Makindo Medical Notes

⚠️ Key Point: Nevirapine is a first-generation Non-Nucleoside Reverse Transcriptase Inhibitor (NNRTI) with good CNS penetration but significant risk of hepatotoxicity and rash. 🔬 Avoid initiation in patients with high baseline CD4 counts due to increased risk of severe hepatic reactions.

🧠 About

• Nevirapine is a Non-Nucleoside Reverse Transcriptase Inhibitor (NNRTI) used in the treatment of HIV-1 infection as part of combination antiretroviral therapy (cART).
• It was one of the earliest NNRTIs, now largely superseded by newer agents (e.g. efavirenz, doravirine) due to its toxicity profile.
• Always check the BNF entry for up-to-date dosing and monitoring guidance.

⚙️ Mode of Action

• Binds directly and non-competitively to the HIV-1 reverse transcriptase enzyme at an allosteric site, causing a conformational change that blocks DNA synthesis.
• Inhibits viral replication without requiring phosphorylation (unlike NRTIs).
• Demonstrates good CNS penetration, making it effective in reducing viral load within cerebrospinal fluid.

💊 Indications & Dosing

• HIV-1 infection:
  • Start with 200 mg once daily for 14 days (“lead-in” period) to reduce rash risk, then increase to 200 mg twice daily.
• No food restrictions.
• Always used in combination with other antiretrovirals (usually NRTI backbone).

⚠️ Interactions

• Potent inducer of cytochrome P450 (especially CYP3A4) — may reduce plasma levels of many co-administered drugs.
• Reduces concentrations of oral contraceptives, azole antifungals, and some protease inhibitors.
• Avoid co-administration with other hepatotoxic agents where possible.
• See BNF for full list of drug–drug interactions.

⚕️ Cautions

• Monitor LFTs closely for the first 18 weeks — most hepatic events occur early.
• Use with caution in pre-existing hepatic impairment or Hepatitis B/C co-infection.
• Rash is common but may rarely progress to Stevens–Johnson syndrome or TEN — stop immediately if severe rash develops.

🚫 Contraindications

• High baseline CD4 counts — risk of severe hepatotoxicity:
  • Men: CD4 > 400 cells/mm³
  • Women: CD4 > 250 cells/mm³
• Moderate to severe hepatic impairment.
• Hypersensitivity to nevirapine or excipients.

💥 Side Effects

• Common: Rash (often mild and self-limiting), nausea, fatigue, headache.
• Serious: Hepatotoxicity (can be fatal), Stevens–Johnson syndrome, toxic epidermal necrolysis.
• Metabolic: Lipodystrophy, hyperlipidaemia, insulin resistance (with long-term use).
• Note: Hepatotoxicity risk is greatest in the first 6–12 weeks and in patients with high CD4 counts or female sex.

📖 Educational Summary

Nevirapine is a landmark drug in the history of HIV therapy — one of the first NNRTIs to demonstrate sustained viral suppression. Its role today is mainly historical or limited to specific resource-limited settings, as safer alternatives exist. The hallmark teaching point is the **immunologically driven hepatotoxicity**, which is paradoxically more common in patients with higher CD4 counts — a pattern unique to this class. It also illustrates the classic mechanism of NNRTIs: **non-competitive binding** to reverse transcriptase rather than chain termination. In UK and European guidelines, it’s now rarely initiated but remains important for understanding the evolution of ART toxicity management.

📚 References

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