Makindo Medical Notes

💊 Key Point: Rilpivirine is a well-tolerated, second-generation Non-Nucleoside Reverse Transcriptase Inhibitor (NNRTI) used as part of combination ART for HIV-1. ⚠️ Must be taken with food to ensure adequate absorption. Avoid co-administration with proton pump inhibitors (PPIs) as absorption is pH-dependent.

🧠 About

• Rilpivirine (RPV) is a second-generation NNRTI used in the management of HIV-1 infection.
• It is more potent and better tolerated than older NNRTIs such as efavirenz and nevirapine, with fewer CNS and hepatic side effects.
• Often co-formulated with tenofovir disoproxil fumarate (TDF) and emtricitabine (FTC) in single-tablet regimens (e.g. Eviplera®, Odefsey®).
• Always check the BNF for up-to-date dosing and interaction advice.

⚙️ Mode of Action

• Rilpivirine is a Non-Nucleoside Reverse Transcriptase Inhibitor (NNRTI).
• It binds to an allosteric site on the HIV-1 reverse transcriptase enzyme, causing a conformational change that inhibits viral DNA polymerase activity.
• It does not require intracellular phosphorylation and acts non-competitively, unlike nucleoside analogues.
• Less prone to resistance than earlier NNRTIs due to flexible binding kinetics and higher affinity for mutant reverse transcriptase enzymes.

💊 Indications & Dosing

• HIV-1 infection: 25 mg once daily with a main meal (to enhance absorption).
• May be used in treatment-naïve adults with baseline viral load < 100,000 copies/mL.
• Also used as a component of long-acting injectable therapy (with cabotegravir) for selected stable patients.

⚠️ Interactions

• Acid-reducing agents: PPIs (omeprazole, lansoprazole) markedly reduce absorption — contraindicated. H2 antagonists and antacids can be used with timing separation.
• Metabolised via CYP3A4 — avoid with potent inducers (e.g. rifampicin, carbamazepine, phenytoin, St John’s wort).
• Can be co-administered with most integrase inhibitors and NRTIs.
• Avoid combination with protease inhibitors unless specialist advice is sought.

⚕️ Cautions

• Baseline and periodic monitoring of hepatic function recommended.
• Use caution in patients with history of depression or CNS disorders — may worsen mood or sleep disturbances.
• Ensure adherence to meal timing — fasting significantly reduces bioavailability.
• Not suitable for patients with high baseline viral load (>100,000 copies/mL) due to higher risk of virological failure.

🚫 Contraindications

• Concurrent use with proton pump inhibitors.
• Severe hepatic impairment.
• Hypersensitivity to rilpivirine or formulation excipients.
• See BNF for comprehensive list of contraindicated drug combinations.

💥 Side Effects

• Common: Headache, insomnia, dizziness, rash, nausea.
• Psychiatric: Depression, anxiety, abnormal dreams.
• Hepatic: Mild elevations in transaminases; rare hepatotoxicity in co-infected patients.
• Metabolic: Hyperlipidaemia and redistribution of body fat (class effect of ART).

📖 Educational Summary

Rilpivirine exemplifies the evolution of NNRTIs — greater potency, reduced CNS side effects, and improved tolerability. Its requirement for **acidic gastric pH** makes it a good teaching example of how absorption kinetics influence drug design and patient education. Compared to efavirenz, rilpivirine has fewer neuropsychiatric effects but slightly lower potency in patients with high viral loads. It’s also available in innovative long-acting injectable formulations with cabotegravir, marking a shift toward **“treatment simplification”** and **adherence-friendly ART**.

📚 References

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