Long-term acyclovir for prevention of varicella zoster virus disease after allogeneic hematopoietic cell transplantation--a randomized double-blind placebo-controlled study.
Varicella-zoster virus (VZV) disease occurs in 30% of allogeneic hematopoietic cell transplant recipients who had a history of VZV infection. A safe and effective prevention strategy has not been established. In a double-blind controlled trial, 77 hematopoietic cell transplant recipients at risk for VZV reactivation were randomized to acyclovir 800 mg twice daily or placebo given from 1 to 2 months until 1 year after transplantation. VZV disease at 1 year was the primary end point; VZV disease after discontinuation of prophylaxis, VZV-specific T-cell immunity, herpes simplex virus (HSV) infection, cytomegalovirus (CMV) disease, survival, and safety were secondary end points. Acyclovir significantly reduced VZV infections at 1 year after transplantation (HR, 0.16; 95% CI, 0.035-0.74; P = .006). In the post-intervention observation period, this difference was not statistically significant (2 years: HR, 0.52; 95% CI, 0.21-1.3; 5 years: HR, 0.76; 95% CI, 0.36-1.6). There was no statistically significant difference in reconstitution of VZV-specific T-helper cell responses, HSV infections, CMV disease, chronic graft-versus-host disease, and overall survival between the groups. Acyclovir was well tolerated. Post-study VZV disease predominantly occurred in patients with continued need for systemic immunosuppression. In conclusion, acyclovir effectively and safely prevents VZV disease during the first year after hematopoietic cell transplantation. Periods of prophylaxis longer than 12 months may be beneficial for those hematopoietic cell transplant recipients on continued immune suppression.
Boeckh
Michael
M
Fred Hutchinson Cancer Research Center, Program in Infectious Diseases, 1100 Fairview Ave N, Seattle, WA 98109, USA. mboeckh@fhcrc.org
Kim
Hyung W
HW
Flowers
Mary E D
ME
Meyers
Joel D
JD
Bowden
Raleigh A
RA
D000212:Acyclovir / Q000008:administration & dosage*; D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D002908:Chronic Disease; D003587:Cytomegalovirus / Q000276:immunology; D003586:Cytomegalovirus Infections / Q000276:immunology / Q000517:prevention & control; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006086:Graft vs Host Disease / Q000209:etiology / Q000276:immunology / Q000821:virology; D019337:Hematologic Neoplasms / Q000150:complications / Q000276:immunology / Q000401:mortality / Q000628:therapy*; D018380:Hematopoietic Stem Cell Transplantation; D006561:Herpes Simplex / Q000276:immunology / Q000517:prevention & control; D006562:Herpes Zoster / Q000209:etiology / Q000276:immunology / Q000401:mortality / Q000517:prevention & control*; D006801:Humans; D008297:Male; D008875:Middle Aged; D018139:Simplexvirus / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology; D014184:Transplantation, Homologous; D014775:Virus Activation / Q000187:drug effects
D000212:Acyclovir