Over 4 million adults are living with advanced HIV disease with approximately 650 000 fatalities from HIV reported in 2021. People with advanced HIV disease have low immunity and can present to health services in two ways: those who are well but at high risk of developing severe disease, and those who are severely ill. These two groups require specific management approaches that place different demands on the health system. The first group can generally be supported in primary care settings but require differentiated care to meet their needs. The second group are at high risk of death and need focused diagnostics and clinical care, and possibly hospitalisation. Investments in high-quality clinical management of patients with advanced HIV disease who are seriously ill at primary care or hospital level (often only for a brief period of time during their acute illness) improves the likelihood that their condition will stabilise and that they will recover. Providing high-quality and safe clinical care that is accessible to these groups of people living with HIV who are at risk of severe illness and death is a key priority for reaching the global target of zero AIDS deaths.