Cocaine: A Catalyst for Human Immunodeficiency Virus-Associated Dementia
Navneet K. Dhillon, Milind Gadgil, Andy Rahardja, Shannon Callen, Alex Sidelnik, Duncan Renfrow, Amanda Moradi, Sukhbir Dhillon, Himanshu Kenjale, Anil Kumar and Shilpa J. Buch
DOI : 10.3844/ajidsp.2008.131.139
American Journal of Infectious Diseases
Volume 4, Issue 2
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.
© 2008 Navneet K. Dhillon, Milind Gadgil, Andy Rahardja, Shannon Callen, Alex Sidelnik, Duncan Renfrow, Amanda Moradi, Sukhbir Dhillon, Himanshu Kenjale, Anil Kumar and Shilpa J. Buch. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.