EFFECTS OF RP-55778, A TUMOR-NECROSIS-FACTOR-ALPHA SYNTHESIS INHIBITOR, ON ANTIVIRAL ACTIVITY OF DIDEOXYNUCLEOSIDES

Tumor necrosis factor alpha (TNF-alpha) is overexpressed during human immunodeficiency virus (HIV) infection. RP 55778, a TNF-alpha synthesi s inhibitor, decreases HIV replication in monocytes/macrophages. Thera peutic use of RP 55778 in vivo, like that of other biological response modifiers, would theoretically require association with dideoxynucleo sides. We have evaluated here the combinatory effects of zidovudine (A ZT) or dideoxyinosine (ddI) and RP 55778. This TNF-alpha inhibitor ant agonizes the antiviral effects of both dideoxynucleosides, especially AZT. The more favorable anti-HIV activity of ddI in resting cells may explain these unequal degrees of antagonism.