Use of ganciclovir for cytomegalovirus infection

Ganciclovir (9-(1,3-dihydroxy-2-propoxymethyl) guanine, DHPG) is an acyclovir analog with excellent antiviral activity against human cytomegalovirus (CMV). Clinically, CMV infection occurs in from 60 to 90% of all renal transplant recipients and it is responsible for significant patient morbidity and graft loss. The likelihood of infection is closely related to the CMV status of both donor and recipient, with the greatest risk arising in the combination of a seronegative patient receiving a seropositive organ. Intracellularly, DHPG is converted to DHPG-triphosphate, which competitively inhibits DNA polymerase. This conversion is accelerated up to 10-fold in virally infected cells, providing some selectivity of action. Uncontrolled studies demonstrated DHPG efficacy in CMV disease, but experience in children remains limited. Although bone marrow suppression is a major immediate toxicity, long-term concerns about carcinogenesis and infertility mandate careful patient selection. Recently at the University of Minnesota, 93 solid organ recipients (45 renal transplants) including some children have been treated for tissue-invasive CMV with DHPG. All had a characteristic clinical picture and either a positive CMV culture or a biopsy with CMV inclusions. The patients received i.v. DHPG (10 mg/kg/day) with appropriate adjustments for renal function. In renal allograft recipients, 89% recovered within 30 days, although 21% had to be retreated with DHPG. Although no patient died, allograft survival was significantly reduced (P = 0.02). An additional subgroup of patients (N = 18) who had both biopsy-proven rejection and invasive CMV disease were simultaneously treated for both processes. All of these patients recovered from their CMV infection, but two grafts were lost to rejection. Initial results with DHPG are encouraging and should prompt aggressive efforts toward the early diagnosis of CMV disease, so that appropriate therapy may begin.