Topical treatment of infection with acyclovir-resistant mucocutaneous herpes simplex virus with the ribonucleotide reductase inhibitor 348U87 in combination with acyclovir.
The thiocarbonohydrazone 348U87 inactivates herpes simplex virus ribonucleotide reductase and potentiates the activity of acyclovir against wild-type and acyclovir-resistant strains of herpes simplex virus. We treated 10 human immunodeficiency virus-infected patients with acyclovir-resistant anogenital herpes simplex virus infection with a topical preparation of 348U87 (3%) in combination with acyclovir (5%) in an open-labelled study. Transient improvement with combination therapy occurred frequently; however, target lesions reepithelialized completely in only 1 of 10 patients. Termination of study drug therapy was most often due to cessation of therapeutic effect before complete resolution of lesions. As currently formulated, topical 348U87 offers little therapeutic benefit for this indication.
Department of Medicine, University of California, San Francisco.
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S
Safrin
T
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Schacker
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Delehanty
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E
Hill
L
L
Corey
D000212:Acyclovir / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D000287:Administration, Topical; D000998:Antiviral Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D004352:Drug Resistance, Microbial; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy; D006558:Herpes Genitalis / Q000150:complications / Q000188:drug therapy* / Q000382:microbiology; D006801:Humans; D006835:Hydrazones / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D011725:Pyridines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D012264:Ribonucleotide Reductases / Q000037:antagonists & inhibitors*; D018139:Simplexvirus / Q000187:drug effects*
D000998:Antiviral Agents; D006835:Hydrazones; D011725:Pyridines; C069703:compound 348U87; D012264:Ribonucleotide Reductases; D000212:Acyclovir