It is widely accepted that infection with HIV is the necessary precondition for the development of AIDS.

It is possible for someone's immune system to be compromised in other ways, and in rare cases, this can lead to same kinds of infections seen in AIDS. When an HIV-negative person experiences immune suppression, there is usually another obvious cause, such as the drugs given after organ transplantation. However, cases where no cause can be identified are termed idiopathic CD4 lymphocytopenia.

Although it is clear that HIV has a central role in the development of AIDS, there remain unanswered questions about some of the specific mechanisms by which it damages the immune system. The human immune system is immensely complex and there are many ways in which it can be affected by a retrovirus such as HIV. Furthermore, it is not clear what role other elements, known as co-factors, may play in the development of immune damage.