Long-Acting Cabotegravir/Rilpivirine Concentrations in Combination With Intravenous Rifampin: A Case Report

Area of Science:

• Pharmacology and Infectious Diseases
• Clinical Pharmacy and Therapeutics

Background:

• Advancements in antiretroviral therapy (ART) are increasingly focused on long-acting injectable formulations for improved patient adherence and outcomes.
• The potential for drug-drug interactions (DDIs) with long-acting ART is a critical consideration for clinical practice and patient safety.
• Rifampin, a potent inducer of cytochrome P450 enzymes, is frequently used to treat tuberculosis and can interact with numerous medications.

Purpose of the Study:

• To report a real-world case of a significant drug-drug interaction between long-acting injectable cabotegravir/rilpivirine and intravenous rifampin.
• To assess the impact of co-administering rifampin on the plasma concentrations of cabotegravir and rilpivirine.

Main Methods:

• A case report detailing the co-administration of long-acting cabotegravir/rilpivirine with intravenous rifampin in a clinical setting.
• Monitoring of plasma drug concentrations for both cabotegravir and rilpivirine during the concurrent use of rifampin.

Main Results:

• Co-administration of intravenous rifampin with long-acting cabotegravir/rilpivirine led to a substantial decrease in the plasma concentrations of both antiretroviral agents.
• The measured concentrations of cabotegravir and rilpivirine fell below the therapeutic threshold of 4 times the protein-adjusted inhibitory concentration 90 (IC₉₀).
• This indicates a significant pharmacokinetic interaction potentially compromising the virologic efficacy of the antiretroviral regimen.

Conclusions:

• The combination of long-acting cabotegravir/rilpivirine with rifampin poses a risk of sub-therapeutic drug levels.
• Clinicians should exercise caution and consider alternative treatment strategies or intensive therapeutic drug monitoring when these agents are co-administered.
• Further prospective studies are warranted to fully characterize this DDI and establish safe co-administration guidelines.