UMD Researcher Receives $3.75M to Study Deadly Complication in HIV/AIDS Medications

Despite the wonders of anti-retroviral therapy (ART), which has changed an HIV /AIDS diagnosis from a likely death sentence to a manageable chronic condition for millions of patients, complications of the medication can pose serious risks, including a type of deadly brain inflammation known as immune reconstitution inflammatory syndrome (IRIS). 

Meiqing Shi, a professor in the University of Maryland Department of Veterinary Medicine has just received a $3.75 million, 5-year grant from the National Institutes of Health to study the cellular and molecular mechanisms underlying this lethal side effect. His work could translate into new strategies to treat IRIS, which occurs in an estimated 25 to 30% of HIV patients on ART. 

Shi studies how pathogens like certain fungi pass through the blood-brain barrier and infect the brain, one of the most protected organs in a mammal’s body. In addition, his lab has developed methods and mouse models that enable them to study how a host’s immune cells interact with the invading fungal pathogens and how those pathogens are cleared from the brain. 

In this project, he will apply his methods to understanding how IRIS occurs and how it may be better treated. The devastating syndrome is known to affect some patients starting anti-retroviral therapy who also have an infection from a fungus called cryptococcus. As their immune system begins to recover from the medication, immune cells can rapidly increase to attack the fungal infection and trigger a “cytokine storm” that causes severe inflammation in the brain. Although the infection itself may not be deadly, that inflammatory response can be fatal in up to 30% of cases.

“Successful completion of this study would gain novel insights into the cellular and molecular mechanisms that mediate lethal immune responses during cryptococcal IRIS and identify potential targets for treatment of HIV/AIDS-associated cryptococcal IRIS patients,” Shi said.