$2.8 Million NIH R01 Grant Supports Multisite Study on Cardiovascular Risk in HIV
Chronic inflammation is a bad actor across many health and medical conditions, but for people living with HIV, it can be particularly dangerous. People with HIV are at elevated risk for multiple adverse cardiovascular outcomes, including stroke, heart failure and clotting of the blood vessels. Heart attacks, sometimes fatal, can also strike people with HIV as early as in their 20s and 30s.
For a long time, it wasn’t clear why.
Now, armed with a $2.8 million R01 grant from the National Heart, Lung, and Blood Institute (NHLBI), a multi-study led by Claudia Martinez, M.D., professor of clinical medicine in the Cardiovascular Division at the University of Miami Miller School of Medicine, researchers will look deeper into what is driving this elevated risk.
The novel four-year study will examine factors on the surface of body cells that react when HIV or certain other viruses invade them. These factors are a type of lipids, called eicosanoids, that mediate inflammation.
“The hope is to identify targets that will help decrease inflammation in its tracks, reducing cardiovascular disease — the number one cause of death in this population today,” said Dr. Martinez, the study’s principal investigator, who will work with a team of collaborators at Mount Sinai School of Medicine in New York City, the University of Washington in Seattle, and the University of California at San Francisco (UCSF) and San Diego (UCSD).
“No one has really looked into this,” Dr. Martinez said, in part because the ability to measure the eicosanoid activity is a recent advance.
The presence of HIV skews an important balance “between the good and the bad inflammatory components that are trying to eliminate the virus,” Dr. Martinez said. At the same time, the virus triggers a chronic inflammatory state linked to heart attacks and other bad outcomes.
“It’s an honor to be one of the NIH’s select researchers to receive funding to study cardiovascular disease among people with HIV.”
The R01 grant reflects the University’s research reputation with the National Institutes of Health (NIH) and the NHLBI, she said.
Miller School at the Forefront of HIV Research
As South Florida remains the epicenter of the HIV epidemic, the Miller School is uniquely positioned to study various aspects of the disease. One of the 19 NIH Centers for AIDS Research (CFAR) institutions nationwide, the school also is now part of the largest cohorts of people with HIV. This CFAR Network of Integrated Clinical Systems (CNICS) cohort includes blood samples from more than 10,000 people with HIV.
The first aim will be to profile eicosanoids in about 3,000 blood samples from people with and without HIV. Data for the control group will come from previous large studies. A second aim is to identify genetic loci associated with elevated eicosanoids and higher cardiovascular risk; a third is to conduct multiomic research including genomics, lipidomics, proteomics and metabolomics.
As a cardiologist, Dr. Martinez is reviewing all the medical charts to verify heart conditions and heart attack outcomes.
“It’s really a demonstration of large-scale collaboration,” Dr. Martinez said. She orchestrated the participating researchers based on their expertise. Blood samples will be analyzed at UCSD and genomics will be performed at Mount Sinai, for example.
“The quality of investigators that we have is amazing. The network of collaboration is very strong,” Dr. Martinez said. The Miller School “is also the site for many very important national studies with large cohorts of people living with HIV.”
Inflammation in the Bigger Picture
In summer 2022, Dr. Martinez received a $2.3 million Avenir Award from the National Institute on Drug Abuse to study the impact of cannabis use and heart health among people with HIV.
“This project is in the same line of research,” she said. “We are looking for specific contributors, like inflammatory pathways, to heart disease in people with HIV.”
The research could have larger implications. “The interesting thing, even though we are specifically looking at HIV, is this is relevant for everyone because it is an example of how inflammation affects the heart,” Dr. Martinez said. “HIV is a trigger in this case, but it could be a different virus.”
The ultimate goal of the study is to identify therapeutic targets to block this inflammatory process. If successful, Dr. Martinez and colleagues will have found a possible life-saving way to reduce this elevated risk for cardiovascular outcomes in people with HIV.
Adam Carrico, Ph.D., associate professor in the Department of Public Health Sciences, is a co-investigator. Other researchers include co-principal investigator Inga Peter, Ph.D., at Mount Sinai School of Medicine in New York City; Heidi Crane, M.D., M.P.H., at the University of Washington; Peter Hunt, M.D., at UCSF; and Mohit Jain, M.D., Ph.D., and Mona Alotaibi, M.D., at UCSD.