Inhibition of Human Immunodeficiency Virus Type 1 Replication In Vitro by the Bisheteroarylpiperzine Atevirdine (U-87201E) in Combination with Zidovudine or Didanosine

Thomas B. Campbell*, Russell K. Young, Joseph J. Eron, Richard T. D’Aquila, W. Gary Tarpley, Daniel R. Kuritzkes

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

22 Scopus citations

Abstract

The bisheteroarylpiperazine nonnucleoside reverse transcriptase (RT) inhibitor atevirdine effectively inhibits human immunodeficiency virus type 1 (HIV-1) in vitro. Clinical isolates with a wide range of 50% inhibitory concentrations (IC50s) of zidovudine (IC50, 0.003 to >2.0 µM) and didanosine (IC50, 0.02 to > 10.0µM) were inhibited by atevirdine (median IC50, 0.74µM; range, 0.06-1.60). Cross-resistance to atevirdine in zidovudine- or didanosine-resistant isolates was not observed. Combinations ofatevirdine and zidovudine were highly synergistic against zidovudineresistant clinical isolates of HIV-1. By contrast, these combinations were mostly additive when tested against zidovudine-susceptible isolates. Combinations of atevirdine and didanosine were additive in their effects against both didanosine-susceptible and -resistant isolates. These data suggest that the interaction of atevirdine with HIV-1 RT is different than that of other nonnucleoside RT inhibitors and that combinations of atevirdine and zidovudine may be useful in patients with AIDS who have initially received monotherapy with zidovudine.

Original languageEnglish (US)
Pages (from-to)318-326
Number of pages9
JournalJournal of Infectious Diseases
Volume168
Issue number2
DOIs
StatePublished - Aug 1993

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases

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