Impact of Cocaine Abuse on HIV Pathogenesis

Over 1.2 million people in the United States are infected with the human immunodeficiency virus type 1 (HIV-1). Tremendous progress has been made over the past three decades on many fronts in the prevention and treatment of HIV-1 disease. However, HIV-1 infection is incurable and antiretroviral drugs continue to remain the only effective treatment option for HIV infected patients. Unfortunately, only three out of ten HIV-1 infected individuals in the US have the virus under control. Thus, majority of HIV-1 infected individuals in the US are either unaware of their infection status or not connected/retained to care or are non-adherent to antiretroviral therapy (ART). 

This national public health crisis, as well as the ongoing global HIV/AIDS pandemic, is further exacerbated by substance abuse, which serves as a powerful cofactor at every stage of HIV/AIDS including transmission, diagnosis, pathogenesis, and treatment. Clinical studies indicate that substance abuse may increase viral load, accelerate disease progression and worsen AIDS-related mortality even among ART-adherent patients. However, confirming a direct causal link between substance abuse and HIV/AIDS in human patients remains a highly challenging endeavor. 

In this review we will discuss the recent and past developments in clinical and basic science research on the effects of cocaine abuse on HIV-1 pathogenesis.

Below:  Schematic representation of the BBB. The BBB is made up of a continuous layer of tightly linked BMVECs. The BMVECs are supported by the basal lamina, followed by the brain parenchyma that consists of astrocytes, pericytes, perivascular macrophages, microglia, and neurons. Each component of BBB plays critical roles in maintaining the selective permeability of molecules for neuronal homeostasis and protecting the brain from pathogens and xenobiotics.

Below:  Effects of cocaine and HIV-1 on BBB integrity and neuronal toxicity. Cocaine and HIV-1 infection has been known to disrupt the integrity of BBB. This breach in BBB can increase trafficking of infected cells, viral particles and/or viral proteins into the brain causing systemic neuro-inflammation. Ongoing neuro-inflammation and low level of HIV-1 replication causes neuronal dysfunction and neurotoxicity. Furthermore, drugs of abuse such as cocaine can synergistically accentuate HIV associated neuronal dysfunction and neurotoxicity leading to worsening of HIV-1 neuropathogenesis.

Full article at: http://goo.gl/HGms9y

By: Sabyasachi Dash,^1,2 Muthukumar Balasubramaniam,^1,3 Fernando Villalta,^1,2,4 Chandravanu Dash,^1,2,3,* and Jui Pandhare^1,2,4,*

¹Center for AIDS Health Disparities Research, Meharry Medical College, Nashville, TN, USA

²School of Graduate Studies and Research, Meharry Medical College, Nashville, TN, USA

³Department of Biochemistry and Cancer Biology, Meharry Medical College, Nashville, TN, USA

⁴Department of Microbiology and Immunology, Meharry Medical College, Nashville, TN, USA

Edited by: Venkata S. R. Atluri, Florida International University, USA

Reviewed by: Nirupama Chandel, Feinstein Institute for Medical Research, USA; Prem L. Shama, Emory University School of Medicine, USA; Varghese George, University of Miami, USA

*Correspondence: Chandravanu Dash, ude.cmm@hsadc; Jui Pandhare, ude.cmm@erahdnapj

   

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