Prevention of Posttransplant CMV and Related Outcomes With Valganciclovir
Prevention of Posttransplant CMV and Related Outcomes With Valganciclovir
The precise impact of valganciclovir as preventive therapy for cytomegalovirus (CMV) in solid organ transplant (SOT) recipients is not fully defined. Data from studies using valganciclovir as preemptive therapy or prophylaxis for CMV in SOT recipients were synthesized for descriptive analysis. CMV disease occurred in 2.6% and 9.9% of the patients receiving valganciclovir as preemptive therapy and prophylaxis, respectively. Although the incidence of early-onset (≤90 days posttransplant) CMV disease was only 0.8% and 1.2% in all patients and R-/D+ patients receiving valganciclovir prophylaxis, the incidence of late-onset (>90 days posttransplant) CMV disease rose up to 8.9% and 17.7% in the prophylactic group, respectively. On the contrary, no patients developed late-onset CMV disease in preemptive group. Both approaches with valganciclovir have successfully decreased CMV disease in SOT recipients. Late-onset CMV disease is a complication observed uniquely with valganciclovir prophylaxis, particularly in R-/D+ patients, but not with preemptive therapy.
Cytomegalovirus (CMV) is an important opportunistic pathogen in solid organ transplant (SOT) recipients. In the absence of any form of preventive therapy, CMV infection develops in 36-100% of the SOT recipients and symptomatic disease in 11-72% of the patients, most often during the first 100 days after transplantation. Current antiviral agents and preventive strategies have led to a decrease in the incidence of CMV disease. Compared to patients treated with placebo or no antiviral therapy, those receiving preemptive therapy and prophylaxis have a 72-80% lower likelihood for the development of CMV disease. Furthermore, reduced allograft rejection, opportunistic infections and mortality has been documented with the receipt of prophylaxis.
Despite these advances, a number of issues remain unresolved. Although prophylaxis has effectively prevented CMV disease in the early posttransplant period, the incidence of late-onset CMV disease occurring after discontinuation of prophylaxis has increased from 0-5% in the era of long-term use of acyclovir to 2.6-7% in patient receiving prophylaxis with oral ganciclovir. It has been proposed that the optimal development of long-term protective immunity against CMV may be compromised with the prolonged use of a potent antiviral agent such as ganciclovir. In addition, indirect sequelae of CMV still complicate the posttransplant course.
Valganciclovir has emerged as the preferred antiviral agent for the prevention of CMV in SOT recipients because of its oral availability, convenient dosing schedule, and 10-fold higher bioavailability than oral ganciclovir. Although not approved by the FDA for prophylaxis in liver transplant recipients, surveys of CMV prevention strategies after liver and kidney transplantation show that valganciclovir is the most commonly prescribed antiviral agent for the prevention of CMV. However, existing studies have primarily comprised small sample sizes and previous meta-analyses have excluded valganciclovir. Thus, we performed a review and conducted a systemic analysis to examine the efficacy of valganciclovir as preemptive therapy versus prophylaxis for CMV disease and CMV-associated indirect outcomes in SOT recipients.
The precise impact of valganciclovir as preventive therapy for cytomegalovirus (CMV) in solid organ transplant (SOT) recipients is not fully defined. Data from studies using valganciclovir as preemptive therapy or prophylaxis for CMV in SOT recipients were synthesized for descriptive analysis. CMV disease occurred in 2.6% and 9.9% of the patients receiving valganciclovir as preemptive therapy and prophylaxis, respectively. Although the incidence of early-onset (≤90 days posttransplant) CMV disease was only 0.8% and 1.2% in all patients and R-/D+ patients receiving valganciclovir prophylaxis, the incidence of late-onset (>90 days posttransplant) CMV disease rose up to 8.9% and 17.7% in the prophylactic group, respectively. On the contrary, no patients developed late-onset CMV disease in preemptive group. Both approaches with valganciclovir have successfully decreased CMV disease in SOT recipients. Late-onset CMV disease is a complication observed uniquely with valganciclovir prophylaxis, particularly in R-/D+ patients, but not with preemptive therapy.
Cytomegalovirus (CMV) is an important opportunistic pathogen in solid organ transplant (SOT) recipients. In the absence of any form of preventive therapy, CMV infection develops in 36-100% of the SOT recipients and symptomatic disease in 11-72% of the patients, most often during the first 100 days after transplantation. Current antiviral agents and preventive strategies have led to a decrease in the incidence of CMV disease. Compared to patients treated with placebo or no antiviral therapy, those receiving preemptive therapy and prophylaxis have a 72-80% lower likelihood for the development of CMV disease. Furthermore, reduced allograft rejection, opportunistic infections and mortality has been documented with the receipt of prophylaxis.
Despite these advances, a number of issues remain unresolved. Although prophylaxis has effectively prevented CMV disease in the early posttransplant period, the incidence of late-onset CMV disease occurring after discontinuation of prophylaxis has increased from 0-5% in the era of long-term use of acyclovir to 2.6-7% in patient receiving prophylaxis with oral ganciclovir. It has been proposed that the optimal development of long-term protective immunity against CMV may be compromised with the prolonged use of a potent antiviral agent such as ganciclovir. In addition, indirect sequelae of CMV still complicate the posttransplant course.
Valganciclovir has emerged as the preferred antiviral agent for the prevention of CMV in SOT recipients because of its oral availability, convenient dosing schedule, and 10-fold higher bioavailability than oral ganciclovir. Although not approved by the FDA for prophylaxis in liver transplant recipients, surveys of CMV prevention strategies after liver and kidney transplantation show that valganciclovir is the most commonly prescribed antiviral agent for the prevention of CMV. However, existing studies have primarily comprised small sample sizes and previous meta-analyses have excluded valganciclovir. Thus, we performed a review and conducted a systemic analysis to examine the efficacy of valganciclovir as preemptive therapy versus prophylaxis for CMV disease and CMV-associated indirect outcomes in SOT recipients.
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