Immunoguided Discontinuation of Prophylaxis for Cytomegalovirus Disease in Kidney Transplant Recipients Treated With Antithymocyte Globulin: A Randomized Clinical Trial


Por: Paez-Vega, A, Gutierrez-Gutierrez, B, Aguera, ML, Facundo, C, Redondo-Pachon, D, Suner, M, Lopez-Oliva, MO, Yuste, JR, Montejo, M, Galeano-Alvarez, C, Ruiz-San Millan, JC, Los-Arcos, I, Hernandez, D, Fernandez-Ruiz, M, Munoz, P, Valle-Arroyo, J, Cano, A, Rodriguez-Benot, A, Crespo, M, Rodelo-Haad, C, Lobo-Acosta, MA, Garrido-Gracia, JC, Vidal, E, Guirado, L, Cantisan, S, Torre-Cisneros, J

Publicada: 9 mar 2022 Ahead of Print: 1 ago 2021
Resumen:
Background Antiviral prophylaxis is recommended in cytomegalovirus (CMV)-seropositive kidney transplant (KT) recipients receiving antithymocyte globulin (ATG) as induction. An alternative strategy of premature discontinuation of prophylaxis after CMV-specific cell-mediated immunity (CMV-CMI) recovery (immunoguided prevention) has not been studied. Our aim was to determine whether it is effective and safe to discontinue prophylaxis when CMV-CMI is detected and to continue with preemptive therapy. Methods In this open-label, noninferiority clinical trial, patients were randomized 1:1 to follow an immunoguided strategy, receiving prophylaxis until CMV-CMI recovery or to receive fixed-duration prophylaxis until day 90. After prophylaxis, preemptive therapy (valganciclovir 900 mg twice daily) was indicated in both arms until month 6. The primary and secondary outcomes were incidence of CMV disease and replication, respectively, within the first 12 months. Desirability of outcome ranking (DOOR) assessed 2 deleterious events (CMV disease/replication and neutropenia). Results A total of 150 CMV-seropositive KT recipients were randomly assigned. There was no difference in the incidence of CMV disease (0% vs 2.7%; P = .149) and replication (17.1% vs 13.5%; log-rank test, P = .422) between both arms. Incidence of neutropenia was lower in the immunoguided arm (9.2% vs 37.8%; odds ratio, 6.0; P < .001). A total of 66.1% of patients in the immunoguided arm showed a better DOOR, indicating a greater likelihood of a better outcome. Conclusions Prophylaxis can be prematurely discontinued in CMV-seropositive KT patients receiving ATG when CMV-CMI is recovered since no significant increase in the incidence of CMV replication or disease is observed. In cytomegalovirus (CMV)-seropositive kidney transplant recipients receiving ATG induction, immunoguided prevention is not inferior to prophylaxis to prevent CMV complications. Prophylaxis can be prematurely discontinued after CMV-cell-mediated immunity recovery with no significant increase in the incidence of CMV replication or disease.

Filiaciones:
Paez-Vega, A:
 Univ Cordoba UCO, Reina Sofia Univ Hosp, Maimonides Inst Biomed Res Cordoba IMIBIC, Cordoba, Spain

 Inst Salud Carlos III, Spanish Network Res Infect Dis, Madrid, Spain

Gutierrez-Gutierrez, B:
 Inst Salud Carlos III, Spanish Network Res Infect Dis, Madrid, Spain

 Univ Seville, Virgen Macarena Univ Hosp, Biomed Inst Seville IBiS, Clin Unit Infect Dis Microbiol & Prevent Med, Seville, Spain

Aguera, ML:
 Univ Cordoba UCO, Reina Sofia Univ Hosp, Maimonides Inst Biomed Res Cordoba IMIBIC, Cordoba, Spain

 Reina Sofia Univ Hosp, Nephrol Serv, Cordoba, Spain

Facundo, C:
 Autonomous Univ Barcelona UAB, Nephrol Serv, Inst Invest Biosanitaria St Pau, Fundacio Puigvert,Renal Transplant Unit, Barcelona, Spain

Redondo-Pachon, D:
 Hosp del Mar, Hosp del Mar Med Res Inst IMIM, Nephrol Serv, Barcelona, Spain

Suner, M:
 Virgen del Rocio Univ Hosp, Nephrol Serv, Seville, Spain

Lopez-Oliva, MO:
 La Paz Univ Hosp, Nephrol Serv, Madrid, Spain

Yuste, JR:
 Inst Salud Carlos III, Spanish Network Res Infect Dis, Madrid, Spain

 Clin Univ Navarra, Infect Dis Unit, Pamplona, Spain

Montejo, M:
 Inst Salud Carlos III, Spanish Network Res Infect Dis, Madrid, Spain

 Cruces Univ Hosp, Infect Dis Serv, Bilbao, Spain

Galeano-Alvarez, C:
 Ramon y Cajal Univ Hosp, IRYCIS, Nephrol Serv, Madrid, Spain

Ruiz-San Millan, JC:
 Univ Cantabria, Marques de Valdecilla Hosp, Nephrol Serv, IDIVAL, Santander, Spain

Los-Arcos, I:
 Inst Salud Carlos III, Spanish Network Res Infect Dis, Madrid, Spain

 Vall dHebron Univ Hosp, Infect Dis Serv, Barcelona, Spain

Hernandez, D:
 Univ Malaga, Carlos Haya Reg Univ Hosp, Inst Biomed Res Malaga IBIMA, Nephrol Serv, Malaga, Spain

Fernandez-Ruiz, M:
 Inst Salud Carlos III, Spanish Network Res Infect Dis, Madrid, Spain

 12 Octubre Univ Hosp, Hlth Res Inst Imas12, Infect Dis Unit, Madrid, Spain

Munoz, P:
 Gregorio Maranon Univ Hosp, Dept Clin Microbiol & Infect Dis, Madrid, Spain

 Gregorio Maranon Biomed Res Inst, Madrid, Spain

 Univ Complutense Madrid, Dept Med, Madrid, Spain

 CIBERES, Madrid, Spain

Valle-Arroyo, J:
 Univ Cordoba UCO, Reina Sofia Univ Hosp, Maimonides Inst Biomed Res Cordoba IMIBIC, Cordoba, Spain

 Inst Salud Carlos III, Spanish Network Res Infect Dis, Madrid, Spain

Cano, A:
 Univ Cordoba UCO, Reina Sofia Univ Hosp, Maimonides Inst Biomed Res Cordoba IMIBIC, Cordoba, Spain

 Inst Salud Carlos III, Spanish Network Res Infect Dis, Madrid, Spain

Rodriguez-Benot, A:
 Univ Cordoba UCO, Reina Sofia Univ Hosp, Maimonides Inst Biomed Res Cordoba IMIBIC, Cordoba, Spain

 Reina Sofia Univ Hosp, Nephrol Serv, Cordoba, Spain

Crespo, M:
 Hosp del Mar, Hosp del Mar Med Res Inst IMIM, Nephrol Serv, Barcelona, Spain

Rodelo-Haad, C:
 Univ Cordoba UCO, Reina Sofia Univ Hosp, Maimonides Inst Biomed Res Cordoba IMIBIC, Cordoba, Spain

 Reina Sofia Univ Hosp, Nephrol Serv, Cordoba, Spain

Lobo-Acosta, MA:
 Virgen del Rocio Univ Hosp CTU HUVR, Clin Trials Unit, Seville, Spain

Garrido-Gracia, JC:
 Univ Cordoba, Reina Sofia Univ Hosp, Maimonides Inst Biomed Res Cordoba IMIBIC, Clin Trials Unit, Cordoba, Spain

Vidal, E:
 Univ Cordoba UCO, Reina Sofia Univ Hosp, Maimonides Inst Biomed Res Cordoba IMIBIC, Cordoba, Spain

 Inst Salud Carlos III, Spanish Network Res Infect Dis, Madrid, Spain

 Reina Sofia Univ Hosp, Infect Dis Serv, Cordoba, Spain

Guirado, L:
 Autonomous Univ Barcelona UAB, Nephrol Serv, Inst Invest Biosanitaria St Pau, Fundacio Puigvert,Renal Transplant Unit, Barcelona, Spain

Cantisan, S:
 Univ Cordoba UCO, Reina Sofia Univ Hosp, Maimonides Inst Biomed Res Cordoba IMIBIC, Cordoba, Spain

 Inst Salud Carlos III, Spanish Network Res Infect Dis, Madrid, Spain

Torre-Cisneros, J:
 Univ Cordoba UCO, Reina Sofia Univ Hosp, Maimonides Inst Biomed Res Cordoba IMIBIC, Cordoba, Spain

 Inst Salud Carlos III, Spanish Network Res Infect Dis, Madrid, Spain

 Reina Sofia Univ Hosp, Infect Dis Serv, Cordoba, Spain
ISSN: 10584838
Editorial
OXFORD UNIV PRESS INC, JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA, Estados Unidos America
Tipo de documento: Article
Volumen: 74 Número: 5
Páginas: 757-765
WOS Id: 000755830200001
ID de PubMed: 34228099
imagen Open Access

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