Incidence of cytomegalovirus UL97 and UL54 amino acid substitutions detected after 100 or 200 days of valganciclovir prophylaxis
ABSTRACT The IMPACT study was a randomized, double-blind study comparing 100 to 200 days of VGCV prophylaxis (900 mg once daily) in D+/R- kidney transplant recipients. Although extending the duration of prophylaxis resulted in a significant reduction in confirmed cytomegalovirus (CMV) disease (100-day: 36.8% vs 200-day: 16.1%(1)), the consequence of extending the duration of prophylaxis on the development of viral resistance remains unknown.
To determine whether extending valganciclovir prophylaxis from 100 days to 200 days increased the incidence of ganciclovir resistance.
Genotypic analysis of CMV UL97 and UL54 was conducted on virus isolated from patients meeting the predefined resistance analysis criteria (RAC).
A greater number of patients met the RAC in the 100 day prophylaxis arm (50/163; 31%) compared to the 200 day prophylaxis arm (22/155; 14%). Sequence data were successfully generated for all 200-day patients and 48/50 100-day patients. Three patients in each treatment arm (100 day: 3/163 (1.8%) vs 200 day: 3/155 (1.9%)) had a single known valganciclovir resistance mutation detected (100 day: UL97 gene: M460V, C592G twice; 200 day: UL97 gene: C603W, M460V and UL54 gene: P522S). Overall, a resistance mutation was more likely to be detected if the patient met the RAC during prophylaxis (5/12 (42%)) compared to post-prophylaxis (1/58 (2%)). All six patients with known ganciclovir resistance mutations cleared the virus; three cleared virus without treatment and three cleared virus following treatment.
Extending valganciclovir prophylaxis from 100 days to 200 days did not significantly affect the incidence of ganciclovir resistance.
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- "There were no significant differences among patients getting antiviral prophylaxis versus pre-emptive therapy in preventing CMV disease , however, long-term graft survival was higher with antiviral prophylaxis . Drug resistant CMV has been observed in patients receiving antiviral prophylaxis or preemptive therapy [69-73]. The incidence of CMV drug resistance in D+/R- kidney recipients was similar if they received 100 days or 200 days of valganciclovir prophylaxis (1.8 and 1.9%, respectively) . "
ABSTRACT: Cytomegalovirus (CMV) continues to have a tremendous impact in solid organ transplantation despite remarkable advances in its diagnosis, prevention and treatment. It can affect allograft function and increase patient morbidity and mortality through a number of direct and indirect effects. Patients may develop asymptomatic viremia, CMV syndrome or tissue-invasive disease. Late-onset CMV disease continues to be a major problem in high-risk patients after completion of antiviral prophylaxis. Emerging data suggests that immunologic monitoring may be useful in predicting the risk of late onset CMV disease. There is now increasing interest in the development of an effective vaccine for prevention. Novel antiviral drugs with unique mechanisms of action and lesser toxicity are being developed. Viral load quantification is now undergoing standardization, and this will permit the generation of clinically relevant viral thresholds for the management of patients. This article provides a brief overview of the contemporary epidemiology, clinical presentation, diagnosis, prevention and treatment of CMV infection in solid organ transplant recipients.09/2013; 45(3):260-271. DOI:10.3947/ic.2013.45.3.260
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ABSTRACT: Cytomegalovirus (CMV) remains one of the most common infections after solid organ transplantation, resulting in significant morbidity, graft loss, and occasional mortality. Management of CMV varies considerably among transplant centers. A panel of experts on CMV and solid organ transplant was convened by The Infectious Diseases Section of The Transplantation Society to develop evidence and expert opinion-based consensus guidelines on CMV management including diagnostics, immunology, prevention, treatment, drug resistance, and pediatric issues.Transplantation 03/2010; 89(7):779-95. DOI:10.1097/TP.0b013e3181cee42f · 3.78 Impact Factor
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ABSTRACT: Cytomegalovirus (CMV) is one of the most important pathogens that infect solid organ transplant recipients. CMV is associated with increased morbidity and mortality in this population as a result of its numerous direct and indirect effects. Prevention strategies consist of preemptive therapy and antiviral prophylaxis, and the choice of which preventive approach to implement should be guided by advantages and drawbacks related to the population being managed. There are differences in the approaches to the laboratory diagnosis and treatment of CMV infection and disease depending on assay availability, clinical presentation, disease severity, and specific transplant populations. In this article, the authors aim to summarize recent publications and updates in the epidemiology, diagnosis, prevention, and treatment of CMV infection in solid organ transplant recipients during the past year, including a brief review of future directions in the field.Current Infectious Disease Reports 09/2012; 14(6). DOI:10.1007/s11908-012-0292-2