Synergistic combinations of the CCR5 inhibitor VCH-286 with other classes of HIV-1 inhibitors

Antimicrob Agents Chemother. 2014 Dec;58(12):7565-9. doi: 10.1128/AAC.03630-14. Epub 2014 Sep 29.

Abstract

Here, we evaluated the in vitro anti-HIV-1 activity of the experimental CCR5 inhibitor VCH-286 as a single agent or in combination with various classes of HIV-1 inhibitors. Although VCH-286 used alone had highly inhibitory activity, paired combinations with different drug classes led to synergistic or additive interactions. However, combinations with other CCR5 inhibitors led to effects ranging from synergy to antagonism. We suggest that caution should be exercised when combining CCR5 inhibitors in vivo.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-HIV Agents / metabolism
  • Anti-HIV Agents / pharmacology*
  • Clinical Trials as Topic
  • Cyclohexanes / metabolism
  • Cyclohexanes / pharmacology*
  • Drug Antagonism
  • Drug Combinations
  • Drug Synergism
  • Gene Expression
  • HIV-1 / drug effects*
  • HIV-1 / enzymology
  • HIV-1 / genetics
  • Humans
  • Leukocytes, Mononuclear / drug effects
  • Leukocytes, Mononuclear / virology
  • Maraviroc
  • Microbial Sensitivity Tests
  • Piperazines / metabolism
  • Piperazines / pharmacology*
  • Pyrimidines / metabolism
  • Pyrimidines / pharmacology*
  • Receptors, CCR5 / genetics
  • Receptors, CCR5 / metabolism*
  • Reverse Transcriptase Inhibitors / metabolism
  • Reverse Transcriptase Inhibitors / pharmacology*
  • Spiro Compounds / metabolism
  • Spiro Compounds / pharmacology*
  • Triazoles / metabolism
  • Triazoles / pharmacology*
  • Tropanes / metabolism
  • Tropanes / pharmacology*
  • Virus Replication / drug effects

Substances

  • Anti-HIV Agents
  • CCR5 protein, human
  • Cyclohexanes
  • Drug Combinations
  • Piperazines
  • Pyrimidines
  • Receptors, CCR5
  • Reverse Transcriptase Inhibitors
  • Spiro Compounds
  • Triazoles
  • Tropanes
  • VCH-286
  • Maraviroc
  • vicriviroc