Use of Viral Load as a Surrogate Marker in Clinical Studies of Cytomegalovirus in Solid Organ Transplantation: A Systematic Review and Meta-analysis.
Yoichiro Natori,Ali Alghamdi,Mahmood Tazari,Veronica Miller,Shahid Husain,Takashi E. Komatsu,Paul D. Griffiths,Per Ljungman,Ani Orchanian-Cheff,Deepali Kumar,Atul Humar,Rekha Abichandani,Barbara D. Alexander,Robin K. Avery,Fausto Baldanti,Susan Barnett,Paul Baum,M Michelle Berrey,Debra Birnkrant,Emily A. Blumberg,Michael Boeckh,David Boutolleau,Terry Bowlin,Jennifer Brooks,Roy F. Chemaly,Sunwen Chou,Gavin Cloherty,William Cruikshank,Lesia K. Dropulic,Hermann Einsele,Jay Erdman,Gary Fahle,Lynn Fallon,Heather Gillis,Dimitri Gonzalez,Kurt Gunter,Hans H. Hirsch,Aimee Hodowanec,Peter W. Hunt,Filip Josephson,Camille N. Kotton,Philip R. Krause,Frank Kuhr,Christopher Lademacher,Randall Lanier,Tadd Lazarus,John A. D. Leake,Randi Y. Leavitt,Sandra Nusinoff Lehrman,Li Li,Paula Isabelle Lodding,Jens D Lundgren,Francisco Martinez-Murillo,Howard Mayer,Megan McCutcheon,John E. McKinnon,Thomas Mertens,Kevin Modarress,Johann Mols,Sally Mossman,Yoshihiko Murata,David Murawski,Jeffrey C. Murray,Garrett Nichols,Jules O'Rear,Karl S. Peggs,Andreas Pikis,Mark N. Prichard,Raymund R. Razonable,Marcie L. Riches,Jeff Roberts,Wael Saber,Chalom Sayada,Mary Singer,Thomas Stamminger,Anna Wijatyk,Dong Yu,Bernhardt Zeiher +77 more
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TLDR
It is concluded that CMV load is an appropriate surrogate endpoint for CMV trials in organ transplant recipients due to low frequency of disease and several lines of evidence support the validity of viral load.Abstract:
Symptomatic cytomegalovirus (CMV) disease has been the standard endpoint for clinical trials in organ transplant recipients. Viral load may be a more relevant endpoint due to low frequency of disease. We performed a meta-analysis and systematic review of the literature. We found several lines of evidence to support the validity of viral load as an appropriate surrogate end-point, including the following: (1) viral loads in CMV disease are significantly greater than in asymptomatic viremia (odds ratio, 9.3 95% confidence interval, 4.6-19.3); (2) kinetics of viral replication are strongly associated with progression to disease; (3) pooled incidence of CMV viremia and disease is significantly lower during prophylaxis compared with the full patient follow-up period (viremia incidence: 3.2% vs 34.3%; P < .001) (disease incidence: 1.1% vs 13.0%; P < .001); (4) treatment of viremia prevented disease; and (5) viral load decline correlated with symptom resolution. Based on the analysis, we conclude that CMV load is an appropriate surrogate endpoint for CMV trials in organ transplant recipients.read more
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Cytomegalovirus in solid organ transplant recipients-Guidelines of the American Society of Transplantation Infectious Diseases Community of Practice.
TL;DR: There is an increasing use of CMV‐specific cell‐mediated immune assays to stratify the risk ofCMV infection after solid organ transplantation, but their role in optimizing CMV prevention and treatment efforts has yet to be demonstrated.
Journal ArticleDOI
Pathogenesis of human cytomegalovirus in the immunocompromised host.
TL;DR: A review of immune responses to HCMV and countermeasures deployed by the virus, the establishment of latency and reactivation from it, exogenous reinfection with additional strains, pathogenesis, development of end organ disease, indirect effects of infection, immune correlates of control of replication, current treatment strategies and the evaluation of novel vaccine candidates can be found in this article.
Journal ArticleDOI
Progress and Challenges in the Prevention, Diagnosis, and Management of Cytomegalovirus Infection in Transplantation.
TL;DR: Important developments in the field over the past 10 years are summarized and new approaches and remaining challenges to the optimal control of CMV infection and disease in transplant settings are highlighted.
Journal ArticleDOI
Clinical Diagnostic Testing for Human Cytomegalovirus Infections
Raymund R. Razonable,Naoki Inoue,Swetha G. Pinninti,Suresh B. Boppana,Tiziana Lazzarotto,Liliana Gabrielli,Giuliana Simonazzi,Philip E. Pellett,D. Scott Schmid +8 more
TL;DR: The issues, limitations, and application of diagnostic strategies for transplant recipients and congenital infection are summarized, including examples of screening programs for congenital HCMV that have been implemented at several centers in Japan, Italy, and the United States.
Journal ArticleDOI
Correlation of Cytomegalovirus (CMV) Disease Severity and Mortality With CMV Viral Burden in CMV-Seropositive Donor and CMV-Seronegative Solid Organ Transplant Recipients.
Jacqueline McBride,Daniel Sheinson,Jenny Jiang,Nicholas Lewin-Koh,Barbara G. Werner,Jennifer K. Chow,Xiaoning Wu,Jorge A. Tavel,David R. Snydman +8 more
TL;DR: Using specimens from studies preceding the antiviral prophylaxis era, CMV viral load was associated with severe CMV disease and death, supporting CMV Viral load quantification as a proxy for CMV Disease severity and disease-associated mortality end points in solid organ transplantation.
References
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