Development and significance of nucleoside drug resistance in infection caused by the human immunodeficiency virus type 1

Clin Invest Med. 1994 Jun;17(3):226-43.

Abstract

Nucleoside antagonists of human immunodeficiency virus (HIV) reverse transcriptase (RT) activity have been commonly used in the therapy of HIV-associated disease. The prolonged use of such drugs has led to the development of HIV variants that display resistance against these compounds. HIV drug resistance has been documented clinically for each of the following nucleosides: 3'-azido-3'-deoxythymidine (AZT; zidovudine, ZDV), 2',3'-dideoxyinosine (ddI; didanosine), and 2',3'-dideoxycytidine (ddC; zalcitabine). In addition, resistance has been demonstrated against a series of non-nucleoside inhibitors of the viral RT. Several groups have documented that a series of point mutations within the HIV pol gene, that encodes the RT enzyme, is responsible for HIV drug resistance. Diminished sensitivity to anti-viral drugs results from both the selective pressure exerted by these compounds in individuals receiving prolonged therapy and the error-prone nature of the viral RT itself, thus permitting the outgrowth of mutated forms. Patients suffering from both disease progression and/or low CD4 counts are most likely to develop HIV drug resistance.

Publication types

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

MeSH terms

  • Acquired Immunodeficiency Syndrome / drug therapy
  • Acquired Immunodeficiency Syndrome / microbiology
  • Antiviral Agents / pharmacology*
  • Drug Resistance
  • HIV Reverse Transcriptase
  • HIV-1 / drug effects*
  • HIV-1 / enzymology
  • HIV-1 / genetics
  • Humans
  • Mutation
  • Nucleosides / pharmacology*
  • Reverse Transcriptase Inhibitors

Substances

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