title: Easier Control of Late-Onset Cytomegalovirus Disease Following Universal Prophylaxis Through an Early Antiviral Immune Response in Donor-Positive, Recipient-Negative Kidney Transplants.
abstract: Universal prophylaxis for cytomegalovirus (CMV) prevention is viable but, compared with a preemptive strategy, leads to higher incidence of late-onset disease (LOD) associated with poor patient and graft survival. The purpose of this study was to compare LOD with early onset disease (EOD), with a focus on the highest risk kidney transplant recipients (KTRs): CMV seronegative recipients transplanted from seropositive donors (D+R-). Since CMV control depends on both antiviral treatment and specific immune response, we also compared Vδ2-negative (Vδ2(neg) ) γδ T cell expansion involved in CMV infection resolution. EOD was defined as occurring <3 mo and LOD as occurring >3 mo after transplantation. Depending on the period, universal prophylaxis or preemptive treatment was used. Overall, 168 D+R- KTRs were included between 2003 and 2011. LOD was associated with a lower peak DNAemia (p = 0.04), fewer recurrences (odds ratio 0.16; 95% confidence interval 0.05-0.55; p = 0.01) and shorter anti-CMV curative treatment (40 vs. 60 days, p < 0.0001). As a corollary, we found that Vδ2(neg) γδ T cell expansion was faster in LOD than in EOD (31 vs. 168 days after the beginning of CMV disease, p < 0.0001). In D+R- KTRs, universal prophylaxis is associated with more LOD, which had better infection management and a faster immune response. These results support the use of universal prophylaxis over a preemptive strategy and reappraise outcomes of LOD.
authors.affiliation: Department of Nephrology, Transplantation and Dialysis, Bordeaux, France.
authors.forename: H
authors.initials: H
authors.lastname: Kaminski
authors.affiliation: Department of Nephrology, Transplantation and Dialysis, Bordeaux, France.|National Center of Scientific Research (CNRS), Research Unit 5234, Bordeaux, France.
authors.forename: L
authors.initials: L
authors.lastname: Couzi
authors.affiliation: Virology Laboratory, Bordeaux, France.|National Center of Scientific Research, Mix Unit of Research 5164, Bordeaux, France.
authors.forename: I
authors.initials: I
authors.lastname: Garrigue
authors.affiliation: National Center of Scientific Research (CNRS), Research Unit 5234, Bordeaux, France.|Immunology Laboratory, Pellegrin Hospital, Bordeaux, France.
authors.forename: J-F
authors.initials: JF
authors.lastname: Moreau
authors.affiliation: National Center of Scientific Research (CNRS), Research Unit 5234, Bordeaux, France.
authors.forename: J
authors.initials: J
authors.lastname: Déchanet-Merville
authors.affiliation: Department of Nephrology, Transplantation and Dialysis, Bordeaux, France.|National Center of Scientific Research (CNRS), Research Unit 5234, Bordeaux, France.
authors.forename: P
authors.initials: P
authors.lastname: Merville
mesh_terms: D017668:Age of Onset; D000998:Antiviral Agents / Q000494:pharmacology*; D003587:Cytomegalovirus / Q000276:immunology*; D003586:Cytomegalovirus Infections / Q000188:drug therapy / Q000276:immunology* / Q000821:virology; D005260:Female; D005500:Follow-Up Studies; D005919:Glomerular Filtration Rate; D006085:Graft Survival / Q000187:drug effects / Q000276:immunology*; D006801:Humans; D007676:Kidney Failure, Chronic / Q000601:surgery*; D007677:Kidney Function Tests; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012189:Retrospective Studies; D012307:Risk Factors; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D014019:Tissue Donors
chemical_list: D000998:Antiviral Agents
keywords: clinical research/practice; complication: infectious; immunobiology; infection and infectious agents; infectious disease; kidney transplantation/nephrology; monitoring: immune; recurrent disease; translational research/science; viral: Cytomegalovirus (CMV)