Antiviral drugs for cytomegalovirus in transplant recipients: advantages of preemptive therapy

Abstract

Currently available, potent antiviral agents have proven highly effective for the prevention of CMV disease during the time that prophylaxis is employed. However, late-onset CMV disease, occurring in 5-18% of the patients, has emerged as a significant complication in organ transplant recipients receiving prophylaxis. Complete suppression of the virus with long-term use of a potent antiviral agent may be less conducive to antigen-induced priming of host responses, which may explain why there is a greater likelihood of late-onset CMV disease. On the other hand, allowing controlled low-level viral replication, implicit in the strategy of preemptive therapy, may facilitate CMV-specific immune reconstitution and have a mitigating effect on the risk of late-onset CMV disease. Preemptive therapy with valganciclovir appears less likely to be associated with CMV disease, largely due to a lower incidence of late-onset CMV disease. Emerging data, documenting that CMV disease in the era of prophylaxis with potent antiviral agents is an independent contributor to mortality, particularly infection-associated mortality, stands to challenge the notion that prophylaxis is more likely to have a beneficial effect on CMV-related secondary outcomes. Preemptive therapy is a more logical and theoretically more appealing approach for the prevention of CMV disease in transplant recipients.

Valacyclovir Prophylaxis Versus Preemptive Valganciclovir Therapy to Prevent Cytomegalovirus Disease After Renal Transplantation

“…Two approaches for CMV disease prevention are currently considered acceptable: universal prophylaxis and preemptive therapy (1,13). Prophylaxis is associated with the risk of late-onset CMV disease and ganciclovir resistance (13,14).…”

Evaluation of intervention strategy based on CMV-specific immune responses after allogeneic SCT

“…[1][2][3][4][5][6] Since therapy of established disease is often inadequate, two strategies have been developed to prevent disease, universal prophylaxis and pre-emptive therapy. Universal prophylaxis is aimed at treating all patients at risk of disease on the basis of pre-transplant factors, whereas in pre-emptive therapy antiviral treatment is limited to patients with laboratory evidence of viral replication.…”

What is the optimal dosage of valganciclovir as preemptive therapy for CMV infection in allogeneic hematopoietic SCT?

“…Valganciclovir hydrochloride (VGC) is an orally available prodrug of ganciclovir (GCV; L-Valyl ester), that was first approved for the prevention of CMV disease in high-risk (donor positive, recipient negative) solid organ transplants (1800 mg/day as a standard dose) and for the treatment of CMV retinitis in HIV positive patients. 1 We read with interest the paper by Ayala et al 2 about the safety and efficacy of VGC preemptive therapy for CMV infection in allogeneic HSCT. However, the optimal dosage of the drug in this setting has not been established yet.…”