HIV drugs are expected to be Alzheimer’s disease

Drugs commonly used to treat HIV and hepatitis can have unexpected benefits: Prevent Alzheimer’s disease.

In a May 8 study published in Alzheimer’s and Dementia, researchers at the University of Virginia Health System found compelling evidence that nucleoside reverse transcriptase inhibitors (NRTIS) significantly reduce the risk of developing Alzheimer’s disease. The study analyzed health records of more than 270,000 patients in two major U.S. health insurance databases over 24 years and found that each year of NRTI treatment was associated with a 6-13% reduction in Alzheimer’s risk. These findings may change prevention strategies for diseases that affect millions of diseases around the world and demonstrate strong resistance to effective treatment.

The discovery offers new hope for new hope in challenging areas of Alzheimer’s disease research, with many promising treatments failing in late-stage clinical trials.

Beyond HIV treatment: New purposes for established drugs

NRTI has been the cornerstone of HIV treatment for decades, and it works by preventing the virus from replicating in the body. But the researchers found that these drugs have another valuable property – they inhibit inflammation, and protein complexes play a crucial role in the body’s immune response.

Dr. Jayakrishna Ambati, a research fellow at the UVA Center for Advanced Visual Science and Research, has previously identified this mechanism. His team suspects this may be related to Alzheimer’s disease, as inflammation is increasingly considered a key factor in disease progression.

“It is estimated that more than 10 million people around the world develop Alzheimer’s disease every year,” Ambati said. “Our results show that taking these drugs can prevent approximately 1 million new Alzheimer’s disease cases every year.”

Comprehensive analysis across different groups of people

The team analyzed two major health insurance databases: the Veterans Health Administration database, which mainly includes older male veterans and the MarketScan database, which represents a broader demographic scope of commercial insurers.

To ensure that their findings are strong, the researchers implemented several methodological assurances:

• Prone score matching to minimize selection bias between NRTI users and non-users
• Adjustments to nearly 20 different medical conditions known to affect Alzheimer’s risk
• Time-dependent analysis to illustrate changes in drug exposure
• Competitive risk model to address the possibility that mortality differences may be biased towards outcomes
• Separate analysis of HIV and hepatitis B patients to ensure that findings are not limited to a single disease

Even after these strict controls, the protection effects in both databases remain clear and consistent. In the Veterans Health Administration database, NRTI treatment is associated with a 6% reduction in the risk of developing Alzheimer’s disease every year. In the market scan database, this effect is even stronger, with a 13% reduction in the risk of treatment each year.

Inflammation: A key goal of Alzheimer’s disease

The findings of this study are linked to growing evidence that inflammation plays an important role in the development of Alzheimer’s disease. NLRP3 inflammasome – a protein complex associated with immune responses – is associated with the brain’s response to amyloid beta plaques and Tau Tangles, a hallmark physical feature of Alzheimer’s disease.

When these abnormal protein accumulation occurs, they may trigger the inflammasome, resulting in inflammatory responses that ultimately lead to neurodegeneration and cognitive decline. This creates a destructive cycle where inflammation causes more protein accumulation, triggering more inflammation.

The team’s findings suggest that by inhibiting inflammasome activation, NRTI may help break this cycle and prevent the development of Alzheimer’s disease.

Crucially, other types of HIV drugs do not inhibit inflammatory diseases (including non-NRTIS, protease inhibitors and integrase chain transfer inhibitors) do not show the same protective effect, thereby enhancing inflammatory inhibition as a key mechanism at work.

From database analysis to clinical trials

Although the findings of the study are promising, the researchers stress that database analysis cannot determine the establishment of causal relationships. To confirm protective effects and to determine the best treatment, clinical trials will be necessary.

However, there are some reasons for optimism. A small clinical trial of NRTI in Alzheimer’s disease is already underway, with a preliminary study of NRTI Lamivudine for 24 weeks, recently reporting a decrease in neurodegeneration and neuroinflammatory biomarkers.

Additionally, the UVA team has developed a potentially superior option. “We have also developed a new inflammatory disorder drug called K9, which is a safer and more effective version of NRTIS,” Ambati said. “This drug is already in clinical trials for other diseases and we plan to also test K9 for Alzheimer’s disease.”

While addressing some of its limitations, K9 maintains the inflammatory inhibitory properties of NRTI, such as potential mitochondrial toxicity and the risk of viral resistance due to long-term use. Preliminary tests in animal models showed encouraging results, with compounds reportedly reversing spatial memory and learning disabilities.

Important impact on public health

The potential public health impact of these findings is enormous. Almost 7 million Americans currently live with Alzheimer’s (that number is expected to be nearly double to 13 million by 2050), and effective prevention strategies may significantly reduce human and economic losses to the disease. In the United States alone, the annual cost of Alzheimer’s disease is expected to increase from $360 billion to nearly $1 trillion.

If clinical trials confirm the protective effect observed in this study, NRTI or its K9 (K9) derivatives may represent the prevention of Alzheimer’s disease, especially for high-risk individuals. The fact that these drugs have been approved by the FDA as other diseases may accelerate their implementation of Alzheimer’s disease prevention, although specific dosage regimens and safety profiles are needed for new uses to establish.

As researchers continue to explore the link between inflammasome inhibition and Alzheimer’s disease, the study adds to increasing awareness that targeting inflammation may represent one of the most promising pathways to combat this devastating disease.