Researchers Track Link Between Anti-HIV Drugs and Body Fat Changes

Carle Illinois College of Medicine researchers are leading efforts to discover why long-term users of anti-HIV drugs are prone to weight gain and other fat-related health complications. The answers may lead to safer care for patients living with HIV, improved drug regimens for those using anti-HIV drugs for prevention, and new insights into cell-based treatments for inflammatory conditions that are prevalent in aging.

Over the past 30 years, the use of combined antiretroviral medications has saved the lives of millions of patients infected with HIV. But as these drugs have evolved, studies have revealed that many patients also develop long-term complications, including unwanted weight gain, fat loss or buildup in various parts of the body, and fat that becomes inflamed and accumulates around the heart and other organs. 

“Because millions of people worldwide take these medications for life, understanding their long-term effects on fat is a public health priority."

Bunnell leads a new federally funded study probing changes in fat cells associated with long-term antiretroviral use. “We want to answer a deceptively simple question: how much of this fat-tissue damage is caused by the HIV itself, how much is caused by the long-term use of the anti-HIV drugs, and how much only appears when the two work together?” 

Mapping fat dysfunction 

With support from a $4.16M grant from the National Institutes of Health, Bunnell’s lab will spend the next several years tracking alterations in fat cells and measuring functional changes associated with extended anti-HIV drug exposure. He says fat-related dysfunction carries broad, long-term health implications for the HIV-positive population, especially as they age.

“Fat is not just passive storage; it is a metabolically active organ that talks to the immune system, the heart, and the whole body,” Bunnell said. “When fat becomes damaged or inflamed, it drives a cascade of problems: type 2 diabetes, high cholesterol, heart disease, and a phenomenon called ‘inflammaging’—accelerated, inflammation-driven aging. People living with HIV develop these conditions earlier and more severely than the general population.” 

The research team combines Bunnell’s expertise in stem cell research with HIV, imaging, and pathology expertise from partners at Tulane National Biomedical Research Center in New Orleans. Together, they will leverage cutting-edge technology to study HIV-related fat cell disruptions in animal models over time and reveal how long-term use of anti-HIV drugs impacts fat cells. 

“The project combines CT imaging to track fat distribution in the body, spatial transcriptomics to map gene activity cell by cell within intact tissue, AI-driven digital pathology, and flow cytometry of live cells obtained by biopsy,” Bunnell said. 

The research will explore the effects of antiretroviral drug combinations that are already approved and widely used, making the results useful to clinicians in improving care strategies for people who use anti-HIV medications.

“By pinpointing which specific drugs damage fat cells and how, clinicians and drug developers can design regimens that control the virus without harming metabolic health,” Bunnell said. The team’s findings could also provide new guidance for improved medication regimens for HIV-negative people who use anti-HIV drugs for infection prevention.

Solutions beyond HIV care

Bunnell foresees broader application of the research, possibly fueling discoveries that could benefit other patient populations.

Many of the same processes — inflamed fat, damaged stem cells, and accelerated aging — are also central to ordinary obesity, type 2 diabetes, and normal aging,” he said. 

Through Bunnell’s research lab and the new Translational Oncology and Regenerative Medicine Laboratory clean room, CI MED is becoming a leader in regenerative medicine. This growing field of science and healthcare focuses on helping the body repair, replace, or regrow damaged cells, tissues, and organs rather than simply treating symptoms. 

“My group has spent years defining how these cells grow, differentiate, and behave under stress,” Bunnell said. “Extending that expertise to a real-world clinical problem — HIV-associated fat dysfunction — connects fundamental stem-cell science to human disease in a way central to the CI MED mission of engineering-driven medicine.”