Abstract
BackgroundSeveral anti-viral drugs have demonstrated efficacy in preventing Cytomegalovirus (CMV) infections in solid organ transplant (SOT) patients. The recently approved valganciclovir is the most commonly used and most expensive drug for CMV prevention. The safety and efficacy data have been drawn from a single trial. We hypothesized that valganciclovir may not be as safe as nor more effective than other therapies for CMV prevention.MethodsAll experimental and analytical studies that compared valganciclovir with other therapies for prevention of CMV infection after SOT were selected. Based on meta-analytic and multivariate regression methodologies we critically analyzed all available evidence.FindingsNine studies were included (N = 1,831). In trials comparing valganciclovir with ganciclovir, the risk for CMV disease is 0.98 (95% Confidence Interval (95%CI) 0.67 to 1.43; P = 0.92; I2 = 0%). Valganciclovir was significantly associated with the risk of absolute neutropenia (<1,500/mm3) compared with all therapies (Odds Ratio (OR) 3.63 95%CI 1.75 to 7.53; P = 0.001; I2 = 0%); with ganciclovir only (OR 2.88, 95%CI 1.27 to 6.53; P = 0.01; I2 = 0%); or with non-ganciclovir therapies (OR 8.30, 95%CI 1.51 to 45.58; P = 0.01; I2 = 10%). For a neutropenia cut-off of <1,000/mm3, the risk remained elevated (OR 1.97, 95%CI 1.03 to 3.67; P = 0.04; I2 = 0%). For every 24 patients who receive valganciclovir prophylaxis, one more will develop neutropenia compared to other therapies. The risk of late-onset CMV disease with valganciclovir was similar to ganciclovir and higher than those with non-ganciclovir therapies (OR 8.95, 95%CI 1.07 to 74.83; P = 0.04; I2 = 0%]. One more patient will develop late-onset CMV disease for every 25 who receive valganciclovir compared to treatment with non-ganciclovir therapies. The risk of CMV tissue-invasive disease in liver recipients receiving valganciclovir was 4.5 times the risk seen with ganciclovir [95%CI 1.00 to 20.14] (p = 0.04). All results remained consistent across different study designs, valganciclovir doses, and CMV serostatus.ConclusionsValganciclovir shows no superior efficacy and significantly higher risk of absolute neutropenia, CMV late-onset disease, and CMV tissue-invasive disease compared to other standard therapies. Due to the availability of efficacious, safer, and lower cost drugs (high-dose acyclovir, valacyclovir, ganciclovir), our results do not favor the use of valganciclovir as a first-line agent for CMV preemptive or universal prophylaxis in SOT patients.
Highlights
Cytomegalovirus (CMV) is the most frequent opportunistic infection in solid organ transplant (SOT) patients, causing either CMV syndrome or CMV disease usually in the first year post-transplant [1,2]
Valganciclovir shows no superior efficacy and significantly higher risk of absolute neutropenia, CMV late-onset disease, and CMV tissue-invasive disease compared to other standard therapies
Due to the availability of efficacious, safer, and lower cost drugs, our results do not favor the use of valganciclovir as a first-line agent for CMV preemptive or universal prophylaxis in SOT patients
Summary
Cytomegalovirus (CMV) is the most frequent opportunistic infection in solid organ transplant (SOT) patients, causing either CMV syndrome (fever, malaise and cytopenia) or CMV disease usually in the first year post-transplant [1,2]. Several approaches have evolved to prevent this infection, including universal prophylaxis with anti-viral agents (i.e. acyclovir, valacyclovir, ganciclovir, valganciclovir), and pre-emptive strategy with ganciclovir or valganciclovir. Valganciclovir is the most widely employed drug for pre-emptive and universal prophylaxis, used in approximately two-thirds of all SOT patients [5,6]. The reasons for this popularity are multifactorial, including the convenience of once daily dosing, limitations on the production of oral ganciclovir, and influential marketing strategies by the manufacturer. Several anti-viral drugs have demonstrated efficacy in preventing Cytomegalovirus (CMV) infections in solid organ transplant (SOT) patients. We hypothesized that valganciclovir may not be as safe as nor more effective than other therapies for CMV prevention
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