title: Cytomegalovirus disease and infection in lung transplant recipients in the setting of planned indefinite valganciclovir prophylaxis.
abstract: BACKGROUND
  The optimal method of both predicting and preventing cytomegalovirus (CMV) disease in lung transplant recipients remains unclear. In particular, the most appropriate duration of CMV prophylaxis post transplant is unresolved. We report herein our experience with a planned indefinite regimen of valganciclovir prophylaxis and monitoring of quantitative CMV load in bronchoalveolar lavage (BAL) fluid.
  
  
  METHODS
  We performed a single-center observational study with both prospective and retrospective components. The included patients (n = 128) received a planned regimen of indefinite valganciclovir prophylaxis post transplant, regardless of donor (D)/recipient (R) CMV serostatus. Real-time polymerase chain reaction assay for detection of CMV in BAL was prospectively performed over a 1-year period. Clinical data were reviewed retrospectively; median follow-up was 24.8 months (range 1-93 months).
  
  
  RESULTS
  Sixty-five patients (50.6%) discontinued valganciclovir prophylaxis, either temporarily or permanently, with a primary cause of mild leukopenia. Six cases of CMV disease were identified (4.7%), with no significant difference between those who were on continuous prophylaxis or not (4.6% vs. 4.9%; P = non-significant [ns]). However, those who discontinued prophylaxis showed an increased incidence of laboratory-detected CMV infection (40.7% vs. 12.7%; P = 0.001). High-risk D+/R- patients did not demonstrate a significantly increased incidence of CMV disease (8.1% vs. 3.3% other serotypes; P = ns). Three patients (2.3%) developed valganciclovir-resistant CMV disease. Molecular detection of CMV in BAL fluid was significantly more sensitive than shell vial culture. However, BAL CMV viral load was not predictive of subsequent disease development.
  
  
  CONCLUSIONS
  Extended valganciclovir prophylaxis for all lung transplant recipients led to a low incidence of CMV disease and resistance. In such low-incidence populations, routine quantitation of CMV in BAL did not confer significant clinical benefit over non-quantitative methods in prediction of CMV disease onset.
authors.affiliation: Department of Laboratory Medicine, University of California, San Francisco, California 94107, USA.
authors.forename: A P
authors.initials: AP
authors.lastname: Wiita
authors.forename: N
authors.initials: N
authors.lastname: Roubinian
authors.forename: Y
authors.initials: Y
authors.lastname: Khan
authors.forename: P V
authors.initials: PV
authors.lastname: Chin-Hong
authors.forename: J P
authors.initials: JP
authors.lastname: Singer
authors.forename: J A
authors.initials: JA
authors.lastname: Golden
authors.forename: S
authors.initials: S
authors.lastname: Miller
mesh_terms: D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000627:therapeutic use*; D001992:Bronchoalveolar Lavage Fluid / Q000821:virology; D003587:Cytomegalovirus / Q000235:genetics / Q000302:isolation & purification*; D003586:Cytomegalovirus Infections / Q000453:epidemiology / Q000517:prevention & control* / Q000821:virology; D004279:DNA, Viral / Q000032:analysis; D005260:Female; D015774:Ganciclovir / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006801:Humans; D016040:Lung Transplantation; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D060888:Real-Time Polymerase Chain Reaction; D012189:Retrospective Studies; D000077562:Valganciclovir; D019562:Viral Load
chemical_list: D000998:Antiviral Agents; D004279:DNA, Viral; D000077562:Valganciclovir; D015774:Ganciclovir