Background Few studies have directly compared preemptive therapy (PET) and antiviral prophylaxis (AP) for prevention of cytomegalovirus disease in CMV seropositive (R+) orthotopic liver transplant (OLT) recipients. Methods We prospectively assessed CMV disease and clinical outcomes among 160 consecutive R+ OLT recipients who received PET (weekly plasma CMV PCR for 3 months, oral valganciclovir 900 mg twice daily for CMV viremia >250 IU/mL, until 2 consecutive negative weekly PCR results) and compared them to a historical cohort of 156 R+ recipients who received AP (valganciclovir 900 mg daily for 3 months). Results Patient characteristics were similar between PET and AP cohorts (p>0.05 all comparisons). In the PET group, 24% (39/160) developed CMV viremia >250 IU/mL at a median of 42 (range 7-93) days post-OLT. CMV monitoring adherence in the PET cohort was 85% (1488/1760 required tests) and 86% (30/36) initiated PET within 3 days of the CMV result. By 12 months post-OLT, the incidence of CMV disease, acute allograft rejection, major infection, or death in the PET and AP cohorts was not significantly different: 2% vs 2%, 19% vs 16%, 10.5% vs 10.8%, and 5% vs 8%, respectively (p > 0.05 all comparisons). The estimated proportion of drug-exposed patients and average antiviral drug exposure were significantly lower with PET vs AP: 24% vs 100%, p
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