Document Detail


Production of resistant HIV mutants during antiretroviral therapy.
MedLine Citation:
PMID:  10884399     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
HIV drug therapy often fails because of the appearance of multidrug-resistant virus. There are two possible scenarios for the outgrowth of multidrug-resistant virus in response to therapy. Resistant virus may preexist at low frequencies in drug-naive patients and is rapidly selected in the presence of drugs. Alternatively, resistant virus is absent at the start of therapy but is generated by residual viral replication during therapy. Currently available experimental methods are generally too insensitive to distinguish between these two scenarios. Here we use deterministic and stochastic models to investigate the origin of multidrug resistance. We quantify the probabilities that resistant mutants preexist, and that resistant mutants are generated during therapy. The models suggest that under a wide range of conditions, treatment failure is most likely caused by the preexistence of resistant mutants.
Authors:
R M Ribeiro; S Bonhoeffer
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Proceedings of the National Academy of Sciences of the United States of America     Volume:  97     ISSN:  0027-8424     ISO Abbreviation:  Proc. Natl. Acad. Sci. U.S.A.     Publication Date:  2000 Jul 
Date Detail:
Created Date:  2000-08-10     Completed Date:  2000-08-10     Revised Date:  2013-04-16    
Medline Journal Info:
Nlm Unique ID:  7505876     Medline TA:  Proc Natl Acad Sci U S A     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  7681-6     Citation Subset:  IM; X    
Affiliation:
Wellcome Trust Centre for the Epidemiology of Infectious Diseases, Department of Zoology, University of Oxford, South Parks Road, OX1 3PS, Oxford, United Kingdom.
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MeSH Terms
Descriptor/Qualifier:
Anti-HIV Agents / therapeutic use*
Computer Simulation
Drug Resistance, Microbial / genetics
HIV / genetics*
HIV Infections / virology*
Models, Genetic*
Mutation*
Stochastic Processes
Treatment Failure
Chemical
Reg. No./Substance:
0/Anti-HIV Agents
Comments/Corrections
Comment In:
Proc Natl Acad Sci U S A. 2000 Jul 18;97(15):8193-5   [PMID:  10899988 ]

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


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