title: Analysis of HHV-6 mutations in solid organ transplant recipients at the onset of cytomegalovirus disease and following treatment with intravenous ganciclovir or oral valganciclovir.
abstract: BACKGROUND
  Human herpesvirus 6 (HHV-6) and human cytomegalovirus (HCMV) are major opportunistic pathogens in solid organ transplant (SOT) recipients. The use of antivirals for the treatment of HCMV disease can result in the development of drug resistance mutations in HCMV and also potentially in HHV-6.
  
  
  OBJECTIVE
  The emergence of HHV-6 drug resistance mutations was evaluated in SOT recipients at the onset of HCMV disease and following treatment with ganciclovir (GCV) or valganciclovir (VGCV).
  
  
  METHODS
  Detection of HHV-6 was performed by real-time PCR from whole blood samples serially obtained from SOT recipients treated for HCMV disease with an induction dose of intravenous GCV or oral VGCV for 21 days followed by VGCV maintenance for 28 days in both arms. Baseline and last positive HHV-6 samples were tested for mutations in the genes encoding the protein kinase (U69) and the DNA polymerase (U38).
  
  
  RESULTS
  The rate of HHV-6 viraemia among SOT patients with HCMV disease at baseline was 3.2% (5/155). All isolates belonged to the HHV-6B species. Mutations L213I and Y479H were detected at baseline and at later times in the U69 kinase. Mutation L213I was previously reported as polymorphism whereas the role of mutation Y479H in drug resistance is unknown. Mutations D854E and E855Q found in the DNA polymerase were known as natural variants.
  
  
  CONCLUSIONS
  The incidence of HHV-6 viraemia in SOT recipients with established HCMV disease before initiation of antiviral therapy was low. Treatment with GCV or VGCV did not induce the emergence of HHV-6 drug resistance mutations.
authors.affiliation: Infectious Diseases Research Center of the CHU of Québec, and Laval University, Quebec City, Quebec, Canada G1V 4G2.
authors.forename: Lotfi
authors.initials: L
authors.lastname: Bounaadja
authors.forename: Jocelyne
authors.initials: J
authors.lastname: Piret
authors.forename: Nathalie
authors.initials: N
authors.lastname: Goyette
authors.forename: Guy
authors.initials: G
authors.lastname: Boivin
mesh_terms: D000998:Antiviral Agents / Q000627:therapeutic use*; D060085:Coinfection / Q000821:virology; D003586:Cytomegalovirus Infections / Q000188:drug therapy*; D004279:DNA, Viral / Q000737:chemistry / Q000235:genetics; D024882:Drug Resistance, Viral; D015774:Ganciclovir / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D015654:Herpesvirus 6, Human / Q000235:genetics* / Q000302:isolation & purification; D006801:Humans; D020125:Mutation, Missense; D060888:Real-Time Polymerase Chain Reaction; D019349:Roseolovirus Infections / Q000821:virology*; D017422:Sequence Analysis, DNA; D014180:Transplantation; D019737:Transplants; D000077562:Valganciclovir; D014764:Viral Proteins / Q000235:genetics
chemical_list: D000998:Antiviral Agents; D004279:DNA, Viral; D014764:Viral Proteins; D000077562:Valganciclovir; D015774:Ganciclovir
keywords: Antivirals; Co-infections; Drug resistance mutations; GCV; HCMV; HHV-6; ND; NT; SOT; VGCV; ganciclovir; human cytomegalovirus; human herpesvirus 6; not determined; not tested; solid organ transplant; valganciclovir