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Use of Viral Load as a Surrogate Marker in Clinical Studies of Cytomegalovirus in Solid Organ Transplantation: A Systematic Review and Meta-analysis

2017; Oxford University Press; Volume: 66; Issue: 4 Linguagem: Inglês

10.1093/cid/cix793

1537-6591

Yoichiro Natori, Ali Alghamdi, Mahmood Tazari, Veronica Miller, Shahid Husain, Takashi Komatsu, Paul 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 L. Bowlin, Jennifer Brooks, Roy F. Chemaly, Sunwen Chou, Gavin Cloherty, William W. Cruikshank, Lesia K. Dropulic, Hermann Einsele, Jay Erdman, Gary A. Fahle, Lynn Fallon, Heather L. Gillis, Dimitri Gonzalez, Paul Griffiths, Kurt C. Gunter, Hans H. Hirsch, Aimee Hodowanec, Atul Humar, Peter Hunt, Filip Josephson, Takashi Komatsu, 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, Per Ljungman, Paula Isabelle Lodding, Jens Lundgren, Francisco Martínez-Murillo, Howard Mayer, Megan McCutcheon, John E. McKinnon, Thomas Mertens, Veronica Miller, Kevin J. Modarress, Johann Mols, Sally Mossman, Yoshihiko Murata, David Murawski, Jeffrey S. Murray, Yoichiro Natori, 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, Yu Dong, Bernhardt Zeiher,

Polyomavirus and related diseases

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.