CHARLOTTESVILLE, Va. — A new study from UVA Health suggests that a class of HIV medications known as nucleoside reverse transcriptase inhibitors (NRTIs) may significantly reduce the risk of developing Alzheimer’s disease, prompting calls for clinical trials to explore their preventative potential.
The research, led by Dr. Jayakrishna Ambati of the University of Virginia School of Medicine, analyzed health data from more than 270,000 patients and found that those taking NRTIs were substantially less likely to develop Alzheimer’s. In one national database, the annual risk reduction was 6%; in another, it reached 13%.
“It’s estimated that over 10 million people around the world develop Alzheimer’s disease annually,” said Ambati, founding director of UVA’s Center for Advanced Vision Science. “Our results suggest that taking these drugs could prevent approximately 1 million new cases of Alzheimer’s every year.”
NRTIs are commonly used to prevent replication of the HIV virus, and also to treat hepatitis B. However, earlier research by Ambati’s team revealed that these medications may block inflammasomes—proteins in the immune system believed to play a role in Alzheimer’s disease development.
To test this theory, the team conducted a retrospective analysis using two major U.S. health insurance databases: the U.S. Veterans Health Administration database, which primarily includes male patients, and the MarketScan database, which provides a broader demographic sample. They reviewed 24 and 14 years of data, respectively, focusing on patients aged 50 and older who were prescribed NRTIs and had no prior diagnosis of Alzheimer’s.
After adjusting for variables such as underlying medical conditions, researchers concluded that the risk reduction associated with NRTIs was “significant and substantial.”
Importantly, patients who took other types of HIV medications did not exhibit the same decreased risk, strengthening the case for NRTIs as a unique therapeutic candidate.
With Alzheimer’s cases projected to double in the U.S. by 2050—from nearly 7 million today to 13 million—the potential for repurposing existing HIV medications offers a promising avenue for prevention. The cost implications are also stark, with the annual care burden expected to rise from $360 billion to nearly $1 trillion, according to the Alzheimer’s Association.
In addition to exploring the effects of current NRTIs, Ambati’s team has developed a new inflammasome-inhibiting drug, dubbed K9. The medication, described as a safer and more effective alternative to traditional NRTIs, is already undergoing clinical trials for other diseases. Plans are in place to test its efficacy against Alzheimer’s as well.
“Our findings highlight a potential new way to reduce the global burden of Alzheimer’s,” Ambati said. “It’s time to put these drugs to the test in dedicated clinical trials.”
