Rapid onset and offset of the interaction between rifampicin and long-acting cabotegravir/rilpivirine: A pharmacokinetic case report.

Long-acting intramuscular cabotegravir/rilpivirine (LA CAB/RPV) is contraindicated with rifampicin because of the risk of markedly reduced antiretroviral exposure, although clinical pharmacokinetic data for this interaction are lacking. We describe a 49-year-old man with virologically suppressed HIV-1 infection receiving LA CAB/RPV every 8 weeks who was treated with rifampicin 600 mg twice daily combined with levofloxacin for 7 days as methicillin-resistant Staphylococcus aureus eradication therapy. Temporary oral bridging therapy with tenofovir disoproxil fumarate/emtricitabine and dolutegravir was started concurrently. Plasma cabotegravir (CAB) and rilpivirine (RPV) concentrations were measured weekly using validated LC-MS/MS. Prior to rifampicin initiation, plasma concentrations were 2.08 mg/L for CAB and 0.126 mg/L for RPV and therefore well above target Ctrough levels of >0.664 mg/L for CAB and >0.032 mg/L for RPV. After 7 days of rifampicin treatment, concentrations decreased to 0.90 mg/L for CAB and 0.022 mg/L for RPV, corresponding to reductions of 57% and 83%, respectively, with RPV concentrations falling below the proposed therapeutic target. One week after rifampicin discontinuation, concentrations recovered to 1.10 mg/L for CAB and 0.050 mg/L for RPV. The concentrations increased further thereafter without additional drug administration, reflecting continued release from the intramuscular depot. HIV-1 RNA remained undetectable throughout follow-up. The observed reduction in RPV exposure exceeded previous physiologically based pharmacokinetic model predictions for intramuscular RPV. This case provides a pharmacokinetic rationale for more nuanced management of short-term enzyme induction in people with HIV receiving LA ART and may help inform future clinical guidance.