In untreated people, the average loss of CD4 T-cells in blood is about 60 cells/mm³ per year but there is a wide range in this change among different people. Loss of CD4 T-cells and the direct and indirect abnormalities caused by this mainly affect acquired immunity and cell-mediated responses. Newly encountered antigens will not cause much of an immune response, and loss of memory T-cells will take away the increased efficiency in responding to antigens encountered more than once. This type of immune deficiency makes people more susceptible to disease from viruses, intracellular bacteria, fungi and some protozoa.

Humoral immunity (using B-cells) will not be so badly affected if memory cells for recognising common antigens exist. Most adults have a large population of B-cells which are good at responding to common bacteria that the body has seen before. Children do not have such good immune memory and in HIV infection children have problems with a wider range of bacteria than adults. Lack of proper cytokine release also affects the action of most immune cells including the phagocytic cells: macrophages and neutrophils.

In progressive immune deficiency a group of relatively minor conditions called AIDS-related complex (ARC) generally appears which can feature problems with weight loss, non-specific diarrhoea, oral fungal infection (Candida or thrush) and various skin conditions. AIDS is a more serious group of potentially life-threatening secondary infections and two types of cancers, both of which may be caused by viral infections. The manifestations of AIDS depend on the type of infection and which part of the body is affected. Many of these conditions respond to medical treatment. Some, such as Pneumocystis pneumonia, may resolve but can reappear later on.