Abacavir Induces Arterial Thrombosis in a Murine Model

  • J Infect Dis. 2018 Jun 20;218(2):228-233. doi: 10.1093/infdis/jiy001.
Victor Collado-Diaz  1 ,  Isabel Andujar  2 ,  Ainhoa Sanchez-Lopez  1 ,  Samuel Orden  2 ,  María Amparo Blanch-Ruiz  1 ,  María Angeles Martinez-Cuesta  1  3 ,  Ana Blas-García  1  3 ,  Juan V Esplugues  1  2  3 ,  Ángeles Álvarez  1  3
Affiliations
  • 1. Departamento de Farmacología, Facultad de Medicina, Universidad de Valencia, Valencia, Spain.
  • 2. FISABIO-Fundación Hospital Universitario Dr Peset, Valencia, Spain.
  • 3. CIBERehd, Valencia, Spain.
PMID: 29346575 DOI: 10.1093/infdis/jiy001
Abstract

Background: The purinergic system is known to underlie prothrombotic and proinflammatory vascular programs, making the profile of experimental actions demonstrated by abacavir compatible with thrombogenesis. However, direct evidence of a prothrombotic effect by the drug has been lacking.

Methods: The present study appraised the effects of abacavir in a well-validated animal model of arterial thrombosis. The role of ATP-P2X7 receptors in the actions of the drug was also assessed, and the actions of recognized vascular-damaging agents and Other nucleoside reverse-transcriptase inhibitors (NRTIs) were evaluated and compared to those of abacavir.

Results: Abacavir dose-dependently promoted thrombus formation. This effect was reversed by a P2X7-receptor antagonist and was nonexistent in P2X7 knockout mice. The effects of abacavir were similar to those of diclofenac and rofecoxib. Other NRTIs had no thrombosis-related effects.

Conclusion: Abacavir promotes arterial thrombosis through interference with purinergic signaling, suggesting a possible biological mechanism for the clinical association of abacavir with cardiovascular diseases.

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