Off-label use of antiretroviral drugs: ethical and legal implications for clinical decision-making

The use of authorized medicinal products under conditions other than those approved, commonly referred to as off-label use, is an increasingly frequent practice in health care. It is particularly relevant in the therapeutic management of human immunodeficiency virus infection, where treatment innovation often outpaces regulatory updates. In the absence of specific protocols to guide the appropriateness of off-label prescribing, this narrative review analyses, from an ethical and legal perspective, the conditions under which off-label use may be considered an appropriate therapeutic option. To this end, we examine the clinical foundations of off-label use, including the quality and certainty of the available scientific evidence and its impact on the benefit-risk and cost-benefit balance, the exceptional nature of its use, and the application of decisionmaking algorithms to guide prescribing. We also identify the main ethical dilemmas associated with off-label use from principlist, virtue-based, and utilitarian bioethical perspectives, as well as the principal conflicts of interest among the different stakeholders involved in the off-label use of antiretroviral drugs. Finally, we propose strategies aimed at promoting a more prudent, equitable, and transparent use of off-label medicines, strengthening responsible, patient-centered decision-making.