B367 - Incidence of Breakthrough CMV Infection in High-Risk (CMV D+R-) Kidney Transplant Patients Receiving Reduced-Dose Valganciclovir Prophylaxis

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Author Block: M. Strausbaugh, J. Mikolay Jr, J. Bleau, K. Yadav, B. W. Khalil, University of Toledo Medical Center, Toledo, OH
*Purpose: Cytomegalovirus (CMV) is a common opportunistic infection in kidney transplant recipients. Seronegative recipients (R-) receiving organs from seropositive donors (D+) face the highest risk. Valganciclovir (VG) 900 mg daily is the guideline-recommended dose for prophylaxis, though emerging data suggest that 450 mg daily may provide similar efficacy with fewer adverse effects and lower cost. This study evaluates the incidence of breakthrough CMV infection among high-risk recipients receiving reduced-dose valganciclovir.
*Methods: This retrospective chart review included kidney transplant recipients at the University of Toledo Medical Center between October 1, 2022, and July 1, 2024. Patients ≥18 years old with D+/R- serostatus who received valganciclovir 450 mg daily for six months post-transplant were included. Exclusion criteria were pregnancy, prior CMV viremia, multi-organ transplant, or use of non-valganciclovir prophylaxis. The primary endpoint was incidence of breakthrough CMV infection. Secondary endpoints included rates of recurrent CMV, tissue-invasive CMV disease, leukopenia, valganciclovir dose adjustments based on renal function, treatment regimens for initial infection, and development of resistant or refractory CMV.
*Results: Of 195 screened patients, 92 met inclusion criteria and 87 were ultimately included. Among patients maintained on full-dose valganciclovir 450 mg daily with CrCl >60 mL/min, breakthrough infection occurred in 21% (8/38). Two patients (25%) demonstrated tissue-invasive disease. Induction immunosuppression included alemtuzumab (n=5) and thymoglobulin (n=2). Among patients who experienced dose reductions due to renal function adjustment or leukopenia (n=10), 11.5% developed breakthrough infections. One case (10%) followed inappropriate renal dose reduction, while nine cases (90%) followed dose reduction for leukopenia. Three patients (30%) showed tissue-invasive features. Induction agents included alemtuzumab (n=3), basiliximab (n=2), and thymoglobulin (n=5).
*Conclusions: Valganciclovir dose reductions in patients with CrCl >60 mL/min or adjustments due to leukopenia were associated with increased breakthrough CMV viremia. Strengthening renal dosing protocols, optimizing leukopenia management, and validating standardized dosing algorithms may reduce breakthrough infections in this high-risk population.