Prevention of cytomegalovirus (CMV) has been a critical development in the field of kidney transplant, saving numerous lives. [1,2] Despite valganciclovir (valG), having breakthrough infections, dose-limiting side effects, and a black box warning of teratogenicity, it remains the primary CMV prophylaxis to prevent poor graft and patient outcomes [3,4].

ValA has been demonstrated to reduce the incidence and delay the onset of CMV disease in CMV seronegative (P < 0.001) and seropositive participants (P = 0.03) with few adverse events even when dosed four times daily (8 g/day). It was also more recently demonstrated to be an effective CMV prophylaxis in adult kidney recipients on steroid inclusive immunosuppression with less cost [5,6]. Since adherence is inversely proportional to the number of medication doses per day, we considered four times daily antiviral prophylaxis impractical. But less frequently dosed valA has not been tested for effectiveness in the prevention of CMV. Additionallyand the effectiveness of valA as CMV prophylaxis in higher risk recipients (pediatric recipients and CMV seronegative recipients with seropositive donors) is unknown. Based on our previous work, we considered twice daily valacyclovir to be reasonable as prophylaxis since acyclovir levels were maintained even at 12 h after the dose for prevention [7].

In this phase 2, randomized, open label, valG-controlled, clinical trial, we sought to confirm the safety and efficacy of twice daily valA for CMV prophylaxis after transplantation in adult and pediatric kidney transplant recipients. A secondary endpoint was the effect of valA or valG on the incidence of EBV viremia or EBV disease.