Acquired immunodeficiency syndrome (AIDS) is an important public health problem in China. In 2005, the first edition of the guidelines for the diagnosis and treatment of AIDS was formulated by the AIDS Professional Group of Society of Infectious Diseases of Chinese Medical Association, which was updated in 2011, 2015, and 2018, respectively. The 2021 edition of the guidelines has been revised based on the fourth edition and updated according to the national clinical practice and the latest research findings on opportunistic infections, antiretroviral therapy, post-exposure prophylaxis, pre-exposure prophylaxis (PrEP), whole-course management of human immunodeficiency virus infections, and prevention of mother to child transmission. The 2021 edition also introduces in detail the indications, medication regimen, follow-up and monitoring, and precautions for PrEP. This guide will be updated regularly according to the latest clinical evidence.