Detection of Ganciclovir Resistance in Patients with AIDS and Cytomegalovirus Retinitis: Correlation of Genotypic Methods with Viral Phenotype and Clinical Outcome
Departments of 1Ophthalmology, 2Medicine, and 3Pathology, School of Medicine, and 4Department of Epidemiology, Bloomberg School of Public Health, The Johns Hopkins University, Baltimore, Maryland
Background.
The cytomegalovirus (CMV) UL97 gene can be sequenced either from blood specimens directly amplified by polymerase chain reaction (PCR) or from culture isolates, to detect resistance to ganciclovir.
Methods.A prospective epidemiological study was conducted in which paired specimens were routinely obtained for sequencing of the UL97 gene from blood specimens (i.e., plasma and leukocytes) directly amplified by PCR and from CMV culture isolates. The specimens then were compared with each other and in terms of results of susceptibility testing and their association with progression of retinitis.
Results.A total of 845 paired specimens were obtained from 165 patients with AIDS and CMV retinitis. There typically was >90% agreement between the UL97 gene sequences from blood specimens directly amplified by PCR and those from culture isolates. The agreement between phenotypic resistance and the detection of UL97 mutations was >92% for PCR‐amplified blood specimens and >97% for culture isolates. Plasma and leukocytes performed similarly. Progression of retinitis was correlated with the detection of UL97 mutations in PCR‐amplified blood specimens, with adjusted odds ratios of 7.02 (
) for leukocytes, 9.11 (
) for plasma, and 17.6 for culture isolates (
).
Conclusions.Because blood specimens directly amplified by PCR can be analyzed more rapidly than can cultures (
48 h vs. 
4 weeks), sequencing the CMV UL97 gene from blood specimens directly amplified by PCR may be useful clinically.
Received 16 December 2005; accepted 2 February 2006; electronically published 10 May 2006.
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Online publication date: 15-Feb-2009.
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Financial support: National Eye Institute, National Institutes of Health (NIH; grants EY10268 and EY015643 to D.A.J.); National Institute for Research Resources, NIH (grant M01‐RR00052); Roche Laboratories (unrestricted grant).
Potential conflicts of interest: none reported.
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Study group members are listed after the text.