Profile of leukocyte-endothelial cell interactions induced in venules and arterioles by nucleoside reverse-transcriptase inhibitors in vivo

J Infect Dis. 2013 Nov 1;208(9):1448-53. doi: 10.1093/infdis/jit340. Epub 2013 Aug 1.


Background: There is controversy regarding cardiovascular (CV) toxicity of the nucleoside reverse-transcriptase inhibitors used to treat human immunodeficiency virus infection.

Methods: We evaluated the effects of nucleoside reverse-transcriptase inhibitors on leukocyte-endothelium interactions, a hallmark of CV diseases, in rat mesenteric vessels using intravital microscopy and in human arterial cells using a flow chamber system.

Results: Abacavir and didanosine increased rolling, adhesion and emigration in rat vessels. These effects were reversed with antibodies against Macrophage-1 antigen (Mac-1) or intercellular adhesion molecule 1 and were reproduced in human cells. Lamivudine, zidovudine, emtricitabine, and tenofovir had no effects.

Conclusions: Our results support the association of abacavir and didanosine with CV diseases.

Keywords: Abacavir; cardiovascular diseases; didanosine; emtricitabine; lamivudine; leukocyte-endothelium interations; tenofovir; zidovudine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-HIV Agents / pharmacology*
  • Arterioles / drug effects
  • Arterioles / pathology
  • CD11b Antigen / metabolism
  • CD18 Antigens / metabolism
  • Cell Adhesion
  • Cell Communication / drug effects
  • Cells, Cultured
  • Didanosine / pharmacology*
  • Dideoxynucleosides / pharmacology*
  • Endothelial Cells / drug effects*
  • Endothelium, Vascular
  • Humans
  • Intercellular Adhesion Molecule-1 / metabolism
  • Leukocyte Rolling / drug effects
  • Leukocytes, Mononuclear / drug effects
  • Leukocytes, Mononuclear / metabolism
  • Neutrophils / drug effects*
  • Neutrophils / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Reverse Transcriptase Inhibitors / pharmacology*
  • Venules / drug effects
  • Venules / pathology


  • Anti-HIV Agents
  • CD11b Antigen
  • CD18 Antigens
  • Dideoxynucleosides
  • Reverse Transcriptase Inhibitors
  • Intercellular Adhesion Molecule-1
  • Didanosine
  • abacavir