title: Evaluation of Low- Versus High-dose Valganciclovir for Prevention of Cytomegalovirus Disease in High-risk Renal Transplant Recipients.
abstract: BACKGROUND
  Despite proven efficacy of prolonged cytomegalovirus (CMV) prophylaxis using valganciclovir 900 mg/day, some centers use 450 mg/day due to reported success and cost savings. This multicenter, retrospective study compared the efficacy and safety of 6 months of low-dose versus high-dose valganciclovir prophylaxis in high-risk, donor-positive/recipient-negative, renal transplant recipients (RTR).
  
  
  METHODS
  Two hundred thirty-seven high-risk RTR (low-dose group = valganciclovir 450 mg/day [n = 130]; high-dose group = valganciclovir 900 mg/day [n = s7]) were evaluated for 1-year CMV disease prevalence. Breakthrough CMV, resistant CMV, biopsy-proven acute rejection (BPAR), graft loss, opportunistic infections (OI), new-onset diabetes after transplantation (NODAT), premature valganciclovir discontinuation, renal function and myelosuppression were also assessed.
  
  
  RESULTS
  Patient demographics and transplant characteristics were comparable. Induction and maintenance immunosuppression were similar, except for more early steroid withdrawal in the high-dose group. Similar proportions of patients developed CMV disease (14.6% vs 24.3%; P = 0.068); however, controlling CMV risk factor differences through multivariate logistic regression revealed significantly lower CMV disease in the low-dose group (P = 0.02; odds ratio, 0.432, 95% confidence interval, 0.211-0.887). Breakthrough and resistant CMV occurred at similar frequencies. There was no difference in renal function or rates of biopsy-proven acute rejection, graft loss, opportunistic infections, or new-onset diabetes after transplantation. The high-dose group had significantly lower mean white blood cell counts at months 5 and 6; however, premature valganciclovir discontinuation rates were similar.
  
  
  CONCLUSIONS
  Low-dose and high-dose valganciclovir regimens provide similar efficacy in preventing CMV disease in high-risk RTR, with a reduced incidence of leukopenia associated with the low-dose regimen and no difference in resistant CMV. Low-dose valganciclovir may provide a significant cost avoidance benefit.
authors: 1 Departments of Transplant Surgery and Pharmacy Services, and the Renal Division, Brigham and Women's Hospital, Boston, MA. 2 Harvard Medical School, Boston, MA. 3 Department of Pharmacy Services, Beth Israel Deaconess Medical Center, Boston, MA. 4 Department of Pharmacy Services, Henry Ford Hospital, Detroit, MI. 5 Department of Pharmacy Services, University of California San Diego Medical Center, San Diego, CA. 6 Department of Transplant Surgery and Pharmacy Services, Tufts Medical Center, Boston, MA. 7 Department of Pharmacy Services, Brigham and Women's Hospital, Boston, MA. 8 Department of Pharmacy Services, Yale New Haven Hospital, New Haven, CT. 9 Department of Pharmacy Services, University of California Irvine Medical Center, Orange, CA. 10 Department of Pharmacy Services, Massachusetts General Hospital, Boston, MA.
authors: Steven
authors: S
authors: Gabardi
authors: Natalya
authors: N
authors: Asipenko
authors: James
authors: J
authors: Fleming
authors: Kevin
authors: K
authors: Lor
authors: Lisa
authors: L
authors: McDevitt-Potter
authors: Anisa
authors: A
authors: Mohammed
authors: Christin
authors: C
authors: Rogers
authors: Eric M
authors: EM
authors: Tichy
authors: Renee
authors: R
authors: Weng
authors: Ruth-Ann
authors: RA
authors: Lee
mesh_terms: D000208:Acute Disease; D000328:Adult; D000998:Antiviral Agents / Q000008:administration & dosage* / Q000009:adverse effects; D003586:Cytomegalovirus Infections / Q000175:diagnosis / Q000453:epidemiology / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D005260:Female; D015774:Ganciclovir / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D006084:Graft Rejection / Q000276:immunology / Q000517:prevention & control; D006085:Graft Survival / Q000187:drug effects; D006801:Humans; D016867:Immunocompromised Host; D053208:Kaplan-Meier Estimate; D016030:Kidney Transplantation / Q000009:adverse effects*; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D016017:Odds Ratio; D009894:Opportunistic Infections / Q000175:diagnosis / Q000453:epidemiology / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D015995:Prevalence; D012189:Retrospective Studies; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome; D014481:United States / Q000453:epidemiology; D000077562:Valganciclovir
chemical_list: D000998:Antiviral Agents; D000077562:Valganciclovir; D015774:Ganciclovir