Inclusion Criteria:  Adults between 18-70 will be eligible for participation Written informed consent and able to participate with follow up Heart transplant recipients who are not CMV donor negative and CMV recipient negative (CMV -/-) Not enrolled in competing clinical trials  Exclusion Criteria:  Dual heart and kidney transplant recipients Patients who do not survive 72 hours post transplant HIV infection Patients with creatinine clearance less than 10 ml per min at time of enrollment Hypersensitivity to letermovir On CVVH or renal dialysis at the time of enrollment Received a previous solid organ transplant or HSCT. Has Child Pugh Class C severe hepatic insufficiency at screening.  Has both moderate hepatic insufficiency AND moderate to severe renal insufficiency at screening.  Note: Moderate hepatic insufficiency is defined as Child Pugh Class B; moderate to severe renal insufficiency is defined as CrCl <50 mL/min, as calculated by the Cockcroft-Gault equation (as above), respectively.  Has a history of malignancy ≤5 years prior to signing informed consent except for adequately treated basal cell or squamous cell skin cancer or in situ cervical cancer or carcinoma in situ; or is under evaluation for other active or suspected malignancy. Is pregnant or expecting to conceive, is breastfeeding, or plans to breastfeed from the time of consent through at least 90 days following cessation of study therapy. Is expecting to donate eggs or sperm starting from the time of consent through at least 90 days following cessation of study therapy. Has a history or current evidence of any condition, therapy, lab abnormality, or other circumstance that might confound the results of the study, interfere with the participant's participation for the full duration of the study, or put the participant at undue risk, as judged by the investigator, such that it is not in the best interest of the participant to participate in this study.  Has exclusionary laboratory value at screening, as listed in Table 1. Table 1 Laboratory Exclusion Criteria Laboratory Assessment Exclusionary Value  Hemoglobin <8 g/dL Platelets <25,000 cells/µL Absolute neutrophil count <1,000 cells/µL Total bilirubin >2.5 × ULN ALT >5 × ULN AST >5 × ULN ALT = alanine aminotransferase; AST = aspartate aminotransferase; CMV = cytomegalovirus; IgG = immunoglobulin G; ULN = upper limit of normal  Is currently participating or has participated in a study with an unapproved investigational compound or device within 28 days, or 5× half-life of the investigational compound (excluding monoclonal antibodies), whichever is longer, of initial dosing on this study. Participants previously treated with an investigational monoclonal antibody will be eligible to participate after a 150-day washout period.  Note: Investigational regimens involving combinations of approved agents are not permitted. Other non-interventional or other observational studies are allowed.  Has previously participated in this study or any other study involving LET.  Has previously participated or is currently participating in any study involving administration of a CMV vaccine or another CMV investigational agent, or is planning to participate in a study of a CMV vaccine or another CMV investigational agent during the course of this study.  -