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JAC Advance Access originally published online on September 1, 2003
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Journal of Antimicrobial Chemotherapy (2003) 52, 547-550
© 2003 The British Society for Antimicrobial Chemotherapy

Leading Article

Nucleoside reverse transcriptase inhibitors and HIV mutagenesis

Nancy A. Jewell1, Renxiang Chen2, Raquel Raices3 and Louis M. Mansky1,2,3,4,*

1 Molecular, Cellular and Developmental Biology Graduate Program, Ohio State University, Columbus, OH 43210; 2 Ohio State Biochemistry Graduate Program, Ohio State University, Columbus, OH 43210; 3 Integrated Biomedical Science Graduate Program, Ohio State University, Columbus, OH 43210; 4 Department of Molecular Virology, Immunology, and Medical Genetics, Center for Retrovirus Research, and Comprehensive Cancer Center Ohio State University Medical Center, Columbus, OH 43210, USA

Keywords: NRTIs, resistance, evolution, mutagenesis, retrovirus

The first 150 words of the full text of this article appear below.


   Introduction
 
Potent antiretroviral therapy (ART) of HIV-1 infection with antiretroviral drugs consisting of nucleoside reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs) and protease inhibitors (PIs) has dramatically reduced the rate of HIV- and AIDS-related morbidity and mortality. The lack of patient compliance to drug administration results in suboptimal therapy. Suboptimal drug therapy can lead to drug resistance, which limits the clinical benefit of drug treatment and can select for new variant viruses with altered virulence and tropism.

In this leading article, we discuss literature that shows a correlation between the evolution of drug resistance and increased HIV and other pathogen mutation rates. In the case of HIV, NRTIs and NRTI drug resistance can increase HIV mutation rates, and can act together to further increase these rates. These increased mutation rates predict that drug failure during initial treatment could increase the probability of subsequent drug therapy failures due to the . . . [Full Text of this Article]


   NRTIs, drug resistance and HIV mutagenesis
 

   Salvage therapy and increased HIV mutagenesis
 

   Therapeutic application of increased HIV-1 mutagenesis by NRTIs
 

   Antimicrobial drug resistance and increased pathogen mutation rates
 

   Conclusions
 

   Acknowledgements
 

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