A new $3.8 million grant will bring together clinical and bench researchers to better understand why individuals who receive anti-retroviral treatment for HIV are at greater risk for heart disease and stroke.
“The good news is that the drugs being used to fight HIV are increasing life expectancy to normal levels,” said University of Rochester neurologist Giovanni Schifitto, M.D., one of the co-leaders of the study. “However, one of the long-term complications is that these treatments, the infection itself, or a combination of the two are increasing risk for cardiovascular and cerebrovascular disease in this population.”
The study will bring together a multidisciplinary team of individuals with medical and engineering backgrounds, deploy new imaging technologies developed at the University of Rochester, and will involve a unique collaboration between clinical and basic science researchers.
People who undergo long-term anti-retroviral treatments for HIV often experience what doctors characterize as an accelerated aging process, particularly in their vascular system. This typically manifests itself in atherosclerosis, a hardening and narrowing of the arteries due to the accumulation of plaque and cellular degeneration. This condition puts patients at significantly greater risk for heart attacks and strokes.
Scientists speculate that this occurs due to some combination of the infection and the treatments themselves which may be damaging cells in the body’s blood vessels.
The study will follow 180 HIV positive and 90 negative individuals who are 50 years and older for three years. One of the key measures will be the thickness and stiffness of the carotid artery – the major blood vessel that serves the head and brain. The researchers will employ a new ultrasound technology developed by Marvin Doyley, Ph.D., with the University of Rochester Department of Electrical and Computer Engineering, to track changes to the vessel over time.
The project will also entail what is commonly referred to as “reverse translation.” In most instances, medical research is first conducted in the lab on cells and animals and these finding are then used to inform research in humans.
In this new study, the information gathered from the human volunteers will be employed by researchers in the lab to better understand the biological mechanism of the disease. Specifically, basic scientists will study cells from volunteers in order to test a theory that the anti-retroviral treatments may be activating proteins that are causing inflammation in the cells and contributing the onset of arterial sclerosis. The researchers will then further probe these findings in an animal model so that new preventive therapies can be tested.
“While the comprehensive approach of this study seems like common sense, it is not as common as one might think,” said Sanjay B. Maggirwar, M.B.A., Ph.D., a professor in the University of Rochester Department of Microbiology and Immunology and a co-leader of the study. “By observing this condition in humans while at the same time conducting the basic research necessary to understand the series of events at the cellular level that lead to premature vascular aging, we can more rapidly translate these findings into potential new therapeutic approaches.”
The researchers expect to begin enrolling study volunteers later this month.
The study is being funded by the National Heart, Lung and Blood Institute. The research team will also consist of Jun-Ichi Abe with M.D. Anderson Cancer Center in Texas, and Vikram Dogra, Amneris Luque, and Xing Qiu with the University of Rochester.