Rifampicin cut long-acting rilpivirine by 83% in a week, then levels recovered

Design

Pharmacokinetic case report

Population

One man with suppressed HIV-1 on long-acting cabotegravir/rilpivirine every 8 weeks

Primary outcome

Plasma cabotegravir and rilpivirine concentrations during 7 days of rifampicin

Effect

Cabotegravir -57% (to 0.90 mg/L); rilpivirine -83% (to 0.022 mg/L, below 0.032 target)

Long-acting intramuscular cabotegravir and rilpivirine are contraindicated with rifampicin, but measured data on the interaction were lacking. This case report describes a man in his forties with suppressed HIV on injections every eight weeks who needed rifampicin 600 mg twice daily with levofloxacin for seven days to clear MRSA carriage. Oral tenofovir disoproxil, emtricitabine and dolutegravir were started as a bridge at the same time.

Before rifampicin, cabotegravir was 2.08 mg/L and rilpivirine 0.126 mg/L, both well above target troughs. After seven days, cabotegravir had fallen 57% to 0.90 mg/L and rilpivirine 83% to 0.022 mg/L, below its target of 0.032 mg/L. One week after stopping, both were recovering, and they rose further without another injection as the depot kept releasing drug. Viral load stayed undetectable.

The mechanism is induction of CYP3A4, which metabolises both drugs; rilpivirine fell further than physiologically based models had predicted. It is a single case, but it shows that the depot offers no protection against induction, that the effect appears within days, and that a short course with oral cover may be manageable.

• Treat rifampicin as contraindicated with long-acting cabotegravir and rilpivirine unless an HIV specialist plans otherwise.
• If a short rifampicin course is unavoidable, start full oral antiretroviral cover at the same time.
• Measure drug levels where available, and check viral load during and after the course.
• Remember that induction outlasts the last rifampicin dose; plan cover beyond the end of the course.
• Look for a non-rifamycin alternative first; other rifamycins also interact with these drugs.

Why it matters

It shows the depot does not buffer against enzyme induction, and that rilpivirine falls faster than the models predicted.

Don't overread it

One patient with oral cover stayed suppressed; that does not show the combination is safe without it.

The statistics, in plain English

These are measurements from one patient. They show what can happen, not how often, and another patient's levels could fall more or less.

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