Detection of ganciclovir resistance after valacyclovir-prophylaxis in renal transplant recipients with active cytomegalovirus infection.
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.
Alain
S
S
Department of Bacteriology-Virology-Hygien, EA, Teaching Hospital Dupuytren, Limoges, France. sophie.alain@unilim.fr
Hantz
S
S
Scieux
C
C
Karras
A
A
Mazeron
M C
MC
Szelag
J C
JC
Imbert
B M
BM
Fillet
A M
AM
Gouarin
S
S
Mengelle
C
C
De Wilde
A
A
Cogne
N
N
Champier
G
G
Rogez
S
S
Legendre
C
C
Denis
F
F
D000212:Acyclovir / Q000031:analogs & derivatives* / Q000627:therapeutic use; D019943:Amino Acid Substitution; D000998:Antiviral Agents / Q000494:pharmacology* / Q000627:therapeutic use; D018890:Chemoprevention; D003587:Cytomegalovirus / Q000187:drug effects* / Q000235:genetics; D003586:Cytomegalovirus Infections / Q000188:drug therapy* / Q000821:virology; D024882:Drug Resistance, Viral / Q000235:genetics; D005260:Female; D015774:Ganciclovir / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D016030:Kidney Transplantation / Q000009:adverse effects*; D008875:Middle Aged; D010750:Phosphoproteins / Q000097:blood; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000235:genetics; D010865:Pilot Projects; D012189:Retrospective Studies; D000077483:Valacyclovir; D014633:Valine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D014763:Viral Matrix Proteins / Q000097:blood
D000998:Antiviral Agents; D010750:Phosphoproteins; D014763:Viral Matrix Proteins; C065418:cytomegalovirus matrix protein 65kDa; D017853:Phosphotransferases (Alcohol Group Acceptor); C075365:ganciclovir kinase; D014633:Valine; D000077483:Valacyclovir; D015774:Ganciclovir; D000212:Acyclovir