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J Infect Dis. 2003 Sep 15;188(6):883-90. Epub 2003 Sep 3.

Epstein-Barr virus replication in oral hairy leukoplakia: response, persistence, and resistance to treatment with valacyclovir.

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Department of Internal Medicine, Division of Infectious Diseases, University of Texas Medical Branch, Galveston 77555-0435, USA.


Nineteen cases of human immunodeficiency virus (HIV)-associated oral hairy leukoplakia (HLP) and Epstein-Barr virus (EBV) replication were treated with high-dose oral valacyclovir to inhibit productive EBV replication. The clinical, histopathological, and molecular viral responses to treatment were assessed in surgical biopsy specimens obtained before, during, and after treatment. In the majority of treated cases, HLP was resolved, and EBV replication was terminated. In many cases, the initial response to inhibition of replication was a persistent, nonproductive, EBV infection of the oral mucosa, characterized by limited expression of replicative EBV genes, especially BZLF1. In some cases, productive EBV replication recurred after discontinuation of treatment with valacyclovir. In a few treated cases, treatment failed, and productive EBV replication persisted, possibly because of the evolution of acyclovir-resistant EBV. In summary, safe treatment of HLP and of EBV replication, with valacyclovir, provides new insight into the mechanisms of EBV persistence in oral mucosa.

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