Abstract
The evolution of antiretroviral drug resistance is a major problem in the treatment of human immunodeficiency virus type 1 (HIV-1) infection. Drug therapy failure is associated with accumulation of drug resistance mutations and results in the development of drug resistance. Drugs targeted against reverse transcriptase (RT) as well as drug-resistant RT have been shown to increase HIV-1 mutation frequencies. Furthermore, combinations of drug and drug-resistant RT can increase virus mutation frequencies in a multiplicative manner. The evolution of drug resistance also alters virus fitness. The correlation of increased HIV-1 mutation rates with the evolution of antiretroviral drug resistance indicates that drug failure could increase the likelihood of further resistance evolving from subsequent drug regimens. These observations parallel studies from microbial systems that provide evidence for a correlation between drug resistance development and increased pathogen mutation rates. Although increased mutan t frequencies may be detrimental to effective therapy, the lethal mutagenesis of the HIV-1 genome may provide a new means for antiretroviral therapy.
Keywords: hiv infection, nucleoside reverse, transcriptase inhibitors, protease inhibitors, replication cycle, genomes, antiretroviral drugs, azt-resistant virus, mutagenesis, antimicrobial drug
Current Pharmaceutical Design
Title: Drug Resistance, Virus Fitness and HIV-1 Mutagenesis
Volume: 10 Issue: 32
Author(s): Renxiang Chen, Miguel E. Quinones-Mateu and Louis M. Mansky
Affiliation:
Keywords: hiv infection, nucleoside reverse, transcriptase inhibitors, protease inhibitors, replication cycle, genomes, antiretroviral drugs, azt-resistant virus, mutagenesis, antimicrobial drug
Abstract: The evolution of antiretroviral drug resistance is a major problem in the treatment of human immunodeficiency virus type 1 (HIV-1) infection. Drug therapy failure is associated with accumulation of drug resistance mutations and results in the development of drug resistance. Drugs targeted against reverse transcriptase (RT) as well as drug-resistant RT have been shown to increase HIV-1 mutation frequencies. Furthermore, combinations of drug and drug-resistant RT can increase virus mutation frequencies in a multiplicative manner. The evolution of drug resistance also alters virus fitness. The correlation of increased HIV-1 mutation rates with the evolution of antiretroviral drug resistance indicates that drug failure could increase the likelihood of further resistance evolving from subsequent drug regimens. These observations parallel studies from microbial systems that provide evidence for a correlation between drug resistance development and increased pathogen mutation rates. Although increased mutan t frequencies may be detrimental to effective therapy, the lethal mutagenesis of the HIV-1 genome may provide a new means for antiretroviral therapy.
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Cite this article as:
Chen Renxiang, Quinones-Mateu E. Miguel and Mansky M. Louis, Drug Resistance, Virus Fitness and HIV-1 Mutagenesis, Current Pharmaceutical Design 2004; 10 (32) . https://dx.doi.org/10.2174/1381612043382404
DOI https://dx.doi.org/10.2174/1381612043382404 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
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