Nucleoside-analog resistance mutations in HIV-1 reverse transcriptase and their influence on polymerase fidelity and viral mutation rates

Int J Biochem Cell Biol. 2004 Sep;36(9):1716-34. doi: 10.1016/j.biocel.2004.02.025.


Nucleoside-analog inhibitors of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) were the first drugs used against the virus. It is long known that monotherapy with these and other drugs leads to the rapid development of viral resistance and it is being increasingly appreciated that a significant percentage of individuals receiving highly active antiretroviral therapy (HAART) also develop resistance. Considering the fact that RT is responsible both for optimal rate of replication and an accurate copying of the viral genome, the consequence of drug-resistance mutations in RT to the biochemistry of this enzyme and to the biology of the virus are critically important. The biochemistry of HIV-1 reverse transcriptase variants harboring nucleoside-analog resistance mutations has been studied extensively. In this review, we describe a number of studies into the polymerase fidelity of nucleoside-analog resistant HIV-1 reverse transcriptase as well as the mutation rate of HIV-1 harboring these mutations.

Publication types

  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Antiretroviral Therapy, Highly Active
  • DNA-Directed DNA Polymerase / genetics
  • DNA-Directed DNA Polymerase / metabolism
  • Drug Resistance, Multiple, Viral / genetics
  • HIV Infections / drug therapy
  • HIV Reverse Transcriptase / antagonists & inhibitors
  • HIV Reverse Transcriptase / chemistry
  • HIV Reverse Transcriptase / genetics*
  • HIV-1 / drug effects
  • HIV-1 / genetics*
  • Humans
  • Mutation*
  • Nucleosides / chemistry
  • Nucleosides / pharmacology
  • Reverse Transcriptase Inhibitors / chemistry
  • Reverse Transcriptase Inhibitors / pharmacology*
  • Virus Replication / genetics


  • Nucleosides
  • Reverse Transcriptase Inhibitors
  • HIV Reverse Transcriptase
  • DNA-Directed DNA Polymerase