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

• Published in: Journal of medical virology Vol. 73; no. 4; pp. 566 - 573
• Main Authors: Alain, S., Hantz, S., Scieux, C., Karras, A., Mazeron, M.C., Szelag, J.C., Imbert, B.M., Fillet, A.M., Gouarin, S., Mengelle, C., de Wilde, A., Cogne, N., Champier, G., Rogez, S., Legendre, C., Denis, F.
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 01-08-2004; Wiley-Liss
• Subjects: Acyclovir - analogs & derivatives; Acyclovir - therapeutic use; Amino Acid Substitution; Antiviral Agents - pharmacology; Antiviral Agents - therapeutic use; Biological and medical sciences; Chemoprevention; Cytomegalovirus - drug effects; Cytomegalovirus - genetics; Cytomegalovirus Infections - drug therapy; Cytomegalovirus Infections - virology; Drug Resistance, Viral - genetics; Female; Fundamental and applied biological sciences. Psychology; Ganciclovir - pharmacology; Ganciclovir - therapeutic use; ganciclovir resistance; Human cytomegalovirus; Human viral diseases; Humans; Infectious diseases; Kidney Transplantation - adverse effects; Medical sciences; Microbiology; Middle Aged; Miscellaneous; Phosphoproteins - blood; Phosphotransferases (Alcohol Group Acceptor) - genetics; Pilot Projects; Retrospective Studies; valaciclovir transplantation; Valine - analogs & derivatives; Valine - therapeutic use; Viral diseases; Viral Matrix Proteins - blood; Virology; Human; ganciclovir resistance; Herpesviridae; Valaciclovir; Recipient; Transplantation; Homotransplantation; Betaherpesvirinae; Kidney; Human cytomegalovirus; Virus; Prevention; Resistance; Ganciclovir; Urinary system; Antiviral; Detection; valaciclovir transplantation
• ISSN: 0146-6615; 1096-9071
• DOI: 10.1002/jmv.20127

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. J. Med. Virol. 73:566–573, 2004. © 2004 Wiley‐Liss, Inc.