Alzheimer’s disease (AD) is a significant medical issue in the United States, affecting nearly seven million people with projections estimating this number to reach nearly 13 million by 2050. The lack of effective therapies for AD represents a major unmet medical need. A study led by Jerold Chun, M.D., Ph.D., at Sanford Burnham Prebys has identified potential connections between common HIV drugs and a reduced incidence of AD. The research builds on previous work that revealed how somatic gene recombination in neurons can produce new gene variants within AD brains, with the same enzyme found in HIV playing a role in the process.
Reverse transcriptase (RT) is the enzyme central to the study, which copies RNA molecules and converts them into complementary DNA duplicates that can be inserted back into DNA, leading to permanent changes within the cell’s DNA blueprint. Many viruses, including HIV, rely on RT to infect cells and establish a chronic infection. Consequently, drugs that inhibit the RT enzyme are commonly used as part of treatment regimens for HIV to prevent viral replication. The study aimed to determine if inhibiting brain RTs with HIV drugs could potentially benefit AD patients by analyzing real-world links between RT inhibitor exposure and AD incidence and prevalence in humans.
Over 225,000 control and HIV-positive patients’ anonymized medical records were analyzed, showing that RT inhibitor exposure was associated with a statistically significant reduction in the incidence and prevalence of AD. Fewer cases of AD were observed in HIV-positive individuals taking RT inhibitors compared to the general population. The data, obtained in collaboration with IQVIA, led by Tiffany Chow, M.D., revealed promising outcomes in terms of AD incidence in patients taking RT inhibitors during the observation period from 2016 to 2019. While the findings are significant, further research is required to identify the specific types of RTs at work in the AD brain for more targeted treatments.
In living persons with HIV, the study showed a lower incidence of AD diagnoses per 1,000 individuals among those taking RT inhibitors compared to the general population. This retrospective study provides valuable insights into how these inhibitors could impact a large patient population and potentially benefit individuals with AD. Jerold Chun emphasizes the need for further research to identify specific versions of RTs in the AD brain to develop more targeted treatments. Prospective clinical trials with currently available RT inhibitors on individuals with early AD should also be explored to validate the study’s findings.
Jerold Chun, M.D., Ph.D., is a professor at the Center for Genetic Disorders and Aging Research at Sanford Burnham Prebys and led the study on the potential links between HIV drugs and reduced AD incidence. Other authors involved in the research include Tiffany W. Chow, Mark Raupp, Matthew W. Reynolds, Siying Li, and Gwendolyn E. Kaeser. Funding for the study was provided by the National Institute on Aging — NIH, the Shaffer Family Foundation, and the Bruce Ford & Anne Smith Bundy Foundation. The study represents a significant step towards understanding the potential benefits of RT inhibitors in reducing the incidence and prevalence of AD, highlighting the importance of further research in developing targeted treatments.
