Low-Dose Acyclovir Recommended for HSV Prophylaxis in Leukemic Patients

SAN FRANCISCO-Low-dose intravenous acyclovir (Zovirax) provideseffective prophylaxis against Herpes simplex virus (HSV)infection or reactivation in leukemic patients undergoing intensivechemotherapy, Carole Miller, MD, said at the 35th InterscienceConference on Antimicrobial Agents and Chemotherapy (ICAAC).

Furthermore, using IV acyclovir at dosages as low as 62.5 mg/m²every 4 hours results in a 50% decrease in drug cost over standarddosing, and the technique of administration does not increasenursing time, said Dr. Miller, assistant professor of oncology,Johns Hopkins University.

Until the advent of acyclovir, HSV infections were a significantcause of morbidity in patients undergoing intensive high-dosechemotherapy for leukemia, Dr. Miller pointed out.

About a decade ago, the effect of acyclovir as a prophylacticagent against reactivation of HSV was assessed at Johns Hopkinsin a randomized, double-blind, placebo-controlled study. In thisearlier trial, 73% of the placebo group developed culture-positiveHSV infection from a mucocutaneous lesion, while none in the prophylaxedgroup became positive.

To determine a minimal effective dose and schedule of acyclovirfor preventing HSV infection or reactivation, three studies wereset up, Dr. Miller said.

Overall, 517 persons with leukemia (AML-76%, ALL-16%, CML-8%)undergoing intensive chemotherapy received 1,000 courses of prophylacticacy-clovir with three consecutive regimens: 250 mg/m² q8hfor 309 courses; 125 mg/m² q6h for 225 courses; and 62.5mg/m² q4h for 466 courses. The median duration of prophylaxiswas 36.9 days (the median duration of bone marrow aplasia).

Patients were evaluable if they received a minimum of 7 days ofacyclovir prophylaxis, as well as having all negative surveillancecultures (throat, urine, blood) pre-acyclovir and within the first72 hours of beginning prophylaxis.

Only Two Failures

Skin and oral exams were carried out daily, and oral viral culturesfor HSV were done every week or if clinically indicated. A failurewas defined as a positive culture with or without lesions. Orallesions without a positive culture were not considered failures,as oral mucositis is common with intensive chemotherapy.

Of the 1,000 courses of acyclovir prophylaxis, Dr. Miller said,998 had no evidence of HSV infection or reactivation. Only twofailures were seen, both occurring in the 250 mg/m² every8 hours arm.

Dr. Miller said that 99 of 1,000 courses of acyclovir requireddose reduction for renal insufficiency. Also, in 28 of 1,000 courses,the dose of acyclovir was increased due to severe mucositis. Interestingly,this was done at the doctors' request and was not, in any of thecases, related to viral culture.