An ultra-long-acting formulation of cabotegravir may offer an HIV pre-exposure prophylaxis (PrEP) and treatment option that could be administered three times a year. The approved formulation of cabotegravir for PrEP (Apretude) is administered by a health care provider every other month, while cabotegravir plus rilpivirine (Cabenuva) for treatment is given monthly or every other month. In a Phase I trial, the new formulation—dubbed CAB-ULA— given by subcutaneous or intramuscular injection achieved comparable drug exposure levels but lasted longer in the body. Its pharmacokinetic profiles were flatter, indicating slower absorption. Pharmacokinetic modeling predicted that intramuscular CAB-ULA given at least four months apart would achieve higher drug exposure than the current formulation given every two months. CAB-ULA was generally well tolerated. Intramuscular CAB-ULA will now progress to late-stage trials, and more testing of the subcutaneous formulation—which could potentially be self-administered—is planned.