title: High incidence of anticytomegalovirus drug resistance among D+R- kidney transplant recipients receiving preemptive therapy.
abstract: Anti-cytomegalovirus (CMV) prophylaxis is recommended in D+R- kidney transplant recipients (KTR), but is associated with a theoretical increased risk of developing anti-CMV drug resistance. This hypothesis was retested in this study by comparing 32 D+R- KTR who received 3 months prophylaxis (valganciclovir) with 80 D+R- KTR who received preemptive treatment. The incidence of CMV infections was higher in the preemptive group than in the prophylactic group (60% vs. 34%, respectively; p = 0.02). Treatment failure (i.e. a positive DNAemia 8 weeks after the initiation of anti-CMV treatment) was more frequent in the preemptive group (31% vs. 3% in the prophylactic group; p = 0.001). Similarly, anti-CMV drug resistance (UL97 or UL54 mutations) was also more frequent in the preemptive group (16% vs. 3% in the prophylactic group; p = 0.05). Antiviral treatment failures were associated with anti-CMV drug resistance (p = 0.0001). Patients with a CMV load over 5.25 log(10)  copies/mL displayed the highest risk of developing anti-CMV drug resistance (OR = 16.91, p = 0.0008). Finally, the 1-year estimated glomerular filtration rate was reduced in patients with anti-CMV drug resistance (p = 0.02). In summary, preemptive therapy in D+R- KTR with high CMV loads and antiviral treatment failure was associated with a high incidence of anti-CMV drug resistance.
authors.affiliation: Centre Hospitalier Universitaire de Bordeaux, Hôpital Pellegrin, 33076 Bordeaux, France. lionel.couzi@chu-bordeaux.fr
authors.forename: L
authors.initials: L
authors.lastname: Couzi
authors.forename: S
authors.initials: S
authors.lastname: Helou
authors.forename: T
authors.initials: T
authors.lastname: Bachelet
authors.forename: K
authors.initials: K
authors.lastname: Moreau
authors.forename: S
authors.initials: S
authors.lastname: Martin
authors.forename: D
authors.initials: D
authors.lastname: Morel
authors.forename: M E
authors.initials: ME
authors.lastname: Lafon
authors.forename: B
authors.initials: B
authors.lastname: Boyer
authors.forename: S
authors.initials: S
authors.lastname: Alain
authors.forename: I
authors.initials: I
authors.lastname: Garrigue
authors.forename: P
authors.initials: P
authors.lastname: Merville
mesh_terms: D003587:Cytomegalovirus / Q000187:drug effects*; D024882:Drug Resistance, Viral; D006801:Humans; D015994:Incidence; D016030:Kidney Transplantation