What is the significance of the pharmacokinetic profile and potential drug-drug interactions of long-acting intramuscular cabotegravir and rilpivirine?

Antiretroviral treatments have greatly improved over the years from complex regimens with a high pill burden, multiple daily dosing, and considerable toxicities to highly effective daily single-pill regimens with good tolerability. Another outstanding milestone has been reached with the approval of the first long-acting (LA) intramuscular treatment combining cabotegravir and rilpivirine. After an optional oral lead-in phase, followed by an intramuscular loading dose (cabotegravir/rilpivirine 600/900 mg), cabotegravir/rilpivirine is administered intramuscularly at a maintenance dose of 400/600 mg every 4 weeks or 600/900 mg every 8 weeks [1–3]. Thus, by eliminating the need for daily administration, LA injectable antiretrovirals may improve adherence. Other advantages include the possibility of treating people with swallowing difficulties and the prevention of drug–drug interactions (DDIs) occurring at the gastrointestinal level. The slow release of cabotegravir/ rilpivirine from the muscle combined with the avoidance of the first-pass metabolism will have an impact on the magnitude of DDIs. This editorial provides insight into the intramuscular administration of cabotegravir/rilpivirine, presents available DDI data, and discusses how to interpret and manage DDIs after intramuscular administration.