title: Therapeutic effect of the acquisition of cytomegalovirus-specific immune response during preemptive treatment.
abstract: BACKGROUND
  It has been suggested that preemptive therapy against cytomegalovirus (CMV) infection after transplantation promotes a CMV-specific immune response. Our objective was to determine whether solid-organ transplant patients at high risk for CMV infection treated preemptively acquire a CMV-specific immune response and whether the acquired immune response confers immunity by controlling subsequent CMV replication episodes and by protecting from late-onset CMV disease.
  
  
  METHODS
  Patients were followed up for 18 months after transplantation. CMV viral load was determined using real-time polymerase chain reaction assays, and the T-cell immune response was characterized by intracellular cytokine staining.
  
  
  RESULTS
  The 21 patients studied developed CMV replication episodes at a median of 4 weeks (range 2-8 weeks) after transplantation and a CMV-specific T-cell response within a median of 12 weeks (range 10-20 weeks). The decline in the incidence of CMV replication episodes is inversely correlated with the acquisition of the CMV-specific T-cell response (linear regression r=0.781, Pearson correlation=-0.883; P=0.001). There were no CMV replication episodes after week 47 of transplantation. In addition, after acquisition of the immune response, 42 replication episodes were cleared without treatment. The time taken for immune clearance of replication correlated with the peak viral load (P=0.01). No incidence of CMV early or late-onset disease was detected.
  
  
  CONCLUSIONS
  Our results demonstrate that preemptive therapy is a safe and an effective strategy for the control of CMV infection in solid-organ transplant recipients at high risk for CMV infection. This is the first study that reports a therapeutic effect of the acquisition of CMV-specific immune response during preemptive treatment.
authors.affiliation: Unit of Infectious Diseases, Microbiology and Preventive Medicine/Instituto de Biomedicina de Sevilla (IBiS), University Hospital Virgen del Rocío/CSIC/University of Sevilla, Sevilla, Spain.
authors.forename: Omar J
authors.initials: OJ
authors.lastname: Benmarzouk-Hidalgo
authors.forename: José M
authors.initials: JM
authors.lastname: Cisneros
authors.forename: Elisa
authors.initials: E
authors.lastname: Cordero
authors.forename: Almudena
authors.initials: A
authors.lastname: Martín-Peña
authors.forename: Berta
authors.initials: B
authors.lastname: Sanchez
authors.forename: Cecilia
authors.initials: C
authors.lastname: Martin-Gandul
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Gentil
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Gomez-Bravo
authors.forename: Ernesto
authors.initials: E
authors.lastname: Lage
authors.forename: Pilar
authors.initials: P
authors.lastname: Perez-Romero
mesh_terms: D056704:Adaptive Immunity / Q000187:drug effects*; D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000008:administration & dosage*; D016207:Cytokines / Q000378:metabolism; D003587:Cytomegalovirus / Q000187:drug effects* / Q000235:genetics / Q000254:growth & development / Q000276:immunology; D003586:Cytomegalovirus Infections / Q000175:diagnosis / Q000276:immunology / Q000517:prevention & control*; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D016377:Organ Transplantation / Q000009:adverse effects*; D011446:Prospective Studies; D013030:Spain; D013601:T-Lymphocytes / Q000276:immunology / Q000821:virology; D013997:Time Factors; D016896:Treatment Outcome; D019562:Viral Load; D014779:Virus Replication
chemical_list: D000998:Antiviral Agents; D016207:Cytokines; D007166:Immunosuppressive Agents