Frequency and Significance of Acyclovir-Resistant Herpes Simplex Virus Isolated from Marrow Transplant Patients Receiving Multiple Courses of Treatment with Acyclovir

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Abstract
The sensitivity to acyclovir of virus isolates from 52 consecutive marrow transplant patients who received acyclovir for herpes simplex virus infections was studied in vitro. The median sensitivity of viruses obtained during first, second, third, and fourth recurrences was similar, and the median duration of virus positivity (three days) was the same for first and second treatment courses. However, acyclovir-resistant virus was recovered from one of 52 patients (1.9%) during the initial treatment course and from two of 22 patients (9.1%) treated for second recurrences. All three strains had reduced thymidine kinase activity. None caused severe infection. Three other patients remained virus-positive during treatment despite the isolation of acyclovir-sensitive virus. Although continuing surveillance is necessary, these data may suggest that acyclovir-resistant virus will not be the cause of significant clinical illness among immunosuppressed patients. In addition, not all instances of “resistance,” defined by the persistence of virus during treatment, will be caused by virus strains that are resistant to acyclovir in vitro.