Scientists at the University of Virginia (UVA) Health are advocating for clinical trials to explore the potential of HIV drugs, specifically nucleoside reverse transcriptase inhibitors (NRTIs), in preventing Alzheimer’s disease. This call to action follows their finding that patients taking these medications exhibit a significantly reduced likelihood of developing the debilitating memory condition.

The research,spearheaded by Dr. Jayakrishna Ambati, MD, at UVA, builds upon previous findings that identified a possible mechanism through which these drugs could offer protection against Alzheimer’s. This promising lead prompted an analysis of two major health insurance databases in the United States to assess Alzheimer’s risk among patients prescribed NRTIs. The results were compelling: one database showed a 6% annual decrease in Alzheimer’s risk for each year patients were on the drugs, while the other indicated a 13% annual decrease.

The Potential Impact

The implications of these findings are considerable, considering the global burden of Alzheimer’s disease.

It’s estimated that over 10 million people around the world develop alzheimer’s disease annually. Our results suggest that taking these drugs could prevent approximately 1 million new cases of Alzheimer’s disease every year.
Dr. Jayakrishna Ambati,MD,Founding director of UVA’s Center for Advanced Vision Science

Dr. Ambati is the DuPont Guerry III Professor in the School of Medicine’s Department of Ophthalmology.

How NRTIs May Protect the brain

NRTIs are primarily used to inhibit the replication of the HIV virus within the body. However, Dr. Ambati and his team discovered that these drugs can also prevent the activation of inflammasomes, which are crucial components of the immune system. These inflammasomes have been linked to the development of Alzheimer’s disease. Therefore, the researchers hypothesized that patients taking NRTIs might be less susceptible to developing Alzheimer’s.

To investigate this, the researchers examined patient data spanning 24 years from the U.S.Veterans Health Administration Database, which predominantly consists of male patients, and 14 years from the MarketScan database of commercially insured patients, offering a more diverse population sample. They focused on individuals aged 50 and older who were taking medications for HIV or hepatitis B, both of which are treated with NRTIs, while excluding those with a prior Alzheimer’s diagnosis.

Analyzing the Data

The study encompassed over 270,000 patients who met the specified criteria. The researchers analyzed the incidence of Alzheimer’s development within this cohort. Even after accounting for potential confounding factors, such as pre-existing medical conditions, the team concluded that the reduction in Alzheimer’s risk among patients on NRTIs was significant and substantial, as detailed in their published scientific paper.

The Need for Clinical Trials

The researchers emphasized that patients taking other types of HIV medications did not exhibit the same reduction in Alzheimer’s risk as those on NRTIs. This observation strengthens the case for clinical trials to rigorously evaluate the potential of nrtis in preventing Alzheimer’s disease.

The Looming Alzheimer’s Crisis

The urgency for effective Alzheimer’s prevention strategies is underscored by the disease’s escalating prevalence and associated costs. The Alzheimer’s Association projects that the number of Americans living with Alzheimer’s will surge to 13 million by 2050. Moreover, the annual cost of care for Alzheimer’s and other dementias could skyrocket from $360 billion to nearly $1 trillion.

A New Hope: The K9 Drug

In addition to exploring the potential of existing NRTIs, Dr. Ambati’s team is also developing a novel inflammasome-blocking drug.

We have also developed a new inflammasome-blocking drug called K9, which is a safer and more effective version of NRTIs. This drug is already in clinical trials for other diseases, and we plan to also test K9 in Alzheimer’s disease.
Dr. Jayakrishna Ambati, MD, Founding Director of UVA’s Center for Advanced Vision Science

Reference

Magagnoli J, Ambati M, Cummings TH, et al. Association of nucleoside reverse transcriptase inhibitor use with reduced risk of Alzheimer’s disease risk. Alzheimers Dement. 2025;21(5):e70180. doi: 10.1002/alz.70180