UVA Health scientists have discovered that medications used to treat HIV may significantly reduce the risk of developing Alzheimer's disease, potentially preventing approximately one million new cases annually worldwide.
The research team, led by Dr. Jayakrishna Ambati, founding director of UVA's Center for Advanced Vision Science, found that patients taking nucleoside reverse transcriptase inhibitors (NRTIs) showed substantial protection against Alzheimer's disease. Their analysis of two major U.S. health insurance databases revealed that the risk of developing Alzheimer's decreased by 6% annually in one database and by 13% annually in the other for patients taking these medications.
"It's estimated that over 10 million people around the world develop Alzheimer's disease annually," said Dr. Ambati, who also holds the DuPont Guerry III Professorship in UVA's Department of Ophthalmology. "Our results suggest that taking these drugs could prevent approximately 1 million new cases of Alzheimer's disease every year."
The Science Behind the Protection
The protective effect appears to stem from the drugs' ability to block inflammasomes, important components of the immune system that have been implicated in Alzheimer's development. Dr. Ambati's team had previously identified this potential mechanism, which prompted them to investigate whether patients taking these medications showed reduced Alzheimer's risk.
NRTIs are primarily used to prevent HIV replication in the body, but their inflammasome-blocking properties may provide additional benefits beyond their intended use. Importantly, the researchers noted that patients taking other types of HIV medications did not show the same reduction in Alzheimer's risk, suggesting the effect is specific to NRTIs.
Comprehensive Data Analysis
To investigate this potential connection, the researchers analyzed 24 years of patient data from the U.S. Veterans Health Administration Database and 14 years from the MarketScan database of commercially insured patients. The former consists predominantly of male patients, while the latter offers a broader demographic representation.
The team identified more than 270,000 patients who were at least 50 years old and taking medications for either HIV or hepatitis B (another condition treated with NRTIs). After excluding patients with pre-existing Alzheimer's diagnoses and adjusting for potential confounding factors such as other medical conditions, the researchers confirmed that the reduction in Alzheimer's risk among NRTI users was both "significant and substantial."
Implications for Alzheimer's Prevention
The findings come at a critical time, as Alzheimer's rates continue to climb dramatically. Nearly 7 million Americans currently live with Alzheimer's, with projections suggesting this number could reach 13 million by 2050. The economic impact is equally concerning, with annual care costs potentially rising from $360 billion to almost $1 trillion, according to the Alzheimer's Association.
Based on their findings, the UVA researchers are now calling for clinical trials to test NRTIs' ability to prevent Alzheimer's disease.
"We have also developed a new inflammasome-blocking drug called K9, which is a safer and more effective version of NRTIs," Dr. Ambati explained. "This drug is already in clinical trials for other diseases, and we plan to also test K9 in Alzheimer's disease."
Next Steps in Research
The research team has published their findings in Alzheimer's & Dementia: The Journal of the Alzheimer's Association. The study was supported by the UVA Strategic Investment Fund, multiple National Institutes of Health grants, the DuPont Guerry III Professorship, and private donors.
If clinical trials confirm these observational findings, NRTIs or next-generation drugs like K9 could represent a significant breakthrough in Alzheimer's prevention. With the global burden of Alzheimer's disease expected to increase substantially in coming decades, repurposing existing medications or developing improved versions could provide a more rapid path to addressing this growing public health challenge.
The potential to prevent a million new cases annually would not only reduce human suffering but could also substantially mitigate the enormous economic burden associated with Alzheimer's care and treatment.
