Preventive Strategies Against Cytomegalovirus and Incidence of α-Herpesvirus Infections in Solid Organ Transplant Recipients: A Nationwide Cohort Study

Abstract

We assessed the impact of antiviral preventive strategies on the incidence of herpes simplex virus (HSV) and varicella-zoster virus (VZV) infections in a nationwide cohort of transplant recipients. Risk factors for the development of HSV or VZV infection were assessed by Cox proportional hazards regression. We included 2781 patients (56% kidney, 20% liver, 10% lung, 7.3% heart, 6.7% others). Overall, 1264 (45%) patients received antiviral prophylaxis (ganciclovir or valganciclovir, n = 1145; acyclovir or valacyclovir, n = 138). Incidence of HSV and VZV infections was 28.9 and 12.1 cases, respectively, per 1000 person-years. Incidence of HSV and VZV infections at 1 year after transplant was 4.6% (95% confidence interval [CI] 3.5-5.8) in patients receiving antiviral prophylaxis versus 12.3% (95% CI 10.7-14) in patients without prophylaxis; this was observed particularly for HSV infections (3% [95% CI 2.2-4] versus 9.8% [95% CI 8.4-11.4], respectively). A lower rate of HSV and VZV infections was also seen in donor or recipient cytomegalovirus-positive patients receiving ganciclovir or valganciclovir prophylaxis compared with a preemptive approach. Female sex (hazard ratio [HR] 1.663, p = 0.001), HSV seropositivity (HR 5.198, p < 0.001), previous episodes of rejection (HR 1.95, p = 0.004), and use of a preemptive approach (HR 2.841, p = 0.017) were significantly associated with a higher risk of HSV infection. Although HSV and VZV infections were common after transplantation, antiviral prophylaxis significantly reduced symptomatic HSV infections.

Herpes zoster in kidney transplant recipients: protective effect of anti-cytomegalovirus prophylaxis and natural killer cell count. A single-center cohort study

“…In addition, some studies directly compared the effect of prophylaxis with anti‐CMV and anti‐HSV agents, reporting a nonsignificant trend toward a lower incidence of HZ among KT recipients under (val‐)GCV as compared to those receiving acyclovir or its derivatives . However, the administration of specific anti‐HSV prophylaxis among CMV D−/R− patients in daily clinical practice is far from universal . Of note, none of our patients that were not subjected to anti‐CMV prophylaxis received acyclovir or any of its derivatives to prevent α‐herpesvirus infection, regardless of their CMV D/R serostatus.…”

“…Acute graft rejection has been found to increase the risk of HZ in some but not all previous studies. Interestingly, after incorporating death and graft loss as competing risk events in the regression model, we found no apparent impact of such a complication on the occurrence of either early or late HZ.…”

“…It has been accordingly proposed that SOT recipients already receiving (val‐)GCV to prevent CMV infection may be safely spared specific prophylaxis with acyclovir or it prodrugs against herpes simplex virus (HSV) or VZV . However, clinical data supporting this recommendation is relatively scarce, in particular regarding HZ, and the results from various studies have been not entirely conclusive . A recent subanalysis from the Swiss Transplant Cohort Study (STCS) found that SOT recipients on anti‐CMV prophylaxis had a lower incidence of overall infection due to α‐herpesviruses (mainly HSV), although this protective effect could not be specifically proven for HZ despite the large number of patients included .…”

“…However, clinical data supporting this recommendation is relatively scarce, in particular regarding HZ, and the results from various studies have been not entirely conclusive . A recent subanalysis from the Swiss Transplant Cohort Study (STCS) found that SOT recipients on anti‐CMV prophylaxis had a lower incidence of overall infection due to α‐herpesviruses (mainly HSV), although this protective effect could not be specifically proven for HZ despite the large number of patients included . Other authors have been unable to ascertain the impact of anti‐CMV agents on the incidence of post‐transplant HZ, either due to the universal use of (val‐)GCV prophylaxis in the analyzed cohort or to the lack of specific data .…”

“…Previous studies focused on HZ among KT recipients were performed more than 15 years ago (limiting its applicability to contemporary immunosuppression practices) , jointly considered different SOT populations or suffer from short post‐transplant follow‐up or lack of data granularity . Most importantly, none of them investigated any surrogate of the VZV‐specific host's immune response.…”