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AIDS is the most severe acceleration of infection with HIV. HIV is a retrovirus that primarily infects vital organs of the human immune system such as CD4⁺ T cells (a subset of T cells), macrophages and dendritic cells. It directly and indirectly destroys CD4⁺ T cells.^[8] CD4⁺ T cells are required for the proper functioning of the immune system. When HIV kills CD4⁺ T cells so that there are fewer than 200 CD4⁺ T cells per microliter (µL) of blood, cellular immunity is lost. In some countries, such as the United States, this leads to a diagnosis of AIDS. In other jurisdictions, such as in Canada, AIDS is only diagnosed when a person infected with HIV is diagnosed with one or more of several AIDS-related opportunistic infections or cancers.^[9][10][11] Acute HIV infection progresses over time to clinical latent HIV infection and then to early symptomatic HIV infection and later to AIDS, which is identified either on the basis of the amount of CD4⁺ T cells in the blood, and/or the presence of certain infections, as noted above.

In the absence of antiretroviral therapy, the median time of progression from HIV infection to AIDS is nine to ten years, and the median survival time after developing AIDS is only 9.2 months.^[12] However, the rate of clinical disease progression varies widely between individuals, from two weeks up to 20 years. Many factors affect the rate of progression. These include factors that influence the body's ability to defend against HIV such as the infected person's general immune function.^[13][14] Older people have weaker immune systems, and therefore have a greater risk of rapid disease progression than younger people. Poor access to health care and the existence of coexisting infections such as tuberculosis also may predispose people to faster disease progression.^[12][15][16] The infected person's genetic inheritance plays an important role and some people are resistant to certain strains of HIV. An example of this is people with the CCR5-Δ32 mutation are resistant to infection with certain strains of HIV.^[17] HIV is genetically variable and exists as different strains, which cause different rates of clinical disease progression.^[18][19][20] The use of highly active antiretroviral therapy prolongs both the median time of progression to AIDS and the median survival time.