Epstein-Barr and Other Herpesvirus Infections in Patients With Early Onset Type 1 Diabetes Treated With Daclizumab and Mycophenolate Mofetil

The use of mycophenolate mofetil with or without daclizumab was generally safe in treatment of early onset type 1 diabetes. Epstein-Barr virus reactivations were equally common across treatment groups, but cumulative viral burdens tended to be higher in subjects receiving double-active versus double-placebo treatment. 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. Clinical Trials Registration. NCT00100178.