P. Clayette et al., EFFECTS OF RP-55778, A TUMOR-NECROSIS-FACTOR-ALPHA SYNTHESIS INHIBITOR, ON ANTIVIRAL ACTIVITY OF DIDEOXYNUCLEOSIDES, Antimicrobial agents and chemotherapy, 41(4), 1997, pp. 875-877
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.