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TOPLINE:

Use of nucleoside reverse transcriptase inhibitors (NRTIs), but not other medications for HIV, was associated with a significantly reduced risk for Alzheimer’s disease (AD) in an analysis of two national databases. NRTIs are antiretroviral drugs that block the activation of inflammasome.

METHODOLOGY:

• This study included data of nearly 272,000 US individuals from two national databases: The Veterans Health Administration (VA) database (2000-2024; n = 72,193) and the MarketScan database (2006-2020; n = 199,005).
• Researchers evaluated patients aged 50 years or older with a medical claim for HIV/AIDS or hepatitis B during the study period. Use of NRTIs was calculated using prescription days’ supply.
• The primary outcome was incident AD.
• The analysis involved propensity score matching, and confounders included age, sex, race, and comorbidities.

TAKEAWAY:

• After adjusting for confounders, each additional year of NRTI exposure was associated with a 6% reduced hazard for AD in the VA cohort (adjusted hazard ratio [aHR], 0.94; 95% CI, 0.89-0.999) and a 13% reduced hazard in the MarketScan cohort (aHR, 0.87; 95% CI, 0.779-0.972).
• After also adjusting for the competing risk for mortality, the use of NRTIs was linked to a reduced risk for AD in the VA cohort only (aHR, 0.63; 95% CI, 0.46-0.85).
• Additionally, NRTIs were associated with a reduced risk for incident AD in HIV-positive and hepatitis B–positive patients (P < .05 for both).
• Other antiretroviral medications were not associated with lower AD risk.

IN PRACTICE:

“These findings support the concept that inflammasome inhibition could benefit AD and provide a rationale for prospective clinical testing of inflammasome inhibitors such as NRTIs in AD,” the investigators wrote.

“Our results suggest that taking these drugs could prevent approximately 1 million new cases of AD every year,” corresponding investigator Jayakrishna Ambati, MD, Center for Advanced Vision Science, University of Virginia School of Medicine, Charlottesville, Virginia, said in a press release.

SOURCE:

This study was led by Joseph Magagnoli, Dorn Research Institute, Columbia VA Health Care System, Columbia, South Carolina. It was published online on May 08 in Alzheimer’s and Dementia.

LIMITATIONS:

This study was limited by potential residual or unmeasured confounding, lack of genetic data, lack of clinical measures of disease progression, and potential biases from differences among cohorts in terms of healthcare access and diagnostic practices.

DISCLOSURES:

This study was supported by the University of Virginia Strategic Investment Fund Grant and National Institutes of Health grants, the DuPont Guerry III Professorship, and a gift from Mr and Mrs Eli W. Tullis. Several investigators reported having various ties with various organizations. Full details are provided in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.