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- Title
Impact of Genetic Polymorphisms in Cytomegalovirus Glycoprotein B on Outcomes in Solid-Organ Transplant Recipients with Cytomegalovirus Disease.
- Authors
Manuel, Oriol; Åsberg, Anders; Xiaoli Pang; Rollag, Halvor; Emery, Vincent C.; Preiksaitis, Jutta K.; Kumar, Deepali; Pescovitz, Mark D.; Bignamini, Angelo A.; Hartmann, Anders; Jardine, Alan G.; Humar, Atul
- Abstract
Background. It is unknown whether specific viral polymorphisms affect in vivo therapeutic response in patients with cytomegalovirus (CMV) disease. Polymorphisms in the CMV glycoprotein B (gB) gene allow discrimination of 4 distinct genotypes (gB1-gB4). We assessed the influence of gB genotypes on the clinical and virologic outcome of CMV disease. Methods. Solid-organ transplant recipients enrolled in a multicenter trial of CMV disease treatment (VICTOR study) were included in this study. CMV gB genotyping was performed using quantitative real-time polymerase chain reaction at day 0 (start of antiviral therapy). Results. Among 239 patients with CMV disease, the prevalence of gB strain types was 26% for gB1, 10% for gB2, 10% for gB3, and 5% for gB4, whereas mixed infections were present in 49%. Donor-seropositive/recipientseropositive patients were more likely to have mixed gB infection than donor-seropositive/recipient-seronegative patients (40% vs. 12%; ). Median baseline viral P < .001 loads were higher and time to viral eradication was longer (P = .005 and Pp.026, respectively) for mixed infection versus infection with a single genotype. In a multivariate model, mixed gB infection was a significant predictor of failure to eradicate virus by day 21 (mixed vs single genotype; odds ratio, 2.66; 95% confidence interval, 1.31-5.38; P = .007) after controlling for baseline viral load, CMV serostatus at baseline, ganciclovir resistance, and antiviral treatment. No effect of gB genotype was seen on virologic or clinical CMV recurrence. Conclusions. No specific gB genotype appears to confer a specific CMV virulence advantage. However, mixed gB genotype infections are associated with higher viral loads and delayed viral clearance.
- Subjects
GENETIC polymorphisms; CYTOMEGALOVIRUS diseases; GLYCOPROTEINS; TRANSPLANTATION of organs, tissues, etc.; POLYMERASE chain reaction; ANTIVIRAL agents; MICROBIAL virulence; GANCICLOVIR; VIRAL disease treatment
- Publication
Clinical Infectious Diseases, 2009, Vol 49, Issue 8, p1160
- ISSN
1058-4838
- Publication type
Article
- DOI
10.1086/605633