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Related Experiment Video

Updated: Jun 16, 2026

Quantitative Structure-Activity Relationship, Activity Prediction, and Molecular Dynamics of Non-nucleotide Reverse Transcriptase Inhibitors
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[Etravirine: genetic barrier and resistance development].

Josep M Llibre1, José Ramón Santos, Bonaventura Clotet

  • 1Hospital Universitari Germans Trias i Pujol, Badalona, Barcelona, España. jmllibre@flsida.org

Enfermedades Infecciosas Y Microbiologia Clinica
|February 2, 2010
PubMed
Summary

Etravirine (ETR) requires multiple mutations for complete resistance, unlike older NNRTIs. Genotypic data accurately predict ETR activity, with some mutations causing hypersusceptibility.

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Published on: December 9, 2015

Area of Science:

  • HIV/AIDS research
  • Antiretroviral therapy

Background:

  • First-generation non-nucleoside reverse transcriptase inhibitors (NNRTIs) often develop rapid resistance.
  • Etravirine (ETR) presents a higher barrier to resistance compared to earlier NNRTIs.

Purpose of the Study:

  • To evaluate the resistance profile of etravirine (ETR) against HIV-1 reverse transcriptase mutations.
  • To assess the utility of genotypic data in predicting ETR activity and clinical outcomes.

Main Methods:

  • Analysis of mutations conferring resistance to ETR.
  • Validation of genotypic scoring systems against phenotypic resistance and clinical data from DUET studies.

Main Results:

  • Complete resistance to ETR necessitates the accumulation of multiple mutations.
  • Specific mutations selected by nevirapine/efavirenz can impact ETR activity.
  • Genotypic data, using validated scoring systems, accurately predict ETR activity.
  • Certain mutations, like T69D/N and M184I/V, can lead to hypersusceptibility to ETR.

Conclusions:

  • Etravirine (ETR) demonstrates a high barrier to complete resistance.
  • Genotypic resistance testing is a reliable tool for predicting ETR efficacy.
  • Early discontinuation of failing first-generation NNRTIs is crucial to preserve ETR activity.