*Purpose: To assess the impact of cytomegalovirus (CMV) targeted antiviral prophylaxis on the development of herpes simplex (HSV) and varicella zoster (VZV) infections after kidney transplantation.

*Methods: This single center retrospective analysis at a large academic medical center included 987 patients who underwent kidney transplant between 1/1/2012 and 12/31/2018. Per institutional protocol, patients who were both CMV IgG recipient (R) and donor (D) seronegative or those who did not receive T-cell depleting induction therapy at the time of transplant received no antiviral prophylaxis thereafter. Those who were CMV R+ and received T-cell depleting induction or D+/R- received 3 or 6 months of valganciclovir (VGC) prophylaxis, respectively, with a target dose of 450 mg by mouth daily with appropriate renal adjustment. The primary outcome was a composite of HSV and VZV infection within the first 3 months after transplantation, defined as a prescription order for acyclovir or valacyclovir at appropriate treatment dosing regimens with confirmed therapeutic indication via chart review.

*Results: HSV or VZV infection occurred in 6/688 (0.9%) of those who received VGC and 8/299 (2.7%) of those who did not receive prophylaxis at 3 months (p=0.055). There was a significant difference in HSV infection risk at 3 months between the groups (0.3% vs. 2.0%, p=0.011) (Table 1). No difference was seen in HSV or VZV infections at 6 months (Table 2).

*Conclusions: Antiviral prophylaxis with VGC was associated with a decreased risk of HSV infections within the first 3 months after kidney transplantation with little effect on the development of VZV infections. These results indicate that VGC is effective at preventing both CMV and HSV infections in the early post-transplant period, therefore kidney transplant recipients not receiving antiviral prophylaxis with VGC, acyclovir or valacyclovir prophylaxis is warranted to mitigate risk of HSV emergence.

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