Evolution of Mutations Conferring Multidrug Resistance during Prophylaxis and Therapy for Cytomegalovirus Disease
| Autor: | Stephen E. Follansbee, W. Lawrence Drew, Jacob Lalezari, R C Miner, Gail I. Marousek, Susan Guentzel, Sunwen Chou, Margaret E. Poscher |
|---|---|
| Rok vydání: | 1997 |
| Předmět: |
Adult
Male Ganciclovir Foscarnet Human cytomegalovirus Anti-HIV Agents viruses Organophosphonates Cytomegalovirus Retinitis Biology Antiviral Agents Virus Cytosine chemistry.chemical_compound Organophosphorus Compounds medicine Humans Immunology and Allergy Recombination Genetic AIDS-Related Opportunistic Infections Point mutation virus diseases Drug Resistance Microbial RNA-Directed DNA Polymerase Sequence Analysis DNA biochemical phenomena metabolism and nutrition medicine.disease Virology Drug Resistance Multiple Multiple drug resistance Phosphotransferases (Alcohol Group Acceptor) Infectious Diseases chemistry Cytomegalovirus Infections Mutation Drug Therapy Combination Cidofovir medicine.drug |
| Zdroj: | The Journal of Infectious Diseases. 176:786-789 |
| ISSN: | 1537-6613 0022-1899 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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