Research Article Open Access

Cocaine: A Catalyst for Human Immunodeficiency Virus-Associated Dementia

Navneet K. Dhillon1, Milind Gadgil1, Andy Rahardja1, Shannon Callen1, Alex Sidelnik1, Duncan Renfrow1, Amanda Moradi1, Sukhbir Dhillon1, Himanshu Kenjale1, Anil Kumar1 and Shilpa J. Buch2
  • 1 University of Kansas Medical Center, United States
  • 2 University of Missouri Kansas City, United States

Abstract

Injection drug use has been recognized as a major risk factor for AIDS from the outset of the epidemic. Cocaine, one of the most widely abused drugs in the United States can both impair the functions of macrophages and CD4+ lymphocytes and also activate HIV-1 expression in these cells. Cocaine is a multifactorial agent that acts globally to impair the functioning of brain resident cells through multiple pathways. The drug not only promotes virus replication in macrophages, microglia and astrocytes, but can also upregulate CCR5 coreceptor, and reciprocally inhibit its ligands, thereby increasing virus infectivity. Cocaine is known to modulate astroglial function and activation. Cocaine causes a myriad of toxic responses in the neurons: a) it synergizes with viral proteins, Tat and gp120 resulting in exacerbated neuronal apoptosis, b) it causes calcium mobilization and, c) generation of reactive oxygen species. Additionally, cocaine also exerts potent effects on microvascular permeability, thereby impacting the influx of virus-infected inflammatory cells in brain parenchyma. By amplifying the various arms of the toxic responses that characterize HIV-associated dementia (HAD), cocaine skews the balance in favor of the virus leading to accelerated progression and severity of dementia.

American Journal of Infectious Diseases
Volume 4 No. 2, 2008, 131-139

DOI: https://doi.org/10.3844/ajidsp.2008.131.139

Published On: 30 June 2008

How to Cite: Dhillon, N. K., Gadgil, M., Rahardja, A., Callen, S., Sidelnik, A., Renfrow, D., Moradi, A., Dhillon, S., Kenjale, H., Kumar, A. & Buch, S. J. (2008). Cocaine: A Catalyst for Human Immunodeficiency Virus-Associated Dementia. American Journal of Infectious Diseases, 4(2), 131-139. https://doi.org/10.3844/ajidsp.2008.131.139

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Keywords

  • Cocaine
  • HIV
  • Transcription factors
  • Blood Brain Barrier