title: Epstein-Barr and other herpesvirus infections in patients with early onset type 1 diabetes treated with daclizumab and mycophenolate mofetil.
abstract: BACKGROUND
  We assessed the morbidity of herpesviruses in patients with type 1 diabetes mellitus (T1D) enrolled in immunosuppressive treatment studies.
  
  
  METHODS
  Epstein-Barr virus (EBV), cytomegalovirus (CMV), herpes simplex virus (HSV), and varicella zoster virus (VZV) infections were monitored in 126 participants of a randomized, double-blind, placebo-controlled study of daclizumab (DZB) and mycophenolate mofetil (MMF) including DZB(+)MMF(+), DZB(-)MMF(+), DZB(+)MMF(-), and DZB(-)MMF(-). During the 2-year follow-up, herpesviral infections were monitored clinically, by serology and blood DNA polymerase chain reaction.
  
  
  RESULTS
  Among 57 baseline EBV-seronegative participants, 9 developed EBV primary infections, including 2 with infectious mononucleosis syndrome. There were no appreciable differences in the course of the primary EBV infections across treatment groups. Among 69 baseline EBV-seropositive participants, 22 had virologic reactivations, including 1 symptomatic DZB(-)MMF(+) subject. Compared with 7 DZB(-)MMF(-) EBV reactivators, the 9 DZB(+)MMF(+) reactivators tended to have more prolonged viremia (11.4 vs 4.4 months; P = .06) and higher cumulative viral burden (14.2 vs 12.5 log EBV copies/mL; P = .06). Four of 85 baseline CMV-seronegative subjects developed asymptomatic primary CMV infections. There were no CMV reactivations. Of 30 baseline HSV-seropositive subjects, 8 developed ≥1 episode of herpes labialis; 1 subject had a primary HSV infection; and 1 subject without baseline serology information had a new diagnosis of genital HSV. There were no significant differences in the incidence of HSV recurrences across treatment groups. Of 100 baseline VZV-seropositive subjects, 1 DZB(-)MMF(-) subject developed herpes zoster and 1 DZB(-)MMF(+) subject had Bell's palsy possibly related to VZV.
  
  
  CONCLUSIONS
  The use of DZB alone or in combination with MMF was not associated with increased morbidity due to herpesviruses.
  
  
  BACKGROUND
  NCT00100178.
authors.affiliation: Children's National Medical Center, Washington, DC, USA.
authors.forename: Brett J
authors.initials: BJ
authors.lastname: Loechelt
authors.forename: David
authors.initials: D
authors.lastname: Boulware
authors.forename: Michael
authors.initials: M
authors.lastname: Green
authors.forename: Lindsey R
authors.initials: LR
authors.lastname: Baden
authors.forename: Peter
authors.initials: P
authors.lastname: Gottlieb
authors.forename: Heidi
authors.initials: H
authors.lastname: Krause-Steinrauf
authors.forename: Adriana
authors.initials: A
authors.lastname: Weinberg
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D061067:Antibodies, Monoclonal, Humanized / Q000009:adverse effects* / Q000627:therapeutic use; D002648:Child; D003587:Cytomegalovirus / Q000235:genetics / Q000276:immunology; D000077561:Daclizumab; D003922:Diabetes Mellitus, Type 1 / Q000150:complications* / Q000188:drug therapy; D020031:Epstein-Barr Virus Infections / Q000209:etiology* / Q000276:immunology; D005260:Female; D006564:Herpesviridae / Q000235:genetics / Q000276:immunology; D006566:Herpesviridae Infections / Q000209:etiology* / Q000276:immunology; D004854:Herpesvirus 4, Human / Q000235:genetics / Q000276:immunology; D006801:Humans; D007074:Immunoglobulin G / Q000009:adverse effects* / Q000627:therapeutic use; D007166:Immunosuppressive Agents / Q000009:adverse effects* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D014775:Virus Activation; D055815:Young Adult
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D007074:Immunoglobulin G; D007166:Immunosuppressive Agents; D000077561:Daclizumab; D009173:Mycophenolic Acid