The acquired immunodeficiency syndrome (AIDS) is an immunosuppressed state, caused by infection with the human immunodeficiency virus (HIV). It is characterized by opportunistic infections, neoplasms, and neurological manifestations.
According to the United Nations programme on HIV/AIDS (UNAIDS) , it is estimated that in 2008 the HIV pandemic resulted in:
- 33.4 million people living with HIV, of whom 2.1 million were children under 15 years
- 2 million people died from AIDS-related conditions, of whom 430,000 million were children under 15 years
- 2.7 million people became newly infected with HIV
Following infection with HIV, individuals experience a non-specific, flu-like seroconversion illness, manifesting as fever, sore throat, lymphadenopathy, skin rash, and malaise. This is followed by an asymptomatic incubation period, lasting several years.
The diagnosis of AIDS rests on the progression to clinical or serological evidence of immunodeficiency. According to the US CDC definition, one has AIDS if he/she is infected with HIV and presents with either:
- CD4+ T-cell count below 200 cells/µl (or a CD4+ T-cell percentage of total lymphocytes of <14%)
- at least one of the AIDS-defining illnesses
AIDS is caused by HIV, a retrovirus, which infects the CD4+ T-cells and macrophages. Following a period of clinical latency, viral replication within these cells leads to lysis of the CD4+ cells and macrophage-driven transport of the virus into the central nervous system. This results in profound immunosuppression involving primarily the cell-mediated immunity, and in CNS disease, respectively .
The main modes of transmission are sexual contact, via blood (e.g. intravenous drug use or blood transfusions) or vertical transmission to children from HIV-infected mothers during childbirth.
Shortly after the sexual transmission of HIV, it faces its first barrier, the mucosal epithelial cells. The HIV crosses this barrier by processes such as transcytosis, dendritic cells, the complement system, damaged mucosal epithelial cells, etc. Following this transmission, the HIV is free to replicate in the lymphoid tissue resulting in the spread to organs allowing a systematic persistent infection to occur. The main site for this replication is the gut-associated lymphoid tissue (GALT), where there is a vast depletion of CD4+ T cells without being replaced from their differentiation sites . Reasons for this are:
- spread of the HIV-1 to the thymus and/or bone marrow affects the rate of differentiation of T cells and other leukocytes resulting in pan-leukocytopenia
- expression of the homing markers in the GALT is decreased because there is damage to its integrity; the damage results in bacterial translocation which causes a systemic immune activation