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American Journal of Transplantation 12, 1 (2012) 202-9
High incidence of anticytomegalovirus drug resistance among D+R- kidney transplant recipients receiving preemptive therapy.
L. Couzi, S. Helou, T. Bachelet, K. Moreau, S. Martin1, D. Morel, M. E. Lafon, B. Boyer2, S. Alain3, I. Garrigue4, P. Merville

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.
1:  LBP - Laboratoire de Biophotonique et Pharmacologie - UMR 7213
2:  IPNO - Institut de Physique Nucléaire d'Orsay
3:  Teaching hospital
4:  MCMP - Microbiologie cellulaire et moléculaire et pathogénicité
Life Sciences/Microbiology and Parasitology