Background and Importance Cytomegalovirus (CMV) is one of the most common pathogens in immunocompromised patients. Patients who develop severe CMV infection should be treated with antiviral agents until symptoms are resolved and plasma CMV load is controlled. Management of these patients is sometimes difficult due to resistance or ineffectiveness.
Aim and Objectives To describe the response to combined treatment with letermovir, ganciclovir and anti-CMV immunoglobulins (Ig) for CMV infection in an immunocompromised patient refractory to monotherapy treatments.
Material and Methods We describe the case of a 72-year-old male diagnosed with Good’s syndrome (thymoma-associated immunodeficiency), who developed enterocolitis and systemic infection by CMV. Initially, treatment with IV ganciclovir produced clinical and virological response, but later relapse occurred and resistance to ganciclovir was detected. IV Foscarnet was initiated, obtaining response. After switching to oral letermovir (secondary prophylaxis) having low plasma CMV levels, the patient showed virological failure and foscarnet therapy was reinitiated. After a transient response, foscarnet proved to be insufficient (alone or in combination with ganciclovir) to stop a progressive rise in CMV plasma levels. To control CMV and facilitate intravenous to oral switch, combined treatment with oral letermovir and IV ganciclovir was proposed, added to anti-CMV Ig that the patient was already receiving monthly since the onset of CMV infection.
Effectiveness of this triple therapy was assessed by reduction of CMV plasma load.
Results When absence of letermovir resistance was confirmed, combined off-label use of letermovir, ganciclovir and anti-CMV Ig was approved. The authorisation was based on the absence of therapeutic alternatives and the support of several cases reflecting the good results of this triple therapy.
Despite an initial peak in CMV viral load, triple therapy exhibited a good virological response (CMV <1000 copies/ml) and tolerance. No renal or bone marrow toxicity was detected. IV Ganciclovir was later replaced by valganciclovir for home treatment, maintaining low levels of CMV <300 copies/ml.
Conclusion and Relevance This is the first case of letermovir-ganciclovir-antiCMV Ig combined therapy in a patient with acquired immune deficiency. Previously, it was used in a small cohort of transplant patients. Therefore, this triple therapy should be considered as a possible therapeutic alternative for refractory CMV infection, even if resistant to ganciclovir.
Conflict of Interest No conflict of interest
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