THALIDOMIDE INHIBITS THE REPLICATION OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1

Thalidomide, a selective inhibitor of tumor necrosis factor alpha (TNF -alpha) synthesis, suppresses the activation of latent human immunodef iciency virus type 1 (HIV-1) in a monocytoid (U1) line. The inhibition is dose dependent and occurs after exposure of the cells to recombina nt TNF-alpha, phorbol myristate acetate, lipopolysaccharide, and other cytokine combinations. Associated with HIV-1 inhibition is a reductio n in agonist-induced TNF-alpha protein and mRNA production. Thalidomid e inhibition of virus replication in the phorbol myristate acetate- an d recombinant TNF-alpha-stimulated T-cell line ACH-2 is not observed. The presence of thalidomide also inhibits the activation of virus in t he peripheral blood mononuclear cells of 16 out of 17 patients with ad vanced HIV-1 infection and AIDS. These results suggest the use of thal idomide in a dinical setting to inhibit both virus replication and the TNF-alpha-induced systemic toxicity of HIV-1 and opportunistic infect ions.