title: Incidence of cytomegalovirus UL97 and UL54 amino acid substitutions detected after 100 or 200 days of valganciclovir prophylaxis.
abstract: BACKGROUND
  The IMPACT study was a randomized, double-blind study comparing 100 to 200 days of VGCV prophylaxis (900 mg once daily) in D+/R- kidney transplant recipients. Although extending the duration of prophylaxis resulted in a significant reduction in confirmed cytomegalovirus (CMV) disease (100-day: 36.8% vs 200-day: 16.1%(1)), the consequence of extending the duration of prophylaxis on the development of viral resistance remains unknown.
  
  
  OBJECTIVE
  To determine whether extending valganciclovir prophylaxis from 100 days to 200 days increased the incidence of ganciclovir resistance.
  
  
  METHODS
  Genotypic analysis of CMV UL97 and UL54 was conducted on virus isolated from patients meeting the predefined resistance analysis criteria (RAC).
  
  
  RESULTS
  A greater number of patients met the RAC in the 100 day prophylaxis arm (50/163; 31%) compared to the 200 day prophylaxis arm (22/155; 14%). Sequence data were successfully generated for all 200-day patients and 48/50 100-day patients. Three patients in each treatment arm (100 day: 3/163 (1.8%) vs 200 day: 3/155 (1.9%)) had a single known valganciclovir resistance mutation detected (100 day: UL97 gene: M460V, C592G twice; 200 day: UL97 gene: C603W, M460V and UL54 gene: P522S). Overall, a resistance mutation was more likely to be detected if the patient met the RAC during prophylaxis (5/12 (42%)) compared to post-prophylaxis (1/58 (2%)). All six patients with known ganciclovir resistance mutations cleared the virus; three cleared virus without treatment and three cleared virus following treatment.
  
  
  CONCLUSIONS
  Extending valganciclovir prophylaxis from 100 days to 200 days did not significantly affect the incidence of ganciclovir resistance.
authors.affiliation: Centre Hospitalier Universitaire de Québec and Laval University, Québec, QC, Canada G1V 4G2.
authors.forename: Guy
authors.initials: G
authors.lastname: Boivin
authors.forename: Nathalie
authors.initials: N
authors.lastname: Goyette
authors.forename: Mahdi
authors.initials: M
authors.lastname: Farhan
authors.forename: Jane
authors.initials: J
authors.lastname: Ives
authors.forename: Robert
authors.initials: R
authors.lastname: Elston
mesh_terms: D019943:Amino Acid Substitution / Q000187:drug effects*; D019072:Antibiotic Prophylaxis; D000998:Antiviral Agents / Q000008:administration & dosage* / Q000009:adverse effects; D003587:Cytomegalovirus / Q000235:genetics* / Q000378:metabolism; D003586:Cytomegalovirus Infections / Q000097:blood / Q000517:prevention & control / Q000821:virology*; D004279:DNA, Viral / Q000097:blood; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D024882:Drug Resistance, Viral; D015774:Ganciclovir / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D006801:Humans; D016030:Kidney Transplantation / Q000379:methods*; D009154:Mutation; D000077562:Valganciclovir; D019562:Viral Load
chemical_list: D000998:Antiviral Agents; D004279:DNA, Viral; D000077562:Valganciclovir; D015774:Ganciclovir