Mutagenic outcome of combined antiviral drug treatment during human immunodeficiency virus type 1 replication

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26 Scopus citations

Abstract

The development of antiviral drug resistance is an important problem in the treatment of human immunodeficiency virus type 1 (HIV-1) infection. Potent antiretroviral therapy (ART) is currently used for treatment, and typically consists of at least two reverse transcriptase (RT) inhibitors. To assess the impact of combination therapy on HIV-1 mutagenesis, the mutagenic outcome of combined drug treatment was determined with several different RT drug combinations. Significant increases in HIV-1 mutant frequencies were observed with combinations of nucleoside RT inhibitors as well as in combinations where nucleoside inhibitors were used along with hydroxyurea, a drug known to deplete nucleotide pools in cells. This indicates that combinations of RT drugs can act together to further increase HIV-1 mutant frequencies, which could have important implications for virus population dynamics and could compromise drug therapy regimens.

Original languageEnglish (US)
Pages (from-to)116-121
Number of pages6
JournalVirology
Volume307
Issue number1
DOIs
StatePublished - Mar 1 2003
Externally publishedYes

Bibliographical note

Funding Information:
I thank L. Gajary for technical assistance and D. Pearl for helpful discussions. This research was supported by Public Health Service Grant GM56615.

Keywords

  • Drug
  • Evolution
  • Mutagenesis
  • Nucleoside
  • Polymerase

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