This study is being done to compare the effectiveness of de novo Letermovir versus valganciclovir in preventing the development of cytomegalovirus viremia or symptomatic disease in African American kidney transplant recipients within the first year after transplantation.

There are two arms in the study:

Arm 1: Prophylaxis: This group includes freshly transplanted high risk (CMV D+/R-) African American Kidney recipients who will be on prophylactic Letermovir for 6 month.

Arm 2: Prophylaxis: This group includes high-risk African American kidney transplant recipients who had already completed the 6 month prophylactic course with the standard of care Valganciclovir.

Valganciclovir (VGC) is the drug of choice for CMV prophylaxis. Although effective in preventing CMV infections, VGC is commonly associated with profound bone marrow suppression, specifically leukopenia which increases patients' vulnerability to other infections. Moreover, kidney transplant recipients often receive lymphocytic antibody therapy for induction immunosuppression, which further exacerbates the risk of leukopenia in the first 3-6 months after transplantation. The high leukopenia burden makes management of immunosuppression in the post-transplant setting more complex, often necessitating reduction in immunosuppressive agents that increases risk of allograft rejection.

Primary Objective: this study is being done to compare the effectiveness of de novo Letermovir versus the standard of care valganciclovir in preventing the development of cytomegalovirus viremia (defined as CMV PCR > 137 units/ml) or symptomatic disease in AA kidney transplant recipients within the first year after transplantation.

Secondary Objectives: included leukopenia incidence, acute rejection rates, breakthrough CMV rates, mycophenolate dose adjustments, donor-specific antibody formation, and tolerability.

To compare these these two groups the study uses

• Intervention Letermovir: Recipients in this group will be on prophylactic Letermovir 480mg once a day pill started within the first 5 days of post-transplant up until 6 months post-transplant. Given Letermovir has no activity against herpes viruses, solid organ transplant recipients are at risk of herpes simplex viruses. Participants enrolled in this study group will also receive prophylactic acyclovir 400mg twice daily for the duration of their Letermovir treatment. Both Letermovir and study mandated medication (Acyclovir) are already approved for use by the FDA.
• Intervention Valganciclovir- In this group recipients who have historically received the standard of care prophylactic valganciclovir will be assessed retrospectively. Valganciclovir is 450mg once a day pill started with in the first 10 days post-transplant or at the time of discharge after kidney transplant and taken up until 6 month post-transplant. This historical control study group will include high-risk African American kidney transplant recipients identified from prior research studies who were cared for with Valganciclovir in the 5 years prior to the enrollment start for the study group.

Outcomes of these two groups will be compared in 1:1 fashion. The study will attempt to match patients on Letermovir to the historical patients who received valganciclovir, based on age, kidney Donor profile index and the presence of panel of reactive antibodies.

Strategy for CMV Viremia: CMV viremia will be treated with either oral valganciclovir, intravenous ganciclovir or alternative agents, according to AST ID COP (American Society of Transplantation Infectious disease community of practice) guidelines.

Historical Control group:

Inclusion Criteria

1. Kidney transplant recipients
2. Male or female age ≥ 18 years old
3. African American race
4. CMV high risk (D+/R-)
5. received valganciclovir for CMV prophylaxis

Historical Control group:

Exclusion

1. Re-transplantation
2. Panel of reactive antibody ≥80% at the time of transplant
3. Positive cytotoxic cross match at the time of transplant

Experimental Group Inclusion Criteria

1. Kidney transplant recipients
2. Male or female age ≥ 18 years old
3. African American race
4. CMV high risk (D+/R-)
5. Ability to provide informed consent before any trial related activities

Exclusion Criteria

1. Re-transplantation
2. Panel of reactive antibody ≥80% at the time of transplant
3. Positive cytotoxic cross match at the time of transplant
4. Pregnancy and Breastfeeding
5. Prisoners
6. Patients with hypersensitivity to acyclovir, valacyclovir or any of its components
7. Patients with hypersensitivity to Letermovir or any of its components
8. If Patients are taking any of these medications: pimozide, ergot alkaloids (ergotamine, dihydroergotamine), or pitavastatin/simvastatin co-administered with cyclosporine, we will work with the prescribing physician to find an appropriate replacement therapy which will not interfere with any study-related interventions. Otherwise, participants will be excluded from the study.