Is preemptive therapy (based on the initiation of antiviral therapy for early asymptomatic cytomegalovirus [CMV] viremia detected by surveillance testing) more effective than antiviral prophylaxis (administered to all patients for 100 days) for the prevention of CMV disease in CMV-seronegative liver transplant recipients with seropositive donors?
In this randomized clinical trial that included 205 CMV-seronegative liver transplant recipients with seropositive donors, the use of antiviral preemptive therapy with valganciclovir, 900 mg twice daily, compared with antiviral prophylaxis with valganciclovir, 900 mg once daily, resulted in CMV disease incidence over 12 months of 9% vs 19%, a difference that was statistically significant.
The use of preemptive therapy, compared with antiviral prophylaxis, reduced the 12-month incidence of CMV disease.
Despite the use of a cytomegalovirus (CMV) prevention strategy of antiviral prophylaxis for high-risk CMV-seronegative liver transplant recipients with seropositive donors, high rates of delayed-onset postprophylaxis CMV disease occur. An alternate approach, preemptive therapy (initiation of antiviral therapy for early asymptomatic CMV viremia detected by surveillance testing), has not previously been directly compared with antiviral prophylaxis in these patients.
To compare preemptive therapy with antiviral prophylaxis in CMV-seronegative liver transplant recipients with seropositive donors for the prevention of CMV disease.
Design, Setting, and Participants
Randomized clinical trial of preemptive therapy vs antiviral prophylaxis in 205 CMV-seronegative liver transplant recipients with seropositive donors aged older than 18 years. The trial was conducted at 6 academic transplant centers in the United States between October 2012 and June 2017, with last follow-up in June 2018.
Patients were randomized 1:1 to receive either preemptive therapy (valganciclovir, 900 mg, twice daily until 2 consecutive negative tests a week apart) for viremia detected by weekly plasma CMV polymerase chain reaction for 100 days (n = 100) or valganciclovir, 900 mg, daily for 100 days as antiviral prophylaxis (n = 105).
Main Outcomes and Measures
The primary outcome was incidence of CMV disease by 12 months, defined as CMV syndrome (CMV viremia and clinical or laboratory findings) or end-organ disease. Secondary outcomes included acute allograft rejection, opportunistic infections, graft and patient survival, and neutropenia.
Among 205 patients who were randomized (mean age, 55 years; 62 women [30%]), all 205 (100%) completed the trial. The incidence of CMV disease was significantly lower with preemptive therapy than antiviral prophylaxis (9% [9/100] vs 19% [20/105]; difference, 10% [95% CI, 0.5% to 19.6%]; P = .04]). The incidence of allograft rejection (28% vs 25%; difference, 3% [95% CI, −9% to 15%]), opportunistic infections (25% vs 27%; difference, 2% [95% CI, −14% to 10%]), graft loss (2% vs 2%; difference, <1% [95% CI, −4% to 4%]), and neutropenia (13% vs 10%; difference, 3% [95% CI, −5% to 12%]) did not differ significantly for the preemptive therapy vs antiviral prophylaxis group, respectively. All-cause mortality at last follow-up was 15% in the preemptive therapy vs 19% in the antiviral prophylaxis group (difference, 4% [95% CI, −14% to 6%]; P = .46).
Conclusions and Relevance
Among CMV-seronegative liver transplant recipients with seropositive donors, the use of preemptive therapy, compared with antiviral prophylaxis, resulted in a lower incidence of CMV disease over 12 months. Further research is needed to replicate these findings and assess long-term outcomes.
ClinicalTrials.gov Identifier: NCT01552369
Singh N, Winston DJ, Razonable RR, et al. Effect of Preemptive Therapy vs Antiviral Prophylaxis on Cytomegalovirus Disease in Seronegative Liver Transplant Recipients With Seropositive Donors: A Randomized Clinical Trial. JAMA. 2020;323(14):1378–1387. doi:10.1001/jama.2020.3138
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