Prophylaxis of Cytomegalovirus Infection in Solid Organ Transplantation, Retrospective Evaluation (original) (raw)
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American Journal of Transplantation, 2010
Data from all CMV D+/R-kidney transplant recipients between January 2004 and December 2008 at our center were analyzed. Patients with a functioning graft at 6 months after transplantation who received 6 months of valganciclovir prophylaxis 900 mg once daily were included (N = 127). CMV was diagnosed with quantitative PCR. Prophylaxis was completed in 119 patients. Prophylaxis was stopped at 3-5 months due to leukopenia or gastrointestinal side effects in eight patients. Late-onset primary CMV infection developed in 47/127 (37%) patients median 244 days after transplantation (range 150-655) and median 67 days after the cessation of prophylaxis (range 1-475). Four infections were asymptomatic. In others, symptoms included fever (N = 28), gastrointestinal symptoms (nausea, vomiting, diarrhea) (N = 24), respiratory tract symptoms (N = 12), and hepatopathy (N = 6). Median peak viral load was 13500 copies/mL (range 400-2 831 000). Recurrent CMV infection developed in 9/47 (19%) patients. No significant risk factors for CMV infection were identified.
Transplantation Proceedings, 2017
Cytomegalovirus (CMV) is the most common viral infection during the post-transplant period, and it is one of the major causes of morbidity and mortality in kidney transplantation. In this study, the incidence and impact of pre-emptive and prophylactic approaches and long-term effects on graft and patient survival of CMV infection were investigated. Among 493 adult kidney transplant recipients, pretransplant CMV IgGnegative patients and patients with a follow-up shorter than a month were excluded. The patients were divided into 2 groups: pre-emptive group (n ¼ 187, regular screening and acyclovir 400 mg twice daily for 6 months), and prophylaxis group (n ¼ 275, valganciclovir 450 mg/d for 3 months). The pre-emptive group was screened for CMV with either pp65 antigenemia or CMV DNA. There were 462 patients, and mean follow-up was 37.7 months. There were more CMV infections in the pre-emptive group than in the prophylaxis group (n ¼ 56, 30.1% vs n ¼ 12, 4.4%, respectively; P < .001). Late CMV infections were significantly more frequent in the prophylaxis group (10 of 12, 83.3%) than in the pre-emptive group (8 of 56, 14.3%, P < .001). In multivariate analysis, valganciclovir prophylaxis was associated with a lower CMV infection (relative risk [RR]: 0.18, 95% confidence interval [CI] 0.08 to 0.39, P < .001). Delayed graft function was the only independent risk factor for graft loss during the follow-up on multivariate Cox regression analysis (RR: 2.66, 95% GA 1.17 to 6.04, P ¼ .02). Valganciclovir prophylaxis was more protective against CMV infection than the pre-emptive approach. Neither prophylaxis/pre-emptive approaches nor CMV infection had negative effect on graft and patient survival.
Transplantation, 2004
Background. Cytomegalovirus (CMV) Dϩ/RϪ solid-organ transplant (SOT) recipients carry increased risk of developing CMV disease; however, other risk factors in these patients have not been delineated. Methods. We examined 20 demographic and clinical variables for their association with the development of CMV disease, as defined by an independent endpoint committee (IEC) and also by the investigator (investigator treated [IT]), or CMV viremia within 12 months of transplant in Dϩ/RϪ transplant recipients who received prophylaxis with valganciclovir or oral ganciclovir for 100 days. Results. Recipients with low creatinine clearance (C cr ,Ͻ40 mL/min) at screening had a significantly increased hazard of developing IEC-defined CMV disease (hazards ratio [HR]ϭ4.28, confidence interval [CI] 1.69, 10.83). Females were twice as likely (HRϭ2.19, CI .21, 3.99) to develop IEC-defined CMV disease than males. These variables were associated with an increased risk of IEC-defined CMV disease in time-dependent models. Recipients with blood group A were also more likely to develop IEC-defined CMV disease than those with group O (HRϭ2.36 CI 1.24, 4.51) in the logistic regression model only. Prophylactic drug, organ type, recipient age, rejection episodes, and maintenance immunosuppression regimen were not associated with IEC-defined CMV disease. Female sex was the only variable associated with the development of CMV viremia (odds ratio [OR]ϭ1.65; CI 1.03, 2.65) and IT CMV disease (ORϭ1.78; CI 1.08, 2.93). Conclusions. Low C cr at screening and blood type A are risk factors for IEC-defined CMV disease, and female sex was a risk factor for IEC-and IT-defined CMV disease and viremia in high-risk SOT recipients. These variables should perhaps be considered when optimizing treatment.
Comparing cytomegalovirus prophylaxis in renal transplantation: single center experience
Transplant Infectious Disease, 2005
Abstract: Background: Cytomegalovirus (CMV) presents a serious threat to CMV-seronegative recipients (R−), who have received an organ from a seropositive donor (D+).Objectives: We compared the effectiveness of three different prophylactic protocols in CMV D+/R− patients and reviewed data on patients who received no prophylaxis.Patients and methods: We reviewed 1137 kidney transplantations from 1995 to 2004. Of these, 147 recipients were CMV negative (D+/R−); 125 patients received CMV prophylaxis. Group I received CMV hyperimmune gammaglobulin only, group II received CMV hyperimmune gammaglobulin plus oral ganciclovir, and group III received prophylaxis with oral ganciclovir only.Results: In group I, CMV infection was observed in 31 of 53 patients (59%), and CMV disease was diagnosed in 9 (17%) during the prophylaxis. In the first year post transplant, a total of 41 of 53 patients (77.5%) had primary CMV infection. In group II, CMV infection occurred in 7 of 30 patients (23%), and CMV disease was diagnosed in only 2 (7%) during prophylaxis. In the first year post transplant, a total of 9 of 30 patients (30%) had primary CMV infection. In group III, 9 of 42 patients (21%) developed CMV infection during prophylaxis, and CMV disease was not observed. In the first year post transplant, a total of 13 of 42 patients (30%) had primary CMV infection. In contrast, all 22 CMV D+/R− patients without prophylaxis developed CMV infection (100%); CMV disease was diagnosed in 10 (45%), and 1 patient died.Conclusions: Prophylaxis with hyperimmune gammaglobulin and/or oral ganciclovir significantly reduces CMV infection and disease. Prophylaxis with ganciclovir was significantly more effective than hyperimmune gammaglobulin monoprophylaxis, and more cost effective than combined prophylaxis.
Journal of the American Society of Nephrology, 2009
The risk of late-onset cytomegalovirus (CMV) infection remains a concern in seronegative kidney and/or pancreas transplant recipients of seropositive organs despite the use of antiviral prophylaxis. The optimal duration of prophylaxis is unknown. We studied the cost effectiveness of 6-versus 3-mo prophylaxis with valganciclovir. A total of 222 seronegative recipients of seropositive kidney and/or pancreas transplants received valganciclovir prophylaxis for either 3 or 6 mo during two consecutive time periods. We assessed the incidence of CMV infection and disease 12 mo after completion of prophylaxis and performed cost-effectiveness analyses. The overall incidence of CMV infection and disease was 26.7% and 24.4% in the 3-mo group and 20.9% and 12.1% in the 6-mo group, respectively. Six-month prophylaxis was associated with a statistically significant reduction in risk for CMV disease (HR, 0.35; 95% CI, 0.17 to 0.72), but not infection (HR, 0.65; 95% CI, 0.37 to 1.14). Cost-effectiveness analyses showed that 6-mo prophylaxis combined with a one-time viremia determination at the end of the prophylaxis period incurred an incremental cost of 34,362and34,362 and 34,362and16,215 per case of infection and disease avoided, respectively, and $8,304 per one quality adjusted life-year gained. Sensitivity analyses supported the cost effectiveness of 6-mo prophylaxis over a wide range of valganciclovir and hospital costs, as well as variation in the incidence of CMV disease. In summary, 6-mo prophylaxis with valganciclovir combined with a one-time determination of viremia is cost effective in reducing CMV infection and disease in seronegative recipients of seropositive kidney and/or pancreas transplants.
Transplantation reviews (Orlando, Fla.), 2014
Transplant recipients receiving immunosuppressive therapy are at increased risk of active cytomegalovirus (CMV) infection and disease. Without appropriate prophylaxis, as many as 80% of solid organ transplant recipients may experience CMV infection. In addition to the direct effects of CMV, infection may be associated with a range of indirect effects, including an increase in risk of other infections, as well as a higher incidence of rejection, graft loss and death. The indirect effects of CMV infection can vary depending on the transplanted organ. For example, CMV-infected kidney transplant recipients may be at increased risk of cardiovascular disease and diabetes, while CMV infection in liver transplant recipients may potentiate hepatitis C infection and increase the risk of post-transplant lymphoproliferative disease. Indirect effects result from a number of pathological processes, including immune modulation and immunosuppression, generation of cytotoxic, proinflammatory responses, and smooth muscle proliferation. Prophylactic treatment with antiviral medication can reduce the risk of CMV disease, thereby improving graft survival and overall outcomes, particularly in kidney and heart transplant recipients. Antiviral prophylaxis should be considered for all patients at risk of CMV infection after solid organ transplantation. In this paper we review the main indirect effects of CMV infection in solid organ transplant recipients, and the impact of CMV prophylaxis on these effects.
Transplantation Proceedings, 2009
Background. Cytomegalovirus (CMV) disease represents an important cause of morbidity in renal transplant recipients. We report our preliminary evaluation of the efficacy and security of preemptive therapy to manage renal transplant recipients with evidence of active CMV replication. Methods. Preemptive therapy with gancyclovir and/or valgancyclovir (VGCV) was recently substituted for CMV antiviral prophylaxis at our institution. Between May 2006 and December 2007, all patients undergoing renal transplantation were included in a CMV infection surveillance program. Blood samples to determine CMV viral load were obtained weekly during the first 4 months. Asymptomatic patients, with a viral load determined using polymerase chain reaction (PCR) with CMV DNA Ͼ100,000 copies/mL, were treated with VGCV for 3 months or until resolution of viral replication. Until April 2006, patients undergoing renal transplantation received CMV prophylaxis with oral acyclovir and pp65 antigenemia was the test for CMV infection surveillance. The group on preemptive therapy was compared with a historical group on prophylaxis therapy: 100 renal patients who underwent transplantation between April 2004 and 2006. Results. Among 96 recipients, quantitative determination of viral DNA in blood was elevated in 14 asymptomatic patients, who were treated with oral VGCV for 3 months. The patients were followed up for a median time of 13.3 months. None of the 14 patients who received VGCV developed CMV disease. Conclusion. VGCV administered as preemptive therapy was safe and efficacious to prevent CMV disease.
The Brazilian Journal of Infectious Diseases, 2016
Background: The identification of the best strategy to manage cytomegalovirus infection is hampered by uncertainties regarding the risk/benefit ratios of universal prophylaxis versus preemptive therapy, the impact of indirect cytomegalovirus effects and the associated costs. This study investigated the efficacy and safety of targeted preemptive therapy according to perceived risk of cytomegalovirus infection after kidney transplantation. Methods: 144 adult kidney transplant recipients were enrolled in this 12-month study. None received cytomegalovirus pharmacological prophylaxis. Only high risk patients (positive donor/negative recipient (D+/R−), use of induction therapy with antithymocyte globulin, treatment of rejection) received preemptive therapy based on the result of pp65 antigenemia test. Low-risk patients with symptoms related to cytomegalovirus were screened for pp65 antigenemia and treatment initiated if confirmed cytomegalovirus disease. Blinded cytomegalovirus DNAemia was collected weekly during the first three months. Results: The incidence of cytomegalovirus infection was 34% and cytomegalovirus disease was 17%. The incidence was 25% in D+/R−, 69% in those receiving induction with rabbit antithymocite globulin (r-ATG), 46% in those treated for acute rejection, and 28% in low risk patients. By week 3 DNAemia was observed in 30% of patients who were not treated for cytomegalovirus infection/disease, and values ≥2.169 UI/mL showed 61% sensitivity and 85% specificity to detect cytomegalovirus disease (AUC = 0.849 ± 0.042, p < 0.001). Using multivariate analysis, only anti-thymocyte globulin induction was associated with cytomegalovirus infection/disease whereas only expanded donor criteria and renal function at 30 days were associated with renal function 12 months after transplantation.
Journal of Clinical …, 2011
Background: Cytomegalovirus (CMV) remains the leading viral cause of disease following orthotopic liver transplantation (OLT) despite the availability of antiviral agents for prophylaxis and therapy. Objective: Examine the viral factors that influence the outcome of CMV infection following valganciclovir prophylaxis or laboratory-guided preemptive therapy in OLT recipients. Study design: The value of valganciclovir prophylaxis and laboratory-guided preemptive therapy for the prevention of CMV infection and disease was observed in 64 OLT recipients. Prophylaxis was given to all CMV seronegative recipients receiving a liver from a seropositive donor (D+R−; n = 15), and all other recipients were randomised to receive either prophylaxis (n = 24) or laboratory-guided preemptive therapy (n = 25). Recipients were monitored for CMV DNAemia, viral load, emergence of antiviral resistant strains and co-infections. Results: CMV end-organ disease and antiviral resistant strains only occurred in D+R− recipients despite the use of prophylaxis in these patients. The D+R− recipients commencing prophylaxis immediately following transplantation had better outcomes compared to those for whom prophylaxis was delayed due to renal impairment. Prophylaxis reduced the incidence of CMV DNAemia, persistent infection, and high viral loads for CMV seropositive (D−R+and D+R+) recipients, but laboratory-guided preemptive therapy effectively controlled CMV infection and prevented disease in these OLT recipients. Conclusion: Delaying the commencement of valganciclovir prophylaxis may be associated with worse outcomes for high-risk OLT recipients. Laboratory-guided pre-emptive therapy remains an alternative approach for seropositive recipients at lower risk of CMV disease.