Cytomegalovirus Infections, Solid Organ Transplantation, Solid Organ Transplantation Recipient
Conditions
Keywords
CMV, refractory infection, antiviral resistance, solid organ transplant, Drug Resistance, Viral
Brief summary
This study will describe the frequency and characteristics of refractory and resistant cytomegalovirus (CMV) infection in adults who received a solid organ transplant in Argentina between 2017 and 2024. Researchers will review medical records from transplant centers across the country to identify episodes of CMV infection that did not respond adequately to standard antiviral treatment (refractory) or that showed genetic mutations associated with drug resistance. The study will describe the clinical features, treatments used, and outcomes (including graft function and survival) of patients with these episodes, in order to better understand how common this problem is and what factors are associated with it in the local population.
Detailed description
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.
Interventions
None listed
Sponsors
Hospital Italiano de Buenos Aires
Takeda Pharmaceuticals North America, Inc.
Study design
Observational model
COHORT
Time perspective
RETROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Adult patients (≥18 years) who received a solid organ transplant (kidney, liver, heart, lung, pancreas, or combined) at a participating center in Argentina between January 1, 2017 and December 31, 2024 * Documented CMV infection within 18 months post-transplant * Followed for at least 18 months from transplant and at least 12 months from CMV infection onset
Exclusion criteria
* Patients with incomplete medical records precluding assessment of CMV infection status or key study variables * Patients not meeting the minimum follow-up period from transplant or from infection onset
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of refractory or resistant CMV infection | Within 18 months post-transplant, assessed retrospectively for the period January 2017 to December 2024 | Proportion of solid organ transplant recipients with CMV infection who meet operational criteria for refractory infection (viral load unchanged or increased after 2 weeks of appropriate antiviral treatment) or resistant infection (refractory infection plus documented genetic mutation, e.g. UL97 and/or UL54, associated with antiviral resistance) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of overall CMV infection | Within 18 months post-transplant, 2017-2024 | Proportion of SOT recipients with any CMV infection (primary infection, reactivation, asymptomatic infection, or disease), stratified by transplanted organ |
| Distribution of clinical forms of CMV infection | Within 18 months post-transplant, 2017-2024 | Classification of CMV episodes as primary infection, reactivation, asymptomatic infection, or CMV disease |
| Frequency of antiviral resistance mutations | From T3 (declaration of refractoriness) to T4 (episode resolution), up to 12 months | Proportion of genotyped refractory CMV episodes with ≥1 resistance-associated mutation (UL97 and/or UL54) |
| Antiviral treatment lines and combination therapy use | From T2 (treatment initiation) to T4 (negativization) or last available PCR if not resolved, up to 12 months | Number of antiviral treatment lines used per episode (1, 2, ≥3) and proportion of episodes receiving combination antiviral therapy (≥2 active agents ≥72h) |
| All-cause mortality | 90 days and 1 year post-episode onset | Proportion of patients who died at 90 days and at 1 year after the CMV refractory/resistant episode |
| Graft outcome | rejection following the CMV refractory/resistant episode Through 1 year post-episode onset | Proportion of patients with graft loss or rejection following the CMV refractory/resistant episode |
| Association between mutation type and antiviral treatment received | From T2 (antiviral treatment initiation) to T4 (episode resolution), up to 12 months | Distribution of antiviral treatment regimens received (ganciclovir, foscarnet, letermovir, maribavir, cidofovir, combination therapy) according to mutation type detected (UL97 vs. UL54 vs. none) |
| Virologic response | From T2 (treatment initiation) to T4 (confirmed negativization), up to 12 months, with censoring at last available PCR for patients not achieving negativization | Time to virologic negativization (two consecutive negative PCR results ≥7 days apart) |
Countries
Argentina
Contacts
CONTACTLaura Alicia Barcan, MD
CONTACTEmilio Felipe Huaier Arriazu, MD
Outcome results
None listed