A Single Daily Ultra Low-Dose of Oral Acyclovir Is Sufficient to Prevent the Occurrence of Herpes Zoster Post Hematopoietic Stem Cell Transplantation: Interim Results of a Prospective Randomized Trial

Prophylactic acyclovir has been shown to decrease the risk of varicella zoster virus (VZV) reactivation following hematopoietic stem transplantation (HSCT). In order to improve compliance and to minimize potential toxicity, we investigated the role of a single daily ultra low-dose of acyclovir in preventing the occurrence of herpes zoster (HZ) following HSCT. Between June 2008 till date, all HSCT patients in this center are being randomized after informed consent, to either receive low-dose acyclovir (LD Group) at 800mg twice daily (20mg/kg twice daily if <40kg) or ultra low-dose acyclovir (uLD Group) at 200mg once daily (5mg/kg/day if <40kg) for one year following HSCT. The primary endpoint of this study is the occurrence of HZ at one year. For this interim per-protocol analysis, a total of 80 consecutive patients with a minimum of 6 months of follow up following cessation of therapy were eligible for analysis. There were 40 patients in each group. Both groups were comparable for age, median 11 yrs (0.3-53) in the LD group vs 13 yrs (0.5-43) in the uLD group, underlying disease, type of transplant, graft versus host disease and median time of randomization (33.4 vs 38 days post HSCT). None of the patients in the uLD group developed HZ while on prophylaxis. One patient in the LD group developed HZ (2.5%). This patient had a past history of recurrent herpes zoster in the same dermatomal distribution prior to HSCT while on therapy for acute leukemia. Five patients developed HZ within 5 months after discontinuing acyclovir (LD group = 1, uLD group = 4, p=0.358). Amongst these patients the median time to develop HZ after stopping prophylaxis was 31 days (9-142 days). This prospective randomized study shows that a single daily ultra low-dose of acyclovir given for one year following HSCT is sufficient to prevent HZ during a time when the patient is most vulnerable to the consequences of VZV reactivation. Prolongation of prophylaxis beyond a year may be necessary for patients who continue to be severely immunosuppressed.