinant soluble CD4, and recombinant interferon-alpha A.

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Infectious Disease Unit, Massachusetts General Hospital, Boston, MA 02114.


Optimal management of human immunodeficiency virus type 1 (HIV-1) 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-alpha A) were evaluated in 2- and 3-drug regimens against HIV-1 replication in vitro. Peripheral blood mononuclear cells and a CD4+ T cell line (H9) were studied using multiple HIV-1 replicative end points. Drug interactions were evaluated by the median-effect principle and the isobologram technique. AZT, rsCD4, and rIFN-alpha A inhibited HIV-1 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.

[Indexed for MEDLINE]

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