-
Liver Transplantation : Official... Dec 2012Valganciclovir (VGC) was approved by the Food and Drug Administration in 2004 as cytomegalovirus (CMV) prophylaxis except for liver transplant recipients because of... (Meta-Analysis)
Meta-Analysis Review
Valganciclovir (VGC) was approved by the Food and Drug Administration in 2004 as cytomegalovirus (CMV) prophylaxis except for liver transplant recipients because of their high incidence of CMV disease with this drug. However, surveys have shown its common off-label use for CMV prophylaxis in liver transplant recipients. We aimed to evaluate the risk of CMV disease with VGC prophylaxis in liver transplant recipients. All studies that evaluated liver transplant recipients and used VGC (900 or 450 mg daily) for the prevention of CMV disease were included. Five controlled studies (n = 483) were pooled with a random effects model; five single-arm studies (n = 380) were pooled for the prevalence rate of CMV disease. The risk of CMV disease with VGC versus ganciclovir was 1.81 [95% confidence interval (CI) = 1.00-3.29, P = 0.05, I(2) = 0%]. For high-risk (donor-positive/recipient-negative) patients, the risk of CMV disease was 1.96 (95% CI = 1.05-3.67, P = 0.035, I(2) = 0%). The risk of CMV disease remained significant with 900 mg of VGC daily (P = 0.04) but not with 450 mg of VGC daily (P = 0.76). The risk of leukopenia with VGC was 1.87 (95% CI = 1.03-3.37, P = 0.04, I(2) = 0%). In single-arm trials, the overall CMV disease rate was 12% (95% CI = 9%-16%, P < 0.001), and the rate for high-risk patients was 20% (95% CI = 10%-38%, P = 0.002). In conclusion, 900 mg of VGC daily may not be safe as CMV prophylaxis in high-risk liver transplant recipients because of the significant 2-fold increase in the risk of CMV disease and the 1.9-fold increase in the risk of leukopenia. Alternative CMV prophylaxis should be used for liver transplant recipients.
Topics: Antiviral Agents; Cytomegalovirus Infections; Drug Administration Schedule; Ganciclovir; Humans; Leukopenia; Liver Transplantation; Middle Aged; Odds Ratio; Risk Assessment; Risk Factors; Time Factors; Treatment Outcome; Valganciclovir
PubMed: 22887929
DOI: 10.1002/lt.23530 -
International Journal of Organ... 2012In kidney transplant (KT) recipients, CMV infection poses significant morbidity and mortality. Both prophylactic and pre-emptive approaches for preventing CMV infection...
BACKGROUND
In kidney transplant (KT) recipients, CMV infection poses significant morbidity and mortality. Both prophylactic and pre-emptive approaches for preventing CMV infection have been utilized.
OBJECTIVE
To compare the effectiveness of routine prophylaxis vs. pre-emptive treatment for preventing CMV disease after KT.
METHODS
We conducted a systematic review and meta-analysis comparing the effectiveness of routine prophylaxis vs. pre-emptive treatment for preventing CMV disease after KT. Combining 4 comprehensive search terms (CMV, renal transplant, prophylaxis, pre-emptive); we searched PubMed, EMBASE, ISI Web of Science, and Cochrane Central Register from inception through January 2011. We also evaluated studies referenced in review articles and abstracts from meetings of major nephrology and transplant societies (2009-2011). Two authors independently extracted data and assessed methodological criteria. The primary outcome was the pooled estimate of the odds ratio (OR) of developing CMV infection. Secondary outcomes included OR of acute rejection, OR of graft loss and OR of death within first year of KT. Comprehensive Meta-analysis V2 software was used for data analysis.
RESULTS
Analysis of 9 randomized controlled trials (991 patients; ganciclovir=5, valganciclovir=4) with CMV infection as an outcome revealed the OR of CMV infection to be 0.34 (95% CI: 0.25-0.46, p=0.008) for the prophylactic vs. the pre-emptive groups. The OR of acute rejection (7 studies; 1358 patients) was 0.52 (95% CI: 0.41-0.67, p=0.001) with prophylactic approach compared to pre-emptive treatment; graft loss (7 studies; OR 0.52 [95% CI: 0.34-1.12, p=0.32] and mortality (6 studies; OR 0.84 [95% CI: 0.62-1.23, p=0.23]) were similar between the two groups.
CONCLUSIONS
Prophylactic approach is superior to pre-emptive approach in preventing CMV infection within the first year of kidney transplant. The risk of developing acute rejection is also lower with prophylactic approach in the first year of transplant but there is no significant difference in graft loss or mortality with either approach.
PubMed: 25013618
DOI: No ID Found -
The Cochrane Database of Systematic... Jul 2009Herpes simplex virus (HSV) is a rare but serious neonatal pathogen. Prior to the availability of antiviral drugs the mortality associated with all but localised neonatal... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Herpes simplex virus (HSV) is a rare but serious neonatal pathogen. Prior to the availability of antiviral drugs the mortality associated with all but localised neonatal infection was high, with 85% of infants with disseminated HSV infection and 50% of infants with encephalitis dying by one year of age. The morbidity in the survivors of multiorgan infection was also high, with up to 50% experiencing long-term neurological sequelae.
OBJECTIVES
To determine the effect of antiviral agents in the treatment of neonatal HSV infections on mortality, progression of disease and neurodevelopmental sequelae at approximately one year. The secondary objective was to assess the effect of antiviral agents on major complications associated with the use of these agents including nephrotoxicity and bone marrow suppression.
SEARCH STRATEGY
Trials were identified by searching the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 4, 2008), MEDLINE (1996 - Nov 2008), EMBASE (1982 - Nov 2008) and reference lists of published trials.
SELECTION CRITERIA
Randomised and quasi-randomised controlled trials of antiviral therapy in infants less than one month of age with virologically proven HSV infection were included.
DATA COLLECTION AND ANALYSIS
Data were extracted and the analyses performed independently by two review authors. Studies were analysed for methodological quality using the criteria of the Cochrane Neonatal Review Group. All data were analysed using RevMan 5.1. When possible, meta-analysis was performed to calculate typical relative risk, typical risk difference, along with their 95% confidence intervals (CI).
MAIN RESULTS
Two eligible studies of a total of 273 infants were included. Both studies were randomized controlled trials. One study treated 63 infants with vidarabine or placebo (Whitley 1980) and the other study treated 210 infants with aciclovir or vidarabine (Whitley 1991).In the study comparing vidarabine with placebo (Whitley 1980), infants with all forms of neonatal HSV disease were included [disseminated disease, central nervous system (CNS) disease alone, and skin, eye and mouth (SEM) disease].There was no significant reduction in the risk of mortality when analyzed as an entire group; however, mortality was significantly reduced when data from infants with CNS disease or disseminated disease were combined. There was no difference in the rate of neurological abnormalities in survivors at one year when analyzed as an entire group or by disease category.There was no difference between aciclovir and vidarabine (Whitley 1991) in preventing mortality from neonatal HSV disease, in preventing disease progression, in reducing the incidence of neurological abnormality at one year, or in the incidence of drug-induced renal or bone marrow toxicity. In infants with SEM disease, there was no significant difference in neurological outcome with aciclovir compared vidarabine treatment. Both drugs were well tolerated in the newborn period.
AUTHORS' CONCLUSIONS
There is insufficient trial evidence to evaluate the effects of antiviral agents with controls or with each other. The rarity of the condition makes effectively powered clinical trials difficult to perform. The efficacy of newer antiviral agents with better bioavailability (e.g. valaciclovir, valganciclovir) for the treatment of neonatal disease needs to be evaluated in randomised trials. The efficacy of oral formulations need to be evaluated as they may be useful for infants with skin, eye or mouth HSV disease or in the treatment of infants with recurrences after the neonatal period.
Topics: Acyclovir; Antiviral Agents; Developmental Disabilities; Disease Progression; Herpes Simplex; Humans; Infant, Newborn; Randomized Controlled Trials as Topic; Vidarabine
PubMed: 19588350
DOI: 10.1002/14651858.CD004206.pub2 -
American Journal of Transplantation :... Oct 2008The precise impact of valganciclovir as preventive therapy for cytomegalovirus (CMV) in solid organ transplant (SOT) recipients is not fully defined. Data from studies... (Review)
Review
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 (
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. Topics: Antiviral Agents; Cytomegalovirus; Cytomegalovirus Infections; Ganciclovir; Humans; Kidney Diseases; Kidney Transplantation; Liver Diseases; Liver Transplantation; Risk; Time Factors; Transplantation Immunology; Treatment Outcome; Valganciclovir; Virology
PubMed: 18828771
DOI: 10.1111/j.1600-6143.2008.02369.x