Despite the challenges to the HIV response in the Asia-Pacific, a demedicalisation of HIV intervention has been demonstrated to be an important strategy to maximise the uptake of HIV prevention tools among key populations in this region. Demedicalisation of HIV interventions translates medical discourse and shifts the paradigm from a disease-focused to a people-centred approach. It also recognises real-life experiences of key populations in the HIV response by empowering them to voice their needs and be at the forefront of the epidemic control. We further categorise a demedicalisation approach into three frameworks: (1) the demystification of clinical or medical concerns; (2) the destigmatisation of people living with HIV; and (3) the decentralisation of healthcare services. This article reviewed the demedicalisation framework by looking at the HIV intervention examples from countries in the Asia-Pacific, which included: (1) a study on drug-drug interaction between pre-exposure prophylaxis and feminising hormone treatment for transgender women; (2) the roles of key population-led health services; and (3) certification of key population lay providers.