Incidence and factors associated with Herpes Zoster infection in kidney transplant recipients, a recent epidemiological study

Abstract

Herpes zoster (HZ), resulting from varicella-zoster virus reactivation, occurs more frequently 18 in immunocompromised patients, including kidney transplant recipients (KTRs). However, 19 contemporary epidemiological data focusing on age-specific incidence and risk factors in 20 homogeneous cohorts of KTRs remain limited (1)(2)(3)(4)(5)(6). 21We conducted a monocentric observational cohort study including all adult patients who 22 underwent kidney transplantation at our center between 2004 and 2015, had a functioning graft 23 at day 30, and received a standard immunosuppressive regimen based on a calcineurin inhibitor 24 combined with mycophenolate or everolimus. Patients with multi-organ transplantation or HIV 25 infection were excluded. Follow-up extended until January 2017, death, or graft failure. 26Cytomegalovirus prophylaxis consisted of valganciclovir for 3 or 6 months according to donor 27 and recipient serostatus, or a preemptive strategy. 28 Herpes zoster cases were identified through a systematic keyword search of shared electronic 29 medical records and validated by expert review based on clinical description; virological 30 confirmation was required only for disseminated or organ-invasive disease. Incidence rates 31 were calculated overall and by age group, with 95% confidence intervals obtained by bootstrap 32 resampling. Cumulative incidence was estimated using the Aalen-Johansen method, 33 accounting for death and graft failure as competing events. Risk factors for HZ were evaluated 34 using cause-specific Cox proportional hazards models, with valganciclovir exposure modeled 35 as a time-varying covariate. Variables associated with HZ at p<0.20 in univariable analyses with p<0.05, after colinearity checking. 38 A total of 1101 KTRs were included, with a median follow-up of 5.6 [3.3-9.2] years, 39 representing 6092 patient-years. Eighty-nine patients experienced at least one episode of HZ, 40 yielding an incidence rate of 14.5 per 1000 patient-years (95% CI: 11.5-17.6). The median time 41 to HZ onset was 5.3 years post-transplantation Among the 99 zoster herpes, 20 were severe 42 (22.5% ; ophtalmic or neurological involvment, post-herpetic neuralgia, disseminated VZV, 43 tissue invasive/organ disease), 53 non severe (59.5% ); and 16 undetermined (18%). 44Recipients who developed HZ were older at transplantation (p=0.042), had a higher number of 45 HLA class II mismatches (p=3.2×10⁻⁴), and were more likely to receive maintenance