HIV in the United States has become a manageable disease, thanks to the free and wide accessibility of antiretroviral therapy. Antiretrovirals work by preventing the virus from making copies of itself by blocking stages of its life cycle. But these drugs have poor permeability in the brain. HIV replication persists in brain cells, causing HIV-associated neurocognitive disorders. Additionally, the HIV population is aging. More than 50% of the HIV population in the U.S. will soon reach their 60s, the prime decade when Alzheimer’s disease symptoms begin to manifest. The coupling of these factors have made it critically important to examine the relationship between HIV-induced aging and Alzheimer’s disease.
A team at the University of Tennessee Health Science Center has taken on this challenge, with the help of a $423,500 grant from the National Institute on Aging. Santosh Kumar, PhD, professor in the Department of Pharmaceutical Sciences, and Tauheed Ishrat, PhD, professor in the Department of Anatomy and Neurobiology, are working to define the underlying mechanisms contributing to Alzheimer’s disease-associated neurodegeneration and memory impairment in the HIV population. Their project involves developing a new drug delivery system and regimens to facilitate drug permeability to the brain. Increased HIV suppression in the brain will subsequently decrease HIV-associated neurocognitive disorder, aging, and Alzheimer’s disease-related pathology.
“Our research goal is to better manage cognitive decline and Alzheimer’s disease pathologies in HIV/AIDS populations who are aging,” Dr. Kumar said.
The specific research will focus on how novel extracellular vesicles carry specific molecules, including viral proteins, from HIV-infected brain cells and deliver them to neuronal cells. The team hypothesizes that delivery of these vesicles causes a cascade of cellular events that ultimately bring about neuroinflammation and neurodegeneration. The team will also use these extracellular vesicles to carry antiretroviral drugs permeable to brain to suppress brain HIV.