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Synergistic interaction between AZT and etoposide against HIV-1 infected HUT 78 cells.

Logan D, Filion LG, Izaguirre C, Conway B; International Conference on AIDS.

Int Conf AIDS. 1992 Jul 19-24; 8: 27 (abstract no. PuA 6101).

Ontario Cancer Treatment and Research Foundation, Univiversity of Ottawa, Canada.

OBJECTIVE: To determine if AZT could act in a synergistic manner with etoposide in controlling HIV-1 replication in T cells. METHODS Chronically infected HUT 78 cells were treated with AZT alone (1 microM), etoposide (0 to 100 micrograms/ml) or a combination of AZT and etoposide. The cultures were washed 24 hours later and recultured. Cell viability, morphology and p24 Ag levels were assessed 7 days later. RESULTS: Etoposide at all doses had a little or marginal effect in controlling HIV-1 replication in infected HUT 78 cells which had been infected for 24 hours prior to treatment. Similarly, AZT added to cultures for 24 hours only could not control HIV-1 replication in chronically infected HUT 78 cells. However, a synergistic interaction between AZT and various doses of etoposide was observed. Up to a 10 fold decrease in p24 Ag levels were observed in cultures with the combination therapy. Cell viability was not affected. DISCUSSION AND CONCLUSION: HIV-1 infects not only T cells but also cells of the mononuclear phagocytic system (MCPS). Anti-cancer drugs are employed with efficacy in the treatment of infectious Kaposi's sarcoma. Their mechanism of anti-tumour activity is unknown and possibly involves an indirect effect via antiviral activity. We have previously demonstrated that a 24 hour treatment of etoposide effectively control HIV-1 replication in acutely (1 day) or chronically (4 day) HIV-1 infected U937 cells. The conclusion from our experiments is that some anti-cancer drugs may be act synergistically with antiretroviral agents against HIV-1 replication. The mechanism of the synergistic interaction is not known but is being pursued.

Publication Types:
  • Meeting Abstracts
Keywords:
  • Anti-Retroviral Agents
  • Antiviral Agents
  • Etoposide
  • HIV-1
  • Sarcoma, Kaposi
  • Zidovudine
  • reverse transcriptase, Human immunodeficiency virus 1
Other ID:
  • 92404180
UI: 102201894

From Meeting Abstracts




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