Ganciclovir antagonizes the anti-human immunodeficiency virus type 1 activity of zidovudine and didanosine in vitro

D. J. Medina, G. D. Hsiung, J. W. Mellors

Research output: Contribution to journalComment/debatepeer-review

32 Scopus citations

Abstract

In studies examining potential interactions between ganciclovir (GCV) and either zidovudine (AZT) or didanosine (DDI) in H9 cells, GCV was found to consistently reduce the anti-human immunodeficiency virus type 1 potency of both AZT and DDI. In the presence of GCV, the 50% effective doses of AZT and DDI were increased three- to sixfold, depending on the molar ratio of drugs and the measure of human immunodeficiency virus type 1 replication (p24 antigen, reverse transcriptase activity, or infectious virus yield). Multiple dose-effect analysis revealed strong antagonism between GCV and either AZT or DDI (combination indices, 2.2 to 6.7). This antagonistic effect occurred at drug concentrations that were well below the cytotoxic range. At higher drug concentrations, the combination of GCV and AZT was synergistically cytotoxic (combination indices, <1.0), whereas GCV and DDI were only additively cytotoxic (combination indices, ca. 1.0). Thus, the combination of GCV with AZT or DDI may result in antiviral antagonism and either synergistic (AZT- GCV) or additive (DDI-GCV) cytotoxicity.

Original languageEnglish (US)
Pages (from-to)1127-1130
Number of pages4
JournalAntimicrobial agents and chemotherapy
Volume36
Issue number5
DOIs
StatePublished - 1992

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Pharmacology (medical)
  • Infectious Diseases

Fingerprint

Dive into the research topics of 'Ganciclovir antagonizes the anti-human immunodeficiency virus type 1 activity of zidovudine and didanosine in vitro'. Together they form a unique fingerprint.

Cite this