Scientists have discovered a potential connection between commonly used HIV medications and a lower risk of developing Alzheimer’s disease. The current number of people affected by Alzheimer’s in the U.S. is nearly seven million, and it is expected to increase to almost 13 million by 2050. The lack of effective treatments for the disease is a significant medical challenge. Researchers at Sanford Burnham Prebys have found promising real-world associations between common HIV drugs and a reduced incidence of Alzheimer’s disease. The study, led by Jerold Chun, M.D., Ph.D., was published in Pharmaceuticals.The research expands on the previous findings published in Nature in 2018, which explained how gene recombination in neurons can generate numerous new gene variants in Alzheimer’s disease brains. The study also uncovered that the Alzheimer’s-related gene, APP, undergoes recombination using the same enzyme found in HIV, known as reverse transcriptase (RT).
This enzyme is responsible for copying RNA molecules and converting them into complementary DNA duplicates, which can then be inserted back into DNA, resulting in permanent sequence changes within the cell’s DNA blueprint.
HIV and various other viruses depend on RT to take over the host cell’s genetic material.Check out a host’s cells to develop a long-term infection, so medications that prevent the RT enzyme’s activity have become a common part of treatment cocktails for managing HIV.
The brain seems to have its own RTs that differ from those in viruses, and the research team questioned if blocking brain RTs with HIV drugs actually benefits AD patients.
Looking at the connection between real-world RT inhibitor exposure and AD in humans, the team examined anonymous medical records with prescription claims from over 225,000 control and HIV-positive patients, and discovered that RT inhibitor exposure was linked to a statistically significant association.The study found a reduced occurrence of Alzheimer’s disease in HIV-positive individuals taking RT inhibitors and other combined antiretroviral therapies as they aged. The researchers examined over 225,000 individuals with claims data, including nearly 80,000 HIV-positive individuals over the age of 60. Of those, more than 46,000 had taken RT inhibitors during a three-year observation period from 2016 to 2019. The results showed a significantly lower incidence of Alzheimer’s disease in this group compared to the general population. Lead researcher Chun stated, “The answer is that there were many fewer than might have been expected compared to the general population.”Collaborating with health information technology and clinical research firm IQVIA, led by Tiffany Chow, M.D.
Among individuals living with HIV, there were 2.46 diagnoses of Alzheimer’s disease per 1,000 people for those taking these inhibitors, compared to 6.15 for the general population. This comparison group consisted of over 150,000 HIV-negative patients over 60 years old with medical insurance claims for treatment of the common cold.
“Running a prospective clinical trial with this many patients is not feasible,” Chun explains. “This method allows us to examine how a drug can act on a large patient population.”
Chun emphasizes that the medications taken by patients in this retrospective study were specifically made to counter the activity of RT in HIV and likely only had a limited impact on the various forms of the enzyme active in the brain.
“What we are examining at the moment is very basic,” Chun states. “The next step for our research team is to identify which versions of RTs are present in the AD brain so that more specific treatments can be developed. Additionally, clinical trials of currently available RT inhibitors on individuals with early AD should be pursued.”
Jerold Chun, M.D. Ph.D., holds the position of professor in.The research was conducted at the Center for Genetic Disorders and Aging Research at Sanford Burnham Prebys. Tiffany W. Chow, Mark Raupp, Matthew W. Reynolds, Siying Li, and Gwendolyn E. Kaeser were also involved in the study. Funding was provided by the National Institute on Aging — NIH, the Shaffer Family Foundation, and the Bruce Ford & Anne Smith Bundy Foundation. The journal reference for the study is Tiffany W. Chow, Mark Raupp, Matthew W. Reynolds, Siying Li, Gwendolyn E. Kaeser, Jerold Chun. Nucleoside Reverse Transcriptase In.A recent study published in Pharmaceuticals found that exposure to a certain type of inhibitor is linked to a lower risk of Alzheimer’s disease. The study, titled “Inhibitor Exposure Is Associated with Lower Alzheimer’s Disease Risk: A Retrospective Cohort Proof-of-Concept Study,” provides important evidence for the potential benefits of this type of exposure. The study, which was a retrospective cohort proof-of-concept study, is a significant step in understanding the potential impact of inhibitor exposure on Alzheimer’s disease risk. This research has the potential to inform future studies and interventions for Alzheimer’s disease.
