*Purpose: To compare the rate of CMV viremia and invasive disease in kidney transplantation patients with a de-novo belatacept (bela) regimen vs. a no-bela maintenance immunosuppression regimen.

*Methods: Patients who underwent kidney transplantation at one academic medical center between 2015 and 2021 were divided into two groups based on maintenance immunosuppression regimens: standard dose mycophenolate, rapamune, and tacrolimus vs. low-dose mycophenolate, low-dose tacrolimus, and belatacept (5.0 mg/kg monthly). All patients at risk for CMV disease received standard antiviral prophylaxis with oral valganciclovir. Recipient and donor demographic information was compared and CMV infection between groups was assessed by occurrence of CMV viremia, invasive CMV disease, time to CMV viremia, maximum CMV PCR (copies/mL), and time to CMV clearance. Invasive CMV disease was defined as end-organ damage (i.e. enteritis, pneumonitis, hepatitis, retinitis).

*Results: 246 no bela vs. 119 bela patients were identified. High-risk status for primary CMV disease (21.1% vs. 25.2%, p=.34) and rates of CMV viremia (11.4% vs. 15.1%, p=.31) were not significantly different between no bela and bela groups, respectively. Most infections occurred in patients at high-risk for primary CMV disease in no bela and bela groups, respectively (85.7% vs. 88.9%). However, bela patients experienced higher maximum PCR levels compared with no bela, respectively (median: 18,100 vs. 3,660), but did not reach statistical significance (p=.09). Bela treatment was associated with significantly higher rates of invasive CMV disease compared with no bela, respectively (27.8% vs. 3.6%, p<.001). Additionally, bela was associated with longer time to clearance of CMV viremia (mean days: 199 vs. 91, p=.04). There was no difference in the onset of CMV viremia between groups (mean days: 307 bela vs. 287 no bela, p=.70), likely due to CMV prophylaxis.

*Conclusions: Belatacept is a novel immunosuppressive drug that is becoming more involved in long-term drug regimens following kidney transplantation. Development of CMV viremia is a well-recognized complication of immunosuppression therapy but data regarding CMV infection with use of de-novo belatacept is lacking. These data suggest that de-novo belatacept therapy in patients at risk for primary CMV disease is associated with a significantly higher rate of invasive CMV disease and lengthier time to clearance of viremia. Therefore, after completion of CMV prophylaxis regimens, belatacept-treated patients may benefit from intense post-operative monitoring and treatment.

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