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Repurposing Purine Analog Antivirals to Modulate Serum Uric Acid: Evidence From Real-World Data
Joseph Magagnoli1,2,3, Tammy H Cummings1,2,3, Michael D Wyatt4
1Department of Clinical Pharmacy and Outcomes Sciences, College of Pharmacy, University of South Carolina, Columbia, South Carolina, USA.
Clinical and Translational Science
|May 27, 2026
Summary
Cyclovir antivirals may lower serum uric acid levels by interacting with guanine deaminase, an enzyme in the purine degradation pathway. Real-world data suggest these drugs could be a novel approach for managing hyperuricemia.
Area of Science:
- Biochemistry
- Pharmacology
- Clinical Medicine
Background:
- Xanthine oxidase (XO) inhibitors are standard for hyperuricemia.
- Other enzymes in purine degradation, like guanine deaminase (GD), may also influence uric acid synthesis.
- Cyclovir antivirals are guanine nucleoside analogues that interact with GD.
Purpose of the Study:
- To investigate the association between cyclovir antiviral exposure and serum uric acid (sUA) levels.
- To explore the potential role of guanine deaminase in urate regulation.
Main Methods:
- Retrospective analysis of two independent real-world data sources: Merative MarketScan and US Veterans Health Administration.
- Comparison of patients exposed to cyclovir antivirals versus untreated controls with herpes simplex virus infection.
- Multivariable linear regression and inverse probability weighting to assess serum uric acid levels approximately one year after treatment initiation.
Main Results:
- Cyclovir antiviral exposure was associated with modest reductions in serum uric acid in both cohorts.
- In the MarketScan cohort, adjusted difference in sUA was -0.87 mg/dL (p=0.02) among patients with elevated baseline sUA.
- In the Veterans Health Administration cohort, adjusted difference in sUA was -0.87 mg/dL (p=0.003).
Conclusions:
- Cyclovir antiviral use is linked to reduced serum uric acid levels in real-world populations.
- These findings suggest a potential role for guanine deaminase in urate regulation.
- Further research is needed to confirm these effects and explore mechanistic pathways.
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