1463. Association between Herpes Simplex Virus Type 1 and the Risk of Alzheimer’s Disease

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Abstract Background There is significant unmet need of novel therapeutics for Alzheimer’s Disease (AD). A growing body of evidence suggests a role for herpesviruses in the development of AD and reduced risk of AD among patients receiving antivirals. We investigated the association between herpes simplex virus type 1 (HSV-1) diagnoses, antiviral use, and AD using real-world data. Methods In a matched case-control study, AD patients aged ≥ 50 years diagnosed between 2006 and 2021 were identified from IQVIA PharMetrics Plus® claims database using International Classification of Disease (ICD) codes (ICD 9 331.0; ICD 10 G30.x). Controls without any history of neurological disorders were matched in a 1:1 ratio with AD subjects on age, sex, region, database entry year, and healthcare visit numbers. HSV-1 diagnoses were identified using relevant ICD codes. Conditional logistic regression was used to evaluate the association between HSV-1 and AD. The association between antiviral use (e.g., acyclovir, famciclovir, valacyclovir) and AD was assessed by multivariate Cox proportional hazards model in patients with HSV-1 diagnosis. Results The study included 344,628 AD patient-control pairs. Most patients were female (65%) with a mean age of 73 (± 5) years. AD patients had more comorbidities (50% vs. 45% with ≥ 2 comorbidities) and shorter follow up time (median of 33 vs. 48 months) when compared to controls. History of HSV-1 diagnosis was present in 1507 (0.44%) AD patients vs. 823 (0.24%) controls. HSV-1 diagnosis was associated with AD (adjusted odds ratio [OR] 1.80; 95% confidence interval [CI] 1.65-1.96). In a stratified analysis, this association was more pronounced in the older age group (75+ years: OR 2.10, 95% CI 1.88-2.35; 71-74 years: OR 1.51, 95% CI 1.27-1.80; 50-70 years: OR 1.14, 95% CI 0.91-1.44). Patients with HSV-1 who used antivirals were less likely to have AD compared to those who did not use antivirals (adjusted hazard ratio 0.83, 95% CI 0.74-0.92). Similar results were observed when the analysis was extended to include all patients with AD-related dementia and matched controls. The association between herpes simplex virus type 1 (HSV-1) and Alzheimer’s Disease (AD)/AD-related Dementia(ADRD) Conclusion Findings from this large real-world data study is consistent with emerging literature on HSV-1 and risk of AD and the possible protective role of antiviral drugs. Disclosures Luke Liu, PhD, Gilead Sciences, Inc.: Employee|Gilead Sciences, Inc.: Stocks/Bonds Christine Johnston, MD, MPH, AbbVie: Advisor/Consultant|Gilead: Grant/Research Support|GSK: Advisor/Consultant Simon P. Fletcher, PhD, Gilead Sciences, Inc.: Employee|Gilead Sciences, Inc.: Stocks/Bonds Shahed Iqbal, PhD, MBBS, Gilead Sciences, Inc.: Employee|Gilead Sciences, Inc.: Stocks/Bonds.