Letermovir Treatment for Refractory or Resistant Cytomegalovirus Infection

Inclusion Criteria: * Age ≥12 years * Weight ≥30 kg * Transplant recipient (HCT, SOT) or other immunocompromised patients including those with HIV infection that require antiviral treatment for CMV. * Documented CMV disease or persistent CMV infection (CMV virus load above 500 IU/mL on consecutive measurements, at least one day apart). * CMV infection is refractory to treatment (defined as ≥14 days of standard CMV treatment without clinical improvement for CMV disease, or failure to achieve \>1 log reduction in CMV VL after ≥14 days of standard treatment for CMV infection)16,17 * Current CMV infection has documented genotypic resistance to ganciclovir or foscarnet. * For patients with any prior CMV infection episode that broke through letermovir prophylaxis, but not during the current CMV infection, documentation of letermovir susceptibility testing should demonstrate absence of letermovir mutations known to confer resistance to letermovir. * Severe myelosuppression (ANC \<1000/µL, Hemoglobin \<8g/dL, or Platelets \<25,000/µL)17 or renal dysfunction (estimated creatinine clearance \<60 mL/min by MDRD in adults or \< 60 ml/min/1.73 m2 by bedside Schwartz equation in \< 18 years-old) at baseline or which develops during antiviral treatment. --Patients who develop severe myelosuppression or renal dysfunction during antiviral treatment as defined above are eligible without having to meet the refractoriness/antiviral resistance criterion. * Combinations of genotypic antiviral resistance and organ dysfunction that lead to eligibility are presented in the full protocol eligibility table. * The effects of letermovir on the developing human fetus are unknown. For this reason, women of child-bearing potential and men must agree to use adequate contraception (barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and 3 months after completion of letermovir administration. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 3 months after completion of letermovir administration. --Patients of childbearing potential must have a negative serum or urine pregnancy test. * Able to understand and the willingness to sign a written informed consent document. Exclusion Criteria: * History of allergic reactions attributed to compounds of similar chemical or biologic composition to letermovir. * Known history of cirrhosis with Child-Pugh Class C hepatic insufficiency at screening. * Acute liver injury at baseline meeting Hy's law. * Current CMV infection broke through letermovir prophylaxis. * Patients with life expectancy of less than a week. Determination of life expectancy will be discussed with the patient's primary treatment physician. * Patient taking strong inhibitors or inducers of hepatic CYP enzymes including rifampicin, phenytoin, clarithromycin, ritonavir, or cobicistat. * HIV patients who are receiving antiretroviral treatment protease inhibitors (darunavir, lopinavir, etc) whether by themselves or boosted with ritonavir or cobicistat, or HIV patients receiving cyclosporine treatment due to strong drug-drug interactions. * Combinations of genotypic antiviral resistance and organ dysfunction that do not meet eligibility criteria are described in the full protocol eligibility table.