Evolution of mutations conferring multidrug resistance during prophylaxis and therapy for cytomegalovirus disease

Sunwen Chou, Gail Marousek, Susan Guentzel, Stephen E. Follansbee, Margaret E. Poscher, Jacob P. Lalezari, Richard C. Miner, W. Lawrence Drew

Research output: Contribution to journalArticle

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Abstract

In a human immunodeficiency virus-infected subject cytomegalovirus (CMV) isolated 9 months after the patient began oral ganciclovir prophylaxis was resistant to ganciclovir and cidofovir and contained mutations in both UL97 and Pol coding regions. At 1 year, retinitis developed, which progressed despite intravenous ganciclovir followed by foscarnet and then cidofovir. A subsequent buffy coat virus isolate was resistant to all three drugs and contained new mutations in UL97 and Pol. By individually transferring the observed mutations to laboratory strain AD169, it was shown that a mutation at codon 603 of UL97 conferred resistance to ganciclovir, a mutation at codon 412 of Pol conferred resistance to both ganciclovir and cidofovir, and a mutation at codon 802 of Pol conferred resistance to ganciclovir and foscarnet. This case illustrates the development of multidrug resistance during prolonged exposure to antiviral therapy for CMV and cross-resistance arising from point mutations in the CMV Pol gene.

Original languageEnglish (US)
Pages (from-to)786-789
Number of pages4
JournalJournal of Infectious Diseases
Volume176
Issue number3
StatePublished - 1997
Externally publishedYes

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Ganciclovir
Multiple Drug Resistance
Cytomegalovirus
Mutation
Codon
Foscarnet
Therapeutics
pol Genes
Retinitis
Point Mutation
Antiviral Agents
HIV
Viruses
Pharmaceutical Preparations
cidofovir

ASJC Scopus subject areas

  • Public Health, Environmental and Occupational Health
  • Immunology

Cite this

Chou, S., Marousek, G., Guentzel, S., Follansbee, S. E., Poscher, M. E., Lalezari, J. P., ... Drew, W. L. (1997). Evolution of mutations conferring multidrug resistance during prophylaxis and therapy for cytomegalovirus disease. Journal of Infectious Diseases, 176(3), 786-789.

Evolution of mutations conferring multidrug resistance during prophylaxis and therapy for cytomegalovirus disease. / Chou, Sunwen; Marousek, Gail; Guentzel, Susan; Follansbee, Stephen E.; Poscher, Margaret E.; Lalezari, Jacob P.; Miner, Richard C.; Drew, W. Lawrence.

In: Journal of Infectious Diseases, Vol. 176, No. 3, 1997, p. 786-789.

Research output: Contribution to journalArticle

Chou, S, Marousek, G, Guentzel, S, Follansbee, SE, Poscher, ME, Lalezari, JP, Miner, RC & Drew, WL 1997, 'Evolution of mutations conferring multidrug resistance during prophylaxis and therapy for cytomegalovirus disease', Journal of Infectious Diseases, vol. 176, no. 3, pp. 786-789.
Chou, Sunwen ; Marousek, Gail ; Guentzel, Susan ; Follansbee, Stephen E. ; Poscher, Margaret E. ; Lalezari, Jacob P. ; Miner, Richard C. ; Drew, W. Lawrence. / Evolution of mutations conferring multidrug resistance during prophylaxis and therapy for cytomegalovirus disease. In: Journal of Infectious Diseases. 1997 ; Vol. 176, No. 3. pp. 786-789.
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