In this article, we first present the current administration criteria, the risk factors for virological failure, and our practical experience with the first long-acting injectable HIV treatment available in Switzerland (the combination of cabotegravir/rilpivirine). We then discuss the theoretical and practical potential, as illustrated by an innovative study in San Francisco, provided by administering long-acting treatment outside the current criteria. This approach could notably offer antiretroviral treatment to particularly vulnerable populations for whom oral antiretroviral therapy is sometimes challenging. Finally, we touch upon the future drug prospects of long-acting treatments under study for HIV.