Drug resistance, virus fitness and HIV-1 mutagenesis

Renxiang Chen, Miguel E. Quinones-Mateu, Louis M. Mansky

Research output: Contribution to journalReview article

35 Scopus citations

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 mutant frequencies may be detrimental to effective therapy, the lethal mutagenesis of the HIV-1 genome may provide a new means for antiretroviral therapy.

Original languageEnglish (US)
Pages (from-to)4065-4070
Number of pages6
JournalCurrent pharmaceutical design
Volume10
Issue number32
DOIs
StatePublished - 2004

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