Emerging research suggests that certain HIV drugs might have potential in preventing or treating Alzheimer’s disease (AD), but the evidence is still preliminary. Here’s what we know so far:

1. Antiretroviral Drugs (ARVs) and Alzheimer’s Risk

• Epidemiological Observations: Some studies have found that people living with HIV on long-term antiretroviral therapy (ART) show a lower incidence of Alzheimer’s disease compared to the general population.
• Possible Mechanisms:
  • Reduction of Neuroinflammation: HIV drugs, particularly protease inhibitors (e.g., ritonavir, lopinavir), may suppress chronic inflammation, a key factor in Alzheimer’s.
  • Blocking Viral-Like Mechanisms: Some theories suggest Alzheimer’s could involve virus-like activity (e.g., herpesviruses, endogenous retroviruses), which ARVs might inhibit.
  • Amyloid & Tau Modulation: Certain HIV drugs may interfere with amyloid-beta (Aβ) aggregation or tau phosphorylation.

2. Specific Drugs Under Investigation

• Nelfinavir (Protease Inhibitor):
  • A 2019 Nature Communications study found it enhanced lysosomal clearance of Aβ and tau in cell and mouse models.
• Lamivudine (NRTI):
  • Research suggests it may reduce age-related inflammation by blocking endogenous retroelements.
• Efavirenz (NNRTI):
  • Shown in some studies to promote Aβ clearance, but concerns about neuropsychiatric side effects exist.

3. Challenges & Caveats

• Not All HIV Drugs May Work: Some ARVs could even worsen neurodegeneration (e.g., older NRTIs like stavudine).
• Lack of Clinical Trials: Most evidence comes from animal or cell studies—no large-scale human trials yet.
• Side Effects: Long-term use of HIV drugs can have liver, metabolic, or neurological side effects in non-HIV patients.

4. Future Directions

• Repurposing Trials: Researchers are exploring whether low-dose ARVs could benefit Alzheimer’s patients.
• Focus on Neuroinflammation: If viral elements contribute to AD, ARVs might be part of a combination therapy.

Reference:

https://www.sciencealert.com/hiv-drugs-dramatically-lower-risk-of-alzheimers-disease-study-finds

https://www.aidsmap.com/news/may-2024/class-hiv-drugs-might-protect-against-alzheimers

https://www.insideprecisionmedicine.com/topics/translational-research/hiv-drugs-linked-to-lower-alzheimers-risk/

https://www.medicalnewstoday.com/articles/hiv-drugs-help-prevent-alzheimers-disease-nrti

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