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 C trough 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.