Molecular basis of human immunodeficiency virus drug resistance: An update

Antiretroviral therapy has led to a significant decrease in human immunodeficiency virus (HIV)-related mortality. Approved antiretroviral drugs target different steps of the viral life cycle including viral entry (coreceptor antagonists and fusion inhibitors), reverse transcription (nucleoside and n...

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Bibliographic Details
Published in:Antiviral research 2010, Vol.85 (1), p.210-231
Main Author: Menéndez-Arias, Luis
Format: Article
Language:English
Subjects:
Anti-HIV Agents - pharmacology
DNA polymerase
Drug resistance
Drug Resistance, Viral
HIV
HIV - drug effects
HIV - genetics
Human immunodeficiency virus
Humans
Mutation, Missense
Phosphorolysis
Reverse transcriptase
Thymidine analogues
Viral Proteins - genetics
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Summary:Antiretroviral therapy has led to a significant decrease in human immunodeficiency virus (HIV)-related mortality. Approved antiretroviral drugs target different steps of the viral life cycle including viral entry (coreceptor antagonists and fusion inhibitors), reverse transcription (nucleoside and non-nucleoside inhibitors of the viral reverse transcriptase), integration (integrase inhibitors) and viral maturation (protease inhibitors). Despite the success of combination therapies, the emergence of drug resistance is still a major factor contributing to therapy failure. Viral resistance is caused by mutations in the HIV genome coding for structural changes in the target proteins that can affect the binding or activity of the antiretroviral drugs. This review provides an overview of the molecular mechanisms involved in the acquisition of resistance to currently used and promising investigational drugs, emphasizing the structural role of drug resistance mutations. The optimization of current antiretroviral drug regimens and the development of new drugs are still challenging issues in HIV chemotherapy. This article forms part of a special issue of Antiviral Research marking the 25th anniversary of antiretroviral drug discovery and development, Vol 85, issue 1, 2010.
ISSN:0166-3542
1872-9096
DOI:10.1016/j.antiviral.2009.07.006