*Purpose: Current consensus guidelines for CMV prevention recommend valganciclovir (VGCV) prophylaxis for 3 months after transplantation for CMV R+ kidney transplant recipients (KTR). This standard risk assessment does not account for factors other than CMV serostatus that may confer a higher risk for CMV infection.

*Methods: We conducted a retrospective chart review of adult (≥ 18 years old) CMV R+ KTR from 2/1/2013 to 12/31/2016 who received at least 6 months of follow up after completing low-dose VGCV prophylaxis. We collected data on demographics, clinical characteristics, transplant-related parameters, and occurrence of CMV infection. CMV viremia was defined as a viral load of ≥1000 copies/mL or ≥900IU/mL. We used standard definitions for CMV syndrome and disease. A stepwise multivariate logistic regression model was used to identify factors independently associated with CMV infection including black race, age ≥65, re-transplantation, panel reactive antibodies >10%, donor-specific antibodies, and acute cellular rejection (ACR).

*Results: A total of 206 R+ KTR met inclusion criteria. The median age was 53 [IQR 42-62], 63% were male and 62% were Caucasian race. Anti-thymocyte globulin (48%), alemtuzumab (37%) and basiliximab (15%) were used for induction therapy. The median duration of CMV prophylaxis was 90 days [IQR 88-112]. Twenty-four (11.6%) KTR developed CMV infection at a median of 159 days post-transplant, including asymptomatic viremia (n=14), CMV syndrome (n=5), and CMV disease (2 multi-organ involvement, 2 retinitis, 2 colitis, 1 nephritis). ACR occurred in 39 (19%) and death-censored graft loss in 6 (3%). In a multivariate analysis, ACR was strongly associated with CMV infection with an OR of 5.7 [CI 2.2-15.0; p<0.0004]. Age ≥ 65, black race, re-transplantation, panel reactive antibodies >10%, and donor-specific antibodies were not associated with an increased risk for CMV infection. Every additional month of CMV prophylaxis was associated with a 45% decreased likelihood of developing CMV infection during the study period, with a monthly unit OR 0.45 [CI 0.21-0.96; p=0.0085]

*Conclusions: Only ACR was associated with an increased risk for CMV infection in R+ KTR. Regardless of specific risk factors, every additional month of CMV prophylaxis was associated with a significant decrease in the likelihood of developing CMV infection, an effect that extended beyond the recommended 3 month prophylaxis period. Future studies are required to determine the optimal duration of prophylaxis for R+ KTR.

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