HIV Antiretroviral Reduced Alzheimer’s Risk Continuously, Study Shows

Patients taking nucleoside reverse transcriptase inhibitors (NRTIs) to treat their HIV have a decreased annual risk of developing Alzheimer’s disease by an average of 9% every year, according to research published today in Alzheimer’s and Dementia.

A team of researchers co-led by first authors Joseph Magagnoli, Ph.D., an assistant clinical pharmacy professor at the University of South Carolina and Meenakshi Ambati, a student at the Yale Jackson School of Global Affairs, used health insurance claims data from the United States Veterans Health Administration over a 24-year period and from the MarketScan database over a 14-year period. A total of 271,198 patients met the study criteria of being at least 50 years of age, diagnosed with HIV or hepatitis B (another disease treated with NRTIs) and with no prior Alzheimer’s disease diagnosis.

Patients in the VA sample had a 6% reduced hazard risk of Alzheimer’s for every additional year they spent taking an NRTI and patients in the MarketScan database had a 13% reduced hazard risk of Alzheimer’s every additional year, the study says.

“It’s estimated that over 10 million people around the world develop Alzheimer’s disease annually,” Jayakrishna Ambati, M.D., corresponding author and founding director of the University of Virginia School of Medicine’s Center for Advanced Vision Science, said in a news release. “Our results suggest that taking these drugs could prevent approximately 1 million new cases of Alzheimer’s disease every year.”

The team also found that exposure to other classes of HIV drugs, including protease inhibitors (PIs) or integrase strand transfer inhibitors (INSTIs), had no relation to Alzheimer’s risk reduction.

This discovery builds upon Ambati’s previous findings, which found that in addition to acting as an antiretroviral, NRTIs also prevent the activation of inflammasomes, a protein in cells that triggers inflammation in response to infections or cell damage. This latest research suggests that NRTIs address neuron inflammation, a leading theory on the cause of Alzheimer’s.

“These findings further buttress the concept that inflammasome inhibition by NRTIs in particular is protective against the development of AD rather than a generic result of anti-HIV therapy effect,” the authors write in the study.

Alzheimer’s disease is the leading cause of dementia worldwide. Approximately seven million Americans are living with the disease today, with an increase to 13 million expected by 2050. Annual costs of care for Alzheimer’s and other dementias could also reach $1 trillion by 2050, according to the Alzheimer’s Association. This includes 2.6- and 2.4-fold increases in government spending and out-of-pocket expenses.

“Our manuscript provides a rationale for testing the hypothesis that inflammasome inhibition could be beneficial for Alzheimer’s disease,” the authors write. “Examples of such testing could include (a) prospective, randomized clinical trials of NRTIs or less toxic derivatives and (b) mechanistic studies of such inflammasome inhibitors in animal models of Alzheimer’s disease.”