A novel method for the selective elimination of HIV infected cells: dexamethasone and procaine as a combination therapy prototype

UNCG Author/Contributor (non-UNCG co-authors, if there are any, appear on document)
Najoua Elbourakadi (Creator)
Institution
The University of North Carolina at Greensboro (UNCG )
Web Site: http://library.uncg.edu/
Advisor
Ethan Taylor

Abstract: It has been established that various combinations of three or more antiretroviral drugs will lead to durable inhibition of HIV replication in patients. Despite its success in controlling the infection, highly active antiretroviral therapy (HAART) does not eradicate the virus; systemic infection re-emerges upon treatment interruption in all but exceptional cases, necessitating a lifetime of expensive drug therapy with an ever-present risk of emerging drug resistance. Thus, there is a critical need for the development of new treatment modalities not based solely on virally-encoded targets, and with the potential to actually cure HIV infection. Using standard colorimetric and fluorometric live/dead cell labeling methods, we have developed a novel "selective cell death" assay, and identified a lead drug combination for elimination of infected cells, involving a patented combination of 2 generic FDA approved drugs or their metabolites: the glucocorticoid dexamethasone (Dex) and N,N-diethylaminoethanolamine (DEAE, a metabolite of procaine). Neither drug alone, but only the combination, is effective in cell killing, and only in HIV-infected cells (P<0.0001). Furthermore, prolonged exposure of cells to this drug combination leads to a decline in viral load; two weeks of treatment results in a decrease of more than 50% relative to untreated control cells. Flow cytometric methods indicate that the mechanism of infected cell death is via apoptosis. In addition, microray analysis has highlighted several host genes whose expression is altered by Dex/DEAE treatment, providing initial clues to understanding the pathways leading to apoptosis in infected cells.

Additional Information

Publication
Dissertation
Language: English
Date: 2011
Keywords
Antiretroviral drugs, HIV, Highly active antiretroviral therapy (HAART)
Subjects
HIV infections $x Treatment $x Research
Procaine $x Therapeutic use