Pharmacology · Non-nucleoside reverse transcriptase inhibitors (NNRTIs)

Rilpivirine !

A second-generation NNRTI. It is absorbed only with food and stomach acid; there is also a long-acting injectable form.

Updated 2026-11-01

Class: Non-nucleoside reverse transcriptase inhibitors (NNRTIs)
Enzyme: HIV-1 reverse transcriptase (NNRTI pocket)
ATC code: J05AG05

Also called: RPV

HIV-1 reverse transcriptase (NNRTI pocket)Rilpivirine

The figure shows rilpivirine in the allosteric pocket of HIV-1 reverse transcriptase.

Target in 3D: HIV-1 reverse transcriptase (NNRTI pocket). PDB structure 2ZD1 (RCSB PDB, public domain). View the structure at RCSB PDB

Mechanism of action

A flexible NNRTI that fits the allosteric pocket of reverse transcriptase even when the pocket changes shape, so it keeps activity against some mutations that defeat efavirenz and nevirapine.

It adapts to the allosteric pocket of reverse transcriptase
It locks the enzyme
Viral DNA synthesis stops

Pharmacokinetics

Absorption: Needs food and an acidic stomach to be absorbed
Metabolism: Liver, by CYP3A

Indications

HIV-1 infection, combined with other antiretrovirals, in people without very high viral load HIV infection and AIDS →
As a long-acting injectable with cabotegravir to maintain viral suppression HIV infection and AIDS →

Adverse effects

Common

Headache
Insomnia
Rash
Depressive symptoms

Contraindications

Proton pump inhibitors
Strong CYP3A inducers: rifampicin, carbamazepine, oxcarbazepine, phenytoin, St John's wort, among others

Key interactions

Proton pump inhibitors: They raise gastric pH and rilpivirine is not absorbed: contraindicated
Antacids and H2 blockers: Reduce absorption; doses are separated in time
QT-prolonging drugs: Alternatives are preferred

What is monitored

Viral load and CD4
Mood
Liver tests

Administration and safety

By mouth, always with a meal
Check the medication list for any proton pump inhibitor before starting
The long-acting injectable is given intramuscularly by health staff

Nursing care

Teach to take it with food
Ask about heartburn medicines, including over-the-counter ones
Watch for depressive symptoms

Pregnancy and breastfeeding

The label describes use in pregnant people already suppressed on rilpivirine; the treating team decides.

Test yourself

Think of the answer, then tap the question to see it.

Why are proton pump inhibitors contraindicated with rilpivirine?

Because rilpivirine needs an acidic stomach to be absorbed; with high pH its levels fall and resistance appears.

Which drug is long-acting injectable rilpivirine combined with?

With injectable cabotegravir.

What structural advantage does rilpivirine have over efavirenz?

It is flexible and adapts to the mutated allosteric pocket, so it keeps activity against some mutations.

Add to my cards (3)

HIV infection and AIDS

← 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: DailyMed - RILPIVIRINE tablet, film coated (DailyMed (U.S. National Library of Medicine), 2026); Rilpivirine: MedlinePlus Drug Information (MedlinePlus (U.S. National Library of Medicine), 2025); ATCDDD - ATC/DDD Index (WHO Collaborating Centre for Drug Statistics Methodology, 2026).

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Representative model, for educational purposes only.