Common HIV medications are associated with a reduced risk of Alzheimer's disease

Common HIV medications are associated with a reduced risk of Alzheimer's disease

Alzheimer's disease (AD) currently affects nearly seven million people in the United States. By 2050, that number is expected to rise to nearly 13 million. The lack of useful treatments represents a major unmet medical need. Scientists at Sanford Burnham Prebys have now identified promising real-world links between common HIV medications and reduced AD incidence. The Jerold Chun, MD, Ph.D. led study was published indrug.

Chun's new research builds on his lab's groundbreaking publicationNatureIn 2018, it was described how recombination of somatic genes in neurons can produce thousands of new gene variants in the brains of Alzheimer's patients. Importantly, it has also been shown for the first time how the Alzheimer's disease-related gene, APP, is recombined using the same type of enzyme found in HIV.

The enzyme, called reverse transcriptase (RT), copies RNA molecules and converts them into complementary DNA duplicates, which can then be inserted back into the DNA, creating permanent sequence changes in the cell's DNA blueprint.

HIV and many other viruses use RT to hijack a host's cells and cause chronic infection. Therefore, drugs that block the activity of the RT enzyme have become a common part of treatment cocktails to keep HIV at bay.

The brain appears to have its own RTs that are different from those in viruses, and the research team wondered whether inhibiting the brain's RTs with HIV drugs actually helps AD patients.

To assess the association between real-world RT inhibitor exposure and AD in humans, the team analyzed anonymized medical records containing prescription claims from more than 225,000 control and HIV-positive patients and found that RT inhibitor exposure was associated with a statistically significant reduced incidence and prevalence of AD.

Therefore, we studied HIV-positive individuals taking RT inhibitors and other combination antiretroviral therapies as they aged and asked the question: How many of them developed Alzheimer's disease? And the answer is that compared to the total population, there were far fewer than one could have expected.”

Jerold Chun, MD, Ph.D.

Of the more than 225,000 people with claims data in the study, nearly 80,000 were HIV-positive people over the age of 60. More than 46,000 had taken RT inhibitors during a nearly three-year observation period from 2016 to 2019. The data was obtained through a collaboration with health information technology and clinical research company IQVIA led by Tiffany Chow, MD

Among those living with HIV, there were 2.46 Alzheimer's diagnoses per 1,000 people among HIV-positive people taking these inhibitors, compared to 6.15 in the general population. This control group consisted of more than 150,000 HIV-negative patients over the age of 60 with health insurance claims related to treatment for a cold.

“You can’t do a prospective clinical trial with this number of patients,” Chun adds. “This approach is a way to study how a drug may affect a large patient population.”

Chun emphasizes that the drugs patients took in this retrospective study were designed to counteract RT activity in HIV and likely had only a limited effect on many different possible forms of the enzyme active in the brain.

“What we’re seeing now is very crude,” Chun says. "The clear next step for our lab is to identify which versions of RTs work in the AD brain so that more targeted treatments can be discovered. At the same time, prospective clinical trials of currently available RT inhibitors should be conducted in individuals with early-stage AD."

Jerold Chun, MD Ph.D., is a professor in the Center for Genetic Disorders and Aging Research at Sanford Burnham Prebys.

Other authors of the study are Tiffany W. Chow, Mark Raupp, Matthew W. Reynolds, Siying Li and Gwendolyn E. Kaeser.

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