New developments in the chemotherapy of lentivirus (human immunodeficiency virus) infections: sensitivity/resistance of HIV-1 to non-nucleoside HIV-1-specific inhibitors

Ann N Y Acad Sci. 1994 Jun 6:724:438-56. doi: 10.1111/j.1749-6632.1994.tb38946.x.


Of the different steps of the HIV replicative cycle, the reverse transcription step has received most attention as a target for chemotherapeutic intervention. The reverse transcriptase (RT) can be blocked by both nucleoside (nucleotide) and non-nucleoside type of inhibitors. Whereas the former act as competitive inhibitors with respect to the natural substrates or alternate substrates (chain terminators), the latter act allosterically with a non-substrate binding site of the enzyme. Several non-nucleoside types of RT inhibitors have proved to inhibit HIV-1 replication at nanomolar concentrations that are 10(4)- to 10(5)-fold lower than the cytotoxic concentrations. Although a non-nucleoside HIV-1-specific RT inhibitor may rapidly select for virus-drug resistance in cell culture, the resulting mutant strain may or may not show cross-resistance, and in some instances even hypersensitivity, to other HIV-specific RT inhibitors. When used at the appropriate concentrations, HIV-1-specific RT inhibitors are able to completely shut off ("knock-out") virus replication in vitro, under conditions where dideoxynucleoside analogues such as AZT fail to do so. This apparent "sterilizing effect" achieved by the non-nucleoside type of HIV-1-specific RT inhibitors opens new perspectives for the treatment of HIV infections in patients.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Acquired Immunodeficiency Syndrome / drug therapy*
  • Antiviral Agents / therapeutic use*
  • Drug Resistance, Microbial
  • HIV Reverse Transcriptase
  • HIV-1 / enzymology
  • Humans
  • Nucleosides / pharmacology
  • Reverse Transcriptase Inhibitors


  • Antiviral Agents
  • Nucleosides
  • Reverse Transcriptase Inhibitors
  • HIV Reverse Transcriptase