Document Detail


Detection of ganciclovir resistance in patients with AIDS and cytomegalovirus retinitis: correlation of genotypic methods with viral phenotype and clinical outcome.
MedLine Citation:
PMID:  16703517     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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 (P=.002) for leukocytes, 9.11 (P=.02) for plasma, and 17.6 for culture isolates (P<.0001). CONCLUSIONS: Because blood specimens directly amplified by PCR can be analyzed more rapidly than can cultures (< or =48 h vs. > or =4 weeks), sequencing the CMV UL97 gene from blood specimens directly amplified by PCR may be useful clinically.
Authors:
Douglas A Jabs; Barbara K Martin; Michelle O Ricks; Michael S Forman;
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2006-05-10
Journal Detail:
Title:  The Journal of infectious diseases     Volume:  193     ISSN:  0022-1899     ISO Abbreviation:  J. Infect. Dis.     Publication Date:  2006 Jun 
Date Detail:
Created Date:  2006-05-16     Completed Date:  2006-07-13     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0413675     Medline TA:  J Infect Dis     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1728-37     Citation Subset:  AIM; IM    
Affiliation:
Department of Ophthalmology, School of Medicine, The Johns Hopkins University, Baltimore, Maryland, USA. djabs@jhmi.edu
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MeSH Terms
Descriptor/Qualifier:
AIDS-Related Opportunistic Infections / drug therapy,  virology*
Acquired Immunodeficiency Syndrome / complications,  drug therapy
Adult
Antiretroviral Therapy, Highly Active
Cytomegalovirus / drug effects*,  genetics*,  isolation & purification
Cytomegalovirus Retinitis / drug therapy,  virology*
DNA, Viral / genetics
Disease Progression
Drug Resistance, Viral / genetics*
Female
Ganciclovir / pharmacology*,  therapeutic use
Humans
Leukocytes / virology
Male
Microbial Sensitivity Tests
Mutation
Phosphotransferases (Alcohol Group Acceptor) / genetics
Plasma / virology
Polymerase Chain Reaction
Sequence Analysis, DNA
Grant Support
ID/Acronym/Agency:
EY015643/EY/NEI NIH HHS; EY10268/EY/NEI NIH HHS; M01-RR00052/RR/NCRR NIH HHS
Chemical
Reg. No./Substance:
0/DNA, Viral; 82410-32-0/Ganciclovir; EC 2.7.1.-/Phosphotransferases (Alcohol Group Acceptor); EC 2.7.1.-/ganciclovir kinase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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