HIV-1 reverse transcriptase inhibitors

Appl Microbiol Biotechnol. 2007 Jun;75(4):723-37. doi: 10.1007/s00253-007-0919-7. Epub 2007 Mar 17.


Reverse transcriptase (RT) is one of the three enzymes encoded by the human immunodeficiency virus type 1 (HIV-1), the etiological agent of AIDS. Together with protease inhibitors, drugs inhibiting the RNA- and DNA-dependant DNA polymerase activity of RT are the major components of highly active antiretroviral therapy (HAART), which has dramatically reduced mortality and morbidity of people living with HIV-1/AIDS in developed countries. In this study, we focus on RT inhibitors approved by the US Food and Drugs Administration (FDA) or in phases II and III clinical trials. RT inhibitors belong to two main classes acting by distinct mechanisms. Nucleoside RT inhibitors (NRTIs) lack a 3' hydroxyl group on their ribose or ribose mimic moiety and thus act as chain terminators. Non-NRTIs bind into a hydrophobic pocket close to the polymerase active site and inhibit the chemical step of the polymerization reaction. For each class of inhibitors, we review the mechanism of action, the resistance mechanisms selected by the virus, and the side effects of the drugs. We also discuss the main perspectives for the development of new RT inhibitors.

Publication types

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

MeSH terms

  • Anti-HIV Agents / chemistry
  • Anti-HIV Agents / therapeutic use*
  • Anti-HIV Agents / toxicity
  • Clinical Trials as Topic
  • Drug Approval
  • Drug Design
  • Drug Resistance, Viral
  • HIV Infections / drug therapy*
  • HIV Reverse Transcriptase / antagonists & inhibitors*
  • HIV-1 / drug effects*
  • Humans
  • Nucleosides / chemistry
  • Nucleosides / therapeutic use
  • Nucleosides / toxicity
  • Phosphorylation
  • Reverse Transcriptase Inhibitors / chemistry
  • Reverse Transcriptase Inhibitors / therapeutic use*
  • Reverse Transcriptase Inhibitors / toxicity


  • Anti-HIV Agents
  • Nucleosides
  • Reverse Transcriptase Inhibitors
  • reverse transcriptase, Human immunodeficiency virus 1
  • HIV Reverse Transcriptase