Kidney Transplant Preemptive Therapy or Prophylaxis for CMV Prevention in D+R Recipients

Inclusion Criteria: 1. Subject or legally authorized representative has provided written informed consent. 2. Age ≥ 18 years of age at the time of informed consent. 3. Negative for IgG antibody to CMV as assessed in a CLIA-certified laboratory between 28 days prior to transplant and up to 7 days post-transplant but prior to randomization. 4. Received a kidney transplant from a CMV seropositive (IgG positive) donor in the past 7 days prior to enrollment 5. Individuals of reproductive (childbearing) potential must have a negative pregnancy test (serum or urine) collected prior to randomization (SOC results within 7 days prior to transplant may be used), and must also agree to use a medically approved method of contraception. Acceptable methods include: barrier method, intrauterine device (hormonal or non-hormonal), oral hormonal contraceptives, abstinence from the time of enrollment through until discontinuation of ganciclovir or valganciclovir in either arm during the intervention period. NOTE: Individuals of reproductive potential are defined as individuals who have reached menarche and who have not been post-menopausal for at least 12 consecutive months with follicle stimulating hormone (FSH) ≥40 IU/mL or 24 consecutive months if an FSH is not available, i.e., who have had menses within the preceding 24 months, and have not undergone a sterilization procedure (e.g., hysterectomy, bilateral oophorectomy, or salpingectomy). 6. If male, must agree to practice a barrier method of contraception or abstinence from the time of enrollment through 3 months after discontinuation of ganciclovir or valganciclovir in either arm during the intervention period. Exclusion Criteria: 1. In the opinion of the investigator, participants who are unable or unwilling to undergo preemptive therapy protocol (weekly CMV PCR, etc.) 2. Patients who are breastfeeding or planning to breastfeed within 6 months post-transplant 3. Allergy to valganciclovir/ganciclovir or Letermovir 4. Receipt of immunoglobulin or CMV-specific immunoglobulin within the last 3 months (this includes COVID convalescent plasma) 5. Currently enrolled or anticipated enrollment in another interventional study that, in the opinion of scientific leadership team, could affect evaluation of the primary safety and/or efficacy outcomes. 6. Most recent platelet count post-transplant \<25,000/uL 7. Most recent ANC performed post-transplant \<1000/uL 8. Multi-organ transplant (except simultaneous kidney-pancreas) within the past 7 days 9. Prior or planned receipt of a hematopoietic cell transplant 10. Baseline immunodeficiency prior to transplant, including but not limited to: 1. Known or suspected HIV infection 2. Congenital or acquired immunodeficiency 11. Unacceptable immunosuppression 1. Receipt of desensitization therapy prior to kidney transplant, or 2. Receipt of an ABO-incompatible kidney transplant except A2 to blood type B