Rifampicin cut rilpivirine levels from long-acting injections by 83% in a week, and they recovered as quickly

Design

Pharmacokinetic case report with weekly LC-MS/MS levels

Population

One man with suppressed HIV on 8-weekly long-acting cabotegravir-rilpivirine, given rifampicin for 7 days

Primary outcome

Plasma cabotegravir and rilpivirine concentrations

Effect

Cabotegravir −57% (2.08→0.90 mg/L); rilpivirine −83% (0.126→0.022 mg/L); recovery within 1 week

Long-acting intramuscular cabotegravir-rilpivirine is contraindicated with rifampicin, but how fast and how far levels fall had not been measured in a patient. This case report describes a man in his forties with suppressed HIV on injections every 8 weeks who needed seven days of rifampicin 600 mg twice daily with levofloxacin for MRSA eradication. Oral tenofovir-emtricitabine with dolutegravir was given as a bridge, and plasma levels were measured weekly.

After seven days of rifampicin, cabotegravir fell from 2.08 to 0.90 mg/L (57%) and rilpivirine from 0.126 to 0.022 mg/L (83%), the latter below its proposed target trough of 0.032 mg/L. A week after rifampicin stopped, levels had partly recovered (1.10 and 0.050 mg/L) and went on rising without a further dose, as the depot kept releasing drug. Viral load stayed undetectable.

This is one patient, and the bridging regimen protected him. The useful lesson is about time course: induction by rifampicin took hold within a week and wore off within a week or two, and the fall in rilpivirine was larger than modelling had predicted. That supports covering short rifampicin courses with oral bridging rather than abandoning long-acting therapy, but it is not a basis for new guidance on its own.

• Rifampicin remains contraindicated with long-acting cabotegravir-rilpivirine without additional cover.
• If a short rifampicin course is unavoidable, give a fully active oral regimen as a bridge and seek HIV pharmacology advice.
• Rilpivirine fell further than cabotegravir and below target within seven days.
• Levels recovered within about a week of stopping rifampicin, without an extra injection.
• Measure drug levels where available when an inducer is given to someone on long-acting therapy.

Why it matters

It gives the first measured time course for an interaction that until now was managed on predictions.

Don't overread it

A single case with bridging therapy cannot show that long-acting therapy is safe to continue through rifampicin.

The statistics, in plain English

These are serial measurements in one patient, so they show what can happen, not how often or by how much in others. The rilpivirine fall exceeding model predictions is a reason to be cautious about relying on models for this interaction.

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