Evaluation of Cytomegalovirus Refractoriness and Resistance in Solid Organ Transplantation in Argentina: A Multicenter Study

Cytomegalovirus (CMV) remains one of the most frequent infections after solid organ transplantation (SOT), with important direct and indirect effects on graft and patient survival. While preventive strategies (prophylaxis and preemptive therapy) have reduced CMV-related disease and mortality, refractory and resistant CMV infection continues to be a major challenge, particularly in high-risk transplants (donor-positive/recipient-negative serostatus, and those receiving thymoglobulin induction). No epidemiological data on refractory or resistant CMV currently exist in Argentina.

This multicenter retrospective cohort study will include adult (≥18 years) solid organ transplant recipients from participating centers in Argentina who developed CMV infection within 18 months post-transplant, between January 1, 2017 and December 31, 2024. Cases meeting pre-specified operational criteria for refractory or resistant CMV infection will be identified from medical records. Refractory infection is defined as viral load that does not decrease or increases after two weeks of appropriate antiviral treatment; resistant infection is defined as refractory infection with documentation of at least one genetic mutation (UL97 and/or UL54) associated with antiviral resistance, confirmed through genotyping performed at the national reference laboratory (Instituto Malbrán).

Data will include demographic and transplant-related variables, immunosuppression regimen, virological monitoring, antiviral treatment lines and dosing, resistance genotyping results when available, and clinical outcomes including graft function, rejection episodes, and mortality at 90 days and one year. Data will be collected, coded, and stored in a centralized, de-identified database (REDCap) for descriptive and comparative statistical analysis.