Makindo Medical Notes

💊 Key Point: Etravirine is a second-generation Non-Nucleoside Reverse Transcriptase Inhibitor (NNRTI) designed to retain activity against HIV strains resistant to older NNRTIs such as efavirenz and nevirapine. 🧠 Take after meals to enhance absorption. Monitor for rash and liver dysfunction.

🧠 About

• Etravirine is a second-generation NNRTI used as part of combination antiretroviral therapy (cART) for HIV-1 infection.
• It is particularly effective against HIV strains with NNRTI resistance mutations, owing to its flexible molecular structure that allows continued binding to the enzyme despite viral mutations.
• Always check the BNF entry for current dosing, contraindications, and interaction details.

⚙️ Mode of Action

• Member of the Non-Nucleoside Reverse Transcriptase Inhibitor (NNRTI) class.
• Binds to an allosteric site on HIV-1 reverse transcriptase, inducing a conformational change that inhibits DNA polymerase activity and viral replication.
• Unlike first-generation NNRTIs, etravirine’s structure allows multiple binding conformations — maintaining efficacy even when the virus mutates.

💊 Indications & Dosing

• HIV-1 infection: 200 mg twice daily.
• Take after food to optimise absorption and maintain stable plasma concentrations.
• Always used as part of a combination regimen with other antiretrovirals.

⚠️ Interactions

• Metabolised by CYP3A4, CYP2C9, and CYP2C19 → complex interaction profile.
• Can both induce and inhibit cytochrome enzymes — consult interaction tables carefully.
• May reduce plasma levels of some protease inhibitors (e.g. atazanavir, fosamprenavir) unless combined with ritonavir boosting.
• Avoid with strong enzyme inducers (e.g. rifampicin, carbamazepine, phenytoin) — may cause loss of efficacy.
• See BNF for detailed drug–drug interactions.

⚕️ Cautions

• Monitor for rash and hypersensitivity reactions — rare cases of Stevens–Johnson syndrome reported.
• Hepatic impairment: increased drug exposure — use with caution and monitor LFTs.
• Pregnancy: limited safety data; use only if benefits outweigh risks.
• Ensure adherence and monitor viral load regularly to prevent resistance development.

🚫 Contraindications

• Severe hepatic impairment.
• Hypersensitivity to etravirine or any excipients.
• Concurrent use with potent CYP inducers (e.g. rifampicin, St John’s wort).
• See BNF for comprehensive list.

💥 Side Effects

• Common: Rash (usually mild), nausea, diarrhoea, headache.
• Occasional: Elevated transaminases, fatigue, peripheral neuropathy.
• Rare but serious: Stevens–Johnson syndrome, erythema multiforme, hepatic failure.

📖 Educational Summary

Etravirine represents the evolution of the NNRTI class — designed with molecular flexibility to overcome common resistance mutations seen with efavirenz and nevirapine. It is particularly useful in patients with prior NNRTI exposure or treatment failure, often combined with boosted protease inhibitors. From a teaching standpoint, it’s an elegant example of **rational drug design**, where subtle molecular adjustments restore drug efficacy against resistant viral targets. Clinically, always remember: it’s **taken after food**, has **complex interactions**, and can cause **skin reactions** requiring careful early review.

📚 References

• Etravirine – British National Formulary
• BHIVA Guidelines for the Treatment of HIV-1 Positive Adults (2023)
• European AIDS Clinical Society (EACS) Guidelines, 2023
• Harrison’s Principles of Internal Medicine, 21st Edition – Antiretroviral Pharmacology