Prophylaxis Durations and Risks of Cytomegalovirus Infection and Disease in Solid Organ Transplant Recipients: An International, Multicenter Cohort Study

BACKGROUND: The optimal duration of cytomegalovirus (CMV) prophylaxis in solid organ transplant recipients (SOTr) remains undetermined. We evaluated real-life preventive strategies on the incidence of CMV disease in an international SOTr cohort. METHODS: All CMV IgG donor (D)+/recipient (R)- or R+ SOTr in Zürich, Lausanne, and Copenhagen (2008-2022) were followed 12-month post-transplantation. Multivariable Poisson regression examined associations between antiviral prophylaxis duration and risk of CMV infection and CMV disease at time of infection diagnosis. RESULTS: We included 3203 non-lung (2057 kidney, 815 liver, 331 heart) and 620 lung transplant recipients. Strategies for CMV prophylaxis durations varied from none to ≥ 12 months. For D+/R- non-lung SOTr, no prophylaxis with preemptive therapy only versus 3 months of prophylaxis was associated with higher risk of CMV infection and disease (adjusted incidence rate ratio [aIRR] [95% CI] 2.46 [1.69-3.57], and 2.82 [1.18-6.68]). Risk did not differ between 3 and 6 months of prophylaxis. For D+/R- lung transplant recipients, 3 versus 6 months of prophylaxis was associated with higher risk of CMV infection and high CMV DNAemia (2.74 [1.36-5.52] and 8.10 [1.89-41.90]), but not significantly higher risk of CMV disease. Irrespective of antiviral prophylaxis duration, incidence of CMV disease was lower among R+ compared to D+/R- SOTr. CONCLUSIONS: In a setting with CMV surveillance after prophylaxis, 3 months of antiviral prophylaxis seems adequate to prevent CMV disease in D+/R- non-lung SOTr, whereas lung transplant recipients may benefit from longer duration of prophylaxis. Risk of CMV disease was low among R+ SOTr, irrespective of antiviral prophylaxis.