AIDS dementia complex

January 2007     View PDF     En español

How does HIV cause ADC?

While it is clear that HIV can cause serious nervous system disease, how it causes ADC is unclear. In general, nervous system and mental disorders are caused by the death of nerve cells. While HIV does not directly infect nerve cells, it’s thought that HIV can somehow kill them indirectly.

Macrophages—white cells that are prevalent in the brain and act as large reservoirs for HIV—appear to be HIV’s first target in the central nervous system. HIV-infected macrophages can carry HIV into the brain from the bloodstream. Test tube studies offer these hypotheses about how macrophages may help destroy nerve cells:

• An infected macrophage in the brain may shed a particle on HIV’s outer coat (called gp120), causing damage to nerve cells.
• HIV’s TAT gene, which helps produce new virus, detaches from HIV and circulates in the blood, causing toxic effects in nerve cells.
• The macrophage itself releases a number of substances that, in excess, can be toxic to the brain. Some examples are quinolinic acid and nitric oxide, among an array of other signal molecules. These can bind to nerve cells and cause cell dysfunction or death. Research has found higher levels of quinolinic acid and other markers of cell activation in the CSF of people with ADC.
• HIV infection of other brain cells, including astrocytes.