Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.1.21 (thymidine kinase)
 7,561 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Two patients with acquired immunodeficiency syndrome who developed severe ulcerative proctitis caused by herpes simplex virus type 2 that was resistant to acyclovir were successfully treated with 6 weeks of high-dose, continuous-infusion acyclovir sodium (1.5 to 2.0 mg/kg per hour). Viruses cultured from the lesions were resistant to acyclovir in vitro after the patients had received prolonged therapy with oral and intravenous acyclovir in traditional divided doses. Investigation into the mechanism of the acyclovir resistance revealed changes in the thymidine-kinase activity of both isolates. This viral enzyme phosphorylates acyclovir and is necessary for drug activation. The first patient's isolate was deficient of all thymidine-kinase activity, while the second patient's isolate had a thymidine kinase with altered substrate specificity for acyclovir. The continuous infusion was safe, well tolerated, and done in an outpatient setting with weekly clinic visits and monitoring of creatinine and acyclovir levels.
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PMID:Treatment of resistant herpes simplex virus with continuous-infusion acyclovir. 230 4

Human herpes simplex virus infections are very common and represent significant morbidity in the immunocompromised host. Patients with acyclovir resistant strains of HSV based on viral thymidine kinase gene mutations need alternative therapeutic approaches. Leflunomide has been shown to possess antiviral activity against several viruses. Herein we describe a case of acyclovir resistant HSV-2 proctitis in an HIV patient successfully treated with leflunomide without significant side effects.
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PMID:Successful treatment of acyclovir-resistant herpes simplex virus type 2 proctitis with leflunomide in an HIV-infected man. 2246 39