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Updated: May 12, 2026

Quantitative Structure-Activity Relationship, Activity Prediction, and Molecular Dynamics of Non-nucleotide Reverse Transcriptase Inhibitors
Published on: May 9, 2025
Etravirine for the treatment of HIV/AIDS
1Department of Pharmaceutical and Pharmacological Sciences, Laboratory for Molecular Virology and Gene Therapy, Herestraat 49, 3000 KU Leuven, Belgium. Rik.Schrijvers@uzleuven.be
Introduction:
Etravirine (TMC125) is an orally administered second-generation non-nucleoside reverse transcriptase inhibitor (NNRTI) that is approved in treatment-experienced patients as addition to an optimized background therapy (OBT).
Areas Covered:
A Medline search was conducted of Phase II - IV clinical trials, as well as a review of abstracts from major HIV and infectious disease conferences from 2010 - 2013, involving etravirine.
Expert Opinion:
Etravirine is a well-tolerated NNRTI with a good safety profile and a higher genetic barrier for resistance compared to first-generation NNRTIs. Rash is a potential side effect but remains mostly mild to moderate. The necessity of taking it twice daily with food (200 mg bid.), potential pharmacokinetic interactions and low concentrations in the central nervous system (CNS) represent limitations. The efficacy of once daily etravirine (400 mg qid.) and the use in treatment modification/simplification strategies requires further research. Despite its favorable profile, etravirine is currently not sufficiently investigated nor approved for use in treatment-naïve patients which should be balanced against its potential as a backup NNRTI and the broad cross-resistance conferred by etravirine failure to other NNRTIs. Etravirine should be avoided following treatment failure with regimens containing rilpivirine, another second-generation NNRTI.
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