Can HIV Pills Prevent Alzheimer’s? Research Offers Hope

Promising Research on Current Medications

The ongoing search for effective methods to fight Alzheimer’s disease, a neurodegenerative disorder that steals millions of their memories and autonomy, has taken a potentially major turn. New research at the University of Virginia (UVA) indicates that current medications widely prescribed to treat HIV and hepatitis B, called nucleoside reverse transcriptase inhibitors (NRTIs), could provide significant protection against this debilitating disease. The results, which were released in the journal Alzheimer’s & Dementia, show that for every year that participants in the study were taking NRTI pills, their chances of getting Alzheimer’s went down by a significant amount.

This has caused a great deal of excitement in the medical community, with scientists estimating that these easily accessible drugs could prevent as many as a million new cases of Alzheimer’s each year worldwide. This possibility of repurposing current drugs highlights a cost-effective pathway toward addressing intricate diseases such as Alzheimer’s, possibly hastening the timeline toward preventative treatments versus the time-consuming development of completely new drugs. In addition, the sheer magnitude of the estimated prevention – one million cases per year globally – emphasizes the urgency and extreme significance of rigorously examining these preliminary findings, especially with the global population aging and dementia incidence increasing.

Substantial Decline in Alzheimer’s Risk with NRTI Use

The essence of the promising research is the substantial decline in Alzheimer’s risk found among those on NRTIs.The research carefully evaluated information from two large health insurance databases in the United States. The first set of data covered 24 years (2000-2024) from the U.S. Veterans Health Administration and included an enormous cohort of 11 million patients. Processing this data demonstrated that for every year of NRTI utilization, the probability of developing Alzheimer’s was reduced by 6%. The second set of data, spanning 14 years (2006-2020) of data from a privately insured patients database and involving 158 million individuals, demonstrated an even more significant decrease, with a 13% reduced risk of Alzheimer’s for every year of NRTI use. Significantly, this protective benefit held up even when the scientists took considerable care to adjust for a host of other factors that are known to increase the risk of developing Alzheimer’s in an individual.

The similarity of these results between two large and heterogeneous datasets, one largely of older male veterans and the other a more representative commercially insured population with a more even age and sex distribution, adds considerable credibility to the validity and possible generalizability of the findings. In addition, the trend seen towards increased risk reduction with increased duration of NRTI use also indicates a potential direct relationship between the drugs and the protective effect against Alzheimer’s.

Leadership and Call for Clinical Trials

At the helm of this pioneering research is Dr. Jayakrishna Ambati, the founding director of the University of Virginia Center for Advanced Vision Science. Highlighting the significant implications of their results, Dr. Ambati said that with more than 10 million new Alzheimer’s cases occurring worldwide annually, “our findings suggest that taking these drugs could prevent about 1 million new cases of Alzheimer’s disease each year.”.
Given these convincing results, Dr. Ambati and his research group are forcefully proposing the onset of clinical trials aimed at furthering and more assertively exploring NRTIs’ ability to preclude the advent of Alzheimer’s disease. The appeal for this action speaks well to the confidence the researchers hold in their outcome and the future possibility that NRTIs will be a measurable preventative measure for a disease in which there remain few effective measures.

Mechanism of Action: Acting on Inflammasomes.

The link between Alzheimer’s prevention and HIV medications is based on their mechanism of action.
NRTIs act primarily by inhibiting an enzyme named reverse transcriptase, which plays a central role in the replication of HIV in the body. Some common examples of NRTIs include tenofovir (sold under the brand names Viread and Vemlidy), entecavir (Baraclude), lamivudine (Epivir), abacavir (Ziagen), zidovudine (Retrovir), emtricitabine (Emtriva), and adefovir (Hepsera).
But Dr. Ambati’s group had already discovered something important: NRTIs can also inhibit the activation of inflammasomes. Inflammasomes are central proteins in the immune system of the body that are increasingly thought to be central to the pathogenesis of Alzheimer’s disease by initiating and perpetuating neuroinflammation. In Alzheimer’s disease, the beta-amyloid (Aβ) plaques and neurofibrillary tangles, made up of tau protein, the disease’s pathological features, are shown to trigger inflammasomes.

The process of activation triggers the release of pro-inflammatory cytokines, such as interleukin-1β (IL-1β) and IL-18, which further propagate neuroinflammation, are involved in causing neuronal damage, and eventually contribute to cognitive decline. Importantly, the NLRP3 inflammasome has also been recognized as a central molecular component of the neuroinflammatory pathway linked with Alzheimer’s. The increasing awareness of chronic neuroinflammation as a fundamental mechanism in the development of Alzheimer’s highlights the importance of determining drugs such as NRTIs that can significantly modulate this inflammatory process.

Study Methodology and Findings

To explore this possible connection between NRTIs and the risk of Alzheimer’s, the scientists used a large-scale retrospective cohort study. They carefully compared the above-given extensive health information from the U.S.   Veterans Health Administration and an insured patient database. They considered patients aged 50 and older who received NRTIs to treat HIV or hepatitis B and excluded patients with an earlier diagnosis of Alzheimer’s.
This strict method enabled them to define a large cohort of more than 270,000 patients fulfilling their research criteria. They followed these subjects forward in time and compared their Alzheimer’s diagnosis rates to the remainder of the patient populations across the databases. Key among these was using advanced statistical techniques to control for a broad range of other factors that might, in theory, affect a person’s chance of developing Alzheimer’s, e.g., age, sex, and prior medical conditions. The careful approach gives added confidence in the conclusion that the apparent lowering of Alzheimer’s risk was linked to the use of NRTIs.

Future Directions: Clinical Trials and Novel Drugs

Looking ahead, the research team is strongly recommending future, randomized clinical trials to conclusively determine if NRTIs can prevent Alzheimer’s disease, especially in people who do not have HIV or hepatitis B. Acknowledging the possible limitations of employing existing NRTIs, which were originally designed for viral infections and could have related side effects, Dr. Ambati’s team has also created a new drug named K9. K9 is engineered to be a more effective and safer inflammasome inhibitor. This precision design will optimize the anti-inflammatory effects while reducing off-target potential.

K9 is also in clinical trials for several other inflammatory diseases, such as Thyroid Eye Disease and geographic atrophy, a late stage of macular degeneration.
Encouragingly, preliminary results from a K8 trial (a similar molecule in the same class) have demonstrated a substantial slowing of lesion growth in patients with geographic atrophy. The researchers have lofty aspirations to also test the effectiveness of K9 for treating Alzheimer’s disease in future clinical trials.

The Growing Burden of Alzheimer’s Disease

The need for this research is highlighted by the vast and increasing burden of Alzheimer’s disease. Today, more than 7 million Americans have this condition. This figure is expected to almost double to roughly 13 million by 2050. The cost is also staggering, with the estimated cost of care for Alzheimer’s and other dementias in the United States expected to hit $384 billion in 2025 and perhaps skyrocket to almost $1 trillion by 2050. Alzheimer’s is not only a top cause of disability, but also a major cause of death among older people. In addition, the illness imposes a tremendous emotional and economic burden on families, with millions of caregivers giving unpaid care to their family members. The growing incidence and devastating effects of Alzheimer’s make it imperative for effective prevention and treatment measures to reduce this growing public health concern.

The results of this study provide a promising glimmer of hope in the fight against Alzheimer’s disease.
The implication that HIV drugs widely available today can provide a novel means of prevention, by interrupting the inflammatory processes involved in the onset of the disease, can fundamentally reshape the course of this destructive affliction in the future. Although these preliminary results from large-scale data analysis are promising, the authors correctly call attention to the fundamental necessity for prospective clinical trials to replicate these findings and determine the safety and efficacy of NRTIs for Alzheimer’s prevention in a wider population.

The parallel development and testing of more specific inflammasome inhibitors, such as K9, further attests to the dedication to discovering effective means to treat this disease. With the worldwide burden of Alzheimer’s increasing, the prospect of repurposing current medications and creating new, targeted therapies provides a welcome sense of optimism and clear direction for future research. The fact that this landmark research is published in a prestigious peer-reviewed journal lends additional validity to these promising results.   Data about NRTIs can be accessed easily through bodies such as the International Association of Providers of AIDS Care.

The findings of the study came from a University of Virginia news release on May 8, 2025.