title: The effect of cidofovir on adenovirus plasma DNA levels in stem cell transplantation recipients without T cell reconstitution.
abstract: Cidofovir is frequently used to treat life-threatening human adenovirus (HAdV) infections in immunocompromised children after hematopoietic stem cell transplantation (HSCT). However, the antiviral effect irrespective of T cell reconstitution remains unresolved. Plasma HAdV DNA levels were monitored by real-time quantitative PCR during 42 cidofovir treatment episodes for HAdV viremia in 36 pediatric allogeneic HSCT recipients. HAdV load dynamics were related to T and natural killer (NK) cell reconstitution measured by flow cytometry. To evaluate the in vivo antiadenoviral effect of cidofovir, we focused on 20 cidofovir treatment episodes lacking concurrent T cell reconstitution. During 2 to 10 weeks of follow-up in the absence of T cells, HAdV load reduction (n = 7) or stabilization (n = 8) was observed in 15 of 20 treatments. Although HAdV load reduction was always accompanied by NK cell expansion, HAdV load stabilization was measured in 2 children lacking both T and NK cell reconstitution. In cases with T cell reconstitution, rapid HAdV load reduction (n = 14) or stabilization (n = 6) was observed in 20 of 22 treatments. In the absence of T cells, cidofovir treatment was associated with HAdV viremia control in the majority of cases. Although the contribution of NK cells cannot be excluded, cidofovir has the potential to mediate HAdV load stabilization in the time pending T cell reconstitution.
authors.affiliation: Department of Pediatrics, Leiden University Medical Center, Leiden, The Netherlands. Electronic address: g.lugthart@lumc.nl.
authors.forename: Gertjan
authors.initials: G
authors.lastname: Lugthart
authors.affiliation: Department of Pediatrics, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Marloes A
authors.initials: MA
authors.lastname: Oomen
authors.affiliation: Department of Pediatrics, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Cornelia M
authors.initials: CM
authors.lastname: Jol-van der Zijde
authors.affiliation: Department of Pediatrics, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Lynne M
authors.initials: LM
authors.lastname: Ball
authors.affiliation: Department of Pediatrics, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Dorine
authors.initials: D
authors.lastname: Bresters
authors.affiliation: Department of Pediatrics, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Wouter J W
authors.initials: WJ
authors.lastname: Kollen
authors.affiliation: Department of Pediatrics, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Frans J
authors.initials: FJ
authors.lastname: Smiers
authors.affiliation: Department of Pediatrics, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Clementien L
authors.initials: CL
authors.lastname: Vermont
authors.affiliation: Department of Pediatrics, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Robbert G M
authors.initials: RG
authors.lastname: Bredius
authors.affiliation: Department of Pediatrics, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Marco W
authors.initials: MW
authors.lastname: Schilham
authors.affiliation: Department of Pediatrics, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Maarten J D
authors.initials: MJ
authors.lastname: van Tol
authors.affiliation: Department of Pediatrics, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Arjan C
authors.initials: AC
authors.lastname: Lankester
mesh_terms: D000258:Adenovirus Infections, Human / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology / Q000821:virology; D000260:Adenoviruses, Human / Q000187:drug effects / Q000276:immunology; D000293:Adolescent; D000998:Antiviral Agents / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D000077404:Cidofovir; D015331:Cohort Studies; D003596:Cytosine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D004279:DNA, Viral / Q000037:antagonists & inhibitors* / Q000097:blood; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D016867:Immunocompromised Host; D007223:Infant; D007694:Killer Cells, Natural / Q000166:cytology / Q000276:immunology; D018655:Lymphocyte Count; D008212:Lymphocyte Depletion; D008297:Male; D063065:Organophosphonates / Q000627:therapeutic use*; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology; D014184:Transplantation, Homologous; D019562:Viral Load / Q000187:drug effects; D014766:Viremia / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology / Q000821:virology
chemical_list: D000998:Antiviral Agents; D004279:DNA, Viral; D063065:Organophosphonates; D003596:Cytosine; D000077404:Cidofovir
keywords: Cidofovir; Hematopoietic stem cell transplantation; Human adenovirus; Immune reconstitution; Natural killer cells; Pediatrics