Etravirine
NNRTIs
Non-nucleoside reverse transcriptase inhibitors (NNRTIs)
A second-generation NNRTI that stays active against many HIV strains resistant to efavirenz or nevirapine. Rash is its key side effect.
Quick facts
- Group
- Non-nucleoside reverse transcriptase inhibitors (NNRTIs)
- Target
- HIV-1 reverse transcriptase (NNRTI pocket)
- Used for
- HIV-1 infection
- Key effects
- Rash · Diarrhoea and nausea · Body fat changes
- Monitor
- Skin during the first weeks · Liver tests
- ATC
- J05AG04
No doses: the clinician sets them by the current guideline.
Mechanism of action
The figure shows etravirine (TMC125) in the NNRTI-binding pocket of HIV-1 reverse transcriptase.
Etravirine is a diarylpyrimidine that binds the non-nucleoside pocket of HIV-1 reverse transcriptase, close to the active site, and locks the enzyme in an inactive shape. Its flexible structure lets it adapt to the pocket when common NNRTI mutations are present, so many strains resistant to first-generation NNRTIs remain sensitive.
- Etravirine binds the NNRTI pocket of reverse transcriptase
- The enzyme is locked in an inactive shape
- Viral RNA is not copied into DNA
- Flexibility lets it fit mutated pockets
Indications
- HIV-1 infection in treatment-experienced patients with NNRTI-resistant virus, with other active antiretrovirals HIV infection and AIDS →
Adverse effects
Common
- Rash, usually in the first weeks
- Diarrhoea and nausea
- Tingling or numbness in hands or feet
- Body fat changes
Contraindications
- Severe hypersensitivity or skin reaction to etravirine
- Other NNRTIs
- Some boosted protease inhibitors (tipranavir, fosamprenavir or atazanavir with ritonavir)
Key interactions
- Other NNRTIs
- Not combined
- Tipranavir, fosamprenavir or atazanavir with ritonavir
- Unpredictable levels; not combined
- Maraviroc
- Etravirine lowers maraviroc; the regimen is adjusted
- CYP2C9 and CYP2C19 substrates; CYP3A4 substrates
- Levels of the first may rise and of the second may fall; each combination is checked
What is monitored
- Skin during the first weeks
- Liver tests
- HIV viral load and resistance testing
Administration and safety
- Oral, twice a day, after a meal
- Tablets can be dispersed in water if they cannot be swallowed; the mixture is drunk at once
Pregnancy and breastfeeding
Human data are limited; the HIV team weighs benefit and risk.
Nursing care
- Teach to stop and seek care for a rash with fever, blisters, mouth sores or eye swelling
- Check every new medicine for interactions
- Teach to report jaundice or dark urine
- Reinforce taking it after food
Pharmacokinetics
- Absorption
- Oral; taken after a meal because food increases absorption
- Metabolism
- Liver CYP3A4, CYP2C9 and CYP2C19; induces CYP3A4 and glucuronidation and inhibits CYP2C9 and CYP2C19
Test yourself
Think of the answer, then tap the question to see it.
Why is etravirine active against many efavirenz-resistant strains?
Its flexible structure adapts to the mutated NNRTI pocket.
What is the most important adverse effect of etravirine?
Rash, which can rarely be severe (Stevens-Johnson syndrome or toxic epidermal necrolysis).
Should etravirine be taken fasting or after a meal?
After a meal, because food increases absorption.
Connections
← Back to the class: Non-nucleoside reverse transcriptase inhibitors (NNRTIs)
Educational content on how drugs work; not a prescribing guide and no substitute for a health professional's advice. No doses are given.
Sources: Etravirine: MedlinePlus Drug Information (MedlinePlus (U.S. National Library of Medicine), 2026); HIV-1 Reverse Transcriptase in Complex with TMC125 (RCSB Protein Data Bank, 2010); ATCDDD - ATC/DDD Index (WHO Collaborating Centre for Drug Statistics Methodology, 2026).
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Representative model, for educational purposes only.