title: Resistance pattern of cytomegalovirus (CMV) after oral valganciclovir therapy in transplant recipients at high-risk for CMV infection.
abstract: In transplant recipients, cytomegalovirus (CMV) resistance to antivirals causes an increasing problem. Here we report the clinical, therapeutic, and virological characteristics of 11 cases of CMV resistance among transplant recipients at high-risk for CMV infection and receiving valganciclovir as a prophylactic, preemptive or maintenance therapy. Active CMV infection was monitored by viral DNA quantification in whole blood, and CMV resistance was assessed by UL97 and UL54 viral gene sequencing. For 10 patients, ganciclovir resistance detected after valganciclovir therapy was associated with one mutation within UL97 phosphotransferase located at codons 460 and 592-603, which constitutes a similar pattern of resistance to what has been reported previously in AIDS patients treated with valganciclovir. For the last patient, two mutations in UL97 and UL54 genes were identified. The start of valganciclovir maintenance treatment after an intravenous curative treatment while CMV DNA is still detectable in peripheral blood might represent a risk factor for the emergence of CMV resistance. The possible emergence of CMV resistance in transplant recipients at high-risk for CMV infection who receive valganciclovir therapy should be taken into account. Among those patients, CMV infection has to be closely monitored in order to detect promptly the emergence of drug-resistance.
authors.affiliation: UPMC Univ Paris 06, UPRES EA 2387, F-75013 Paris, France. david.boutolleau@psl.aphp.fr
authors.forename: David
authors.initials: D
authors.lastname: Boutolleau
authors.forename: Claire
authors.initials: C
authors.lastname: Deback
authors.forename: Céline
authors.initials: C
authors.lastname: Bressollette-Bodin
authors.forename: Shaida
authors.initials: S
authors.lastname: Varnous
authors.forename: Nathalie
authors.initials: N
authors.lastname: Dhedin
authors.forename: Benoît
authors.initials: B
authors.lastname: Barrou
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Vernant
authors.forename: Iradj
authors.initials: I
authors.lastname: Gandjbakhch
authors.forename: Berthe-Marie
authors.initials: BM
authors.lastname: Imbert-Marcille
authors.forename: Henri
authors.initials: H
authors.lastname: Agut
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001769:Blood / Q000821:virology; D018890:Chemoprevention; D003587:Cytomegalovirus / Q000187:drug effects*; D003586:Cytomegalovirus Infections / Q000517:prevention & control*; D004279:DNA, Viral / Q000097:blood; D024882:Drug Resistance, Viral; D005260:Female; D015774:Ganciclovir / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D014180:Transplantation; D000077562:Valganciclovir; D019562:Viral Load; D014764:Viral Proteins / Q000235:genetics
chemical_list: D000998:Antiviral Agents; D004279:DNA, Viral; D014764:Viral Proteins; D000077562:Valganciclovir; D015774:Ganciclovir