Pharmacokinetics and Pharmacodynamics of Cabotegravir, a Long-Acting HIV Integrase Strand Transfer Inhibitor

Available antiretroviral drugs have demonstrated effectiveness in both pre-exposure prophylaxis and treatment of HIV infection. However, some concerns still persist regarding these therapies, mainly related to patient adherence, drug toxicity and dosing convenience. Cabotegravir is a potent integrase strand transfer inhibitor with a chemical structure similar to dolutegravir that is under clinical evaluation both as oral and long-acting injectable (LAI) formulations for both the prevention or treatment of HIV infection. Indeed, preclinical and clinical studies have consistently shown that LAI cabotegravir is readily absorbed following intramuscular and subcutaneous administration, with an elimination half-life of approximately 40 days, permitting infrequent dosing, possibly once every 1 or 2 months (eventually combined with rilpivirine). Here, we reviewed the existing literature on the preclinical and clinical pharmacokinetics and pharmacodynamics of LAI cabotegravir, with emphasis on the actual pharmacokinetic challenges of this novel formulation, as well as its potential to act as a victim or perpetrator of drug–drug interactions.