Effects of RP 55778, a tumor necrosis factor alpha synthesis inhibitor, on antiviral activity of dideoxynucleosides

Antimicrob Agents Chemother. 1997 Apr;41(4):875-7. doi: 10.1128/AAC.41.4.875.

Abstract

Tumor necrosis factor alpha (TNF-alpha) is overexpressed during human immunodeficiency virus (HIV) infection. RP 55778, a TNF-alpha synthesis inhibitor, decreases HIV replication in monocytes/macrophages. Therapeutic use of RP 55778 in vivo, like that of other biological response modifiers, would theoretically require association with dideoxynucleosides. We have evaluated here the combinatory effects of zidovudine (AZT) or dideoxyinosine (ddI) and RP 55778. This TNF-alpha inhibitor antagonizes 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-HIV Agents / antagonists & inhibitors*
  • Anti-HIV Agents / pharmacology
  • Dideoxynucleosides / antagonists & inhibitors*
  • Dideoxynucleosides / pharmacology
  • HIV-1 / drug effects*
  • Humans
  • Microbial Sensitivity Tests
  • Pyridines / pharmacology*
  • Thiazoles / pharmacology*
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors*
  • Tumor Necrosis Factor-alpha / biosynthesis*
  • Virus Replication / drug effects
  • Zidovudine / antagonists & inhibitors
  • Zidovudine / pharmacology

Substances

  • Anti-HIV Agents
  • Dideoxynucleosides
  • Pyridines
  • Thiazoles
  • Tumor Necrosis Factor-alpha
  • Zidovudine
  • 3-(3-pyridinyl)-1H,3H-pyrrolo(1,2-c)thiazole-7-carboxamide