Detection of ganciclovir resistance after valacyclovir-prophylaxis in renal transplant recipients with active cytomegalovirus infection

J Med Virol. 2004 Aug;73(4):566-73. doi: 10.1002/jmv.20127.

Abstract

Whether valaciclovir (VCV) prophylaxis could be responsible for ganciclovir (GCV)-resistance of Human cytomegalovirus (HCMV) in transplantation has never been documented. A multicentric retrospective pilot study was undertaken to detect GCV-resistance through mutations within the UL97 gene in renal transplant recipients who experienced active HCMV infection and received valacyclovir prophylaxis. Twenty-three patients who experienced HCMV antigenaemia or DNAemia during or at the end of prophylaxis were included. UL97 genotyping was carried out on peripheral blood samples, using a nested in-house PCR, which amplified the full-length UL97 gene. One patient has a resistance-related mutation (M460I); the major risk factor for emergence of resistance in this patient was the presence of early and persistent antigenaemia. GCV-resistance during VCV-prophylaxis was rare after renal transplantation. However, special attention must be paid to patients developing early active HCMV infection under prophylaxis.

Publication types

  • Case Reports
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acyclovir / analogs & derivatives*
  • Acyclovir / therapeutic use
  • Amino Acid Substitution
  • Antiviral Agents / pharmacology*
  • Antiviral Agents / therapeutic use
  • Chemoprevention
  • Cytomegalovirus / drug effects*
  • Cytomegalovirus / genetics
  • Cytomegalovirus Infections / drug therapy*
  • Cytomegalovirus Infections / virology
  • Drug Resistance, Viral / genetics
  • Female
  • Ganciclovir / pharmacology*
  • Ganciclovir / therapeutic use
  • Humans
  • Kidney Transplantation / adverse effects*
  • Middle Aged
  • Phosphoproteins / blood
  • Phosphotransferases (Alcohol Group Acceptor) / genetics
  • Pilot Projects
  • Retrospective Studies
  • Valacyclovir
  • Valine / analogs & derivatives*
  • Valine / therapeutic use
  • Viral Matrix Proteins / blood

Substances

  • Antiviral Agents
  • Phosphoproteins
  • Viral Matrix Proteins
  • cytomegalovirus matrix protein 65kDa
  • Phosphotransferases (Alcohol Group Acceptor)
  • ganciclovir kinase
  • Valine
  • Valacyclovir
  • Ganciclovir
  • Acyclovir