title: Long-term efficacy and safety of 12 months of valganciclovir prophylaxis compared with 3 months after lung transplantation: a single-center, long-term follow-up analysis from a randomized, controlled cytomegalovirus prevention trial.
abstract: BACKGROUND
  The optimal approach to cytomegalovirus (CMV) prevention after lung transplantation is controversial. We recently completed a prospective, randomized, placebo-controlled study of CMV prevention in lung transplantation that demonstrated the short-term efficacy and safety of extending valganciclovir prophylaxis to 12 months vs 3 months of therapy. In the current analysis, we monitored a single-center subset of patients enrolled in the CMV prevention trial to determine if extended prophylaxis conferred a sustained long-term benefit and to assess its hematologic safety.
  
  
  METHODS
  The sub-analysis included 38 randomized patients from Duke University Medical Center. All patients underwent consistent serial serum CMV monitoring and surveillance bronchoscopies. CMV was defined by viremia (≥ 500 CMV DNA copies/ml) or pneumonitis. The safety assessment included a review of all complete blood counts obtained from transplant onward.
  
  
  RESULTS
  During a mean follow-up of 3.9 years in each group, extended-course compared with short-course prophylaxis provided a sustained protective benefit with a lifetime CMV incidence of 12% vs 55%, respectively (hazard ratio, 0.13; 95% confidence interval, 0.03-0.61; p = 0.009), an effect that persisted after adjustment for clinical risk factors. Patients in each group underwent a comparable number of peripheral blood draws and bronchoscopies. Post-transplant white blood cell, neutrophil, and platelet counts were similar between each treatment group during the course of follow-up.
  
  
  CONCLUSIONS
  Extending valganciclovir prophylaxis to 12 months provides a durable long-term CMV protective benefit compared with short-course therapy, without increasing adverse hematologic effects.
authors.affiliation: Department of Medicine, Duke University Medical Center, Durham, North Carolina 27710, USA.
authors.forename: C Ashley
authors.initials: CA
authors.lastname: Finlen Copeland
authors.forename: W Austin
authors.initials: WA
authors.lastname: Davis
authors.forename: Laurie D
authors.initials: LD
authors.lastname: Snyder
authors.forename: Missy
authors.initials: M
authors.lastname: Banks
authors.forename: Robin
authors.initials: R
authors.lastname: Avery
authors.forename: R Duane
authors.initials: RD
authors.lastname: Davis
authors.forename: Scott M
authors.initials: SM
authors.lastname: Palmer
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001999:Bronchoscopy; D003550:Cystic Fibrosis / Q000601:surgery; D003587:Cytomegalovirus / Q000302:isolation & purification; D003586:Cytomegalovirus Infections / Q000517:prevention & control*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005500:Follow-Up Studies; D015774:Ganciclovir / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006801:Humans; D008137:Longitudinal Studies; D008168:Lung / Q000821:virology; D008171:Lung Diseases / Q000175:diagnosis / Q000517:prevention & control* / Q000821:virology*; D016040:Lung Transplantation; D008297:Male; D008875:Middle Aged; D029424:Pulmonary Disease, Chronic Obstructive / Q000601:surgery; D011658:Pulmonary Fibrosis / Q000601:surgery; D013997:Time Factors; D016896:Treatment Outcome; D000077562:Valganciclovir
chemical_list: D000998:Antiviral Agents; D000077562:Valganciclovir; D015774:Ganciclovir