The Centers for Disease Control and Prevention (CDC) in the United States have constructed a series of case definitions for AIDS. These have evolved over time as the shape of the epidemic changes.

The CDC definition of AIDS was modified in August 1985 to include specific reference to HIV. It was also revised in 1987 to include a broader range of specific diseases. Since the beginning of 1993 a new CDC definition has been used, which means that an HIV-positive person may now be diagnosed as having AIDS if he or she develops pulmonary tuberculosis, invasive cervical cancer or recurrent bacterial pneumonia, or a CD4 cell count of less than 200 cells/mm³.

European countries have also incorporated the three new clinical conditions into their AIDS definitions, but they do not use a CD4 cell count below 200 cells/mm³ as part of the definition.

The CDC has a specific definition for the classification of HIV disease in children.

The CDC definitions are of little use in Africa and other less developed areas, where the marked differences in environment result in a completely different clinical picture, and the absence of high technology laboratories means that some infections such as cytomegalovirus and Mycobacterium avium intracellulare would be very difficult to diagnose. To try to redress these issues, the World Health Organization has developed special definitions for adults and children in Africa.

Because a number of clinical trials in the United Kingdom still use the pre-1993 CDC definition to define who is eligible to take part, we have kept a summary of that definition alongside a description of the current definition in this section.