The Pathogenesis of HIV-Associated Dementia: Recent Advances Using a SCID Mouse Model of HIV-Encephalitis

In the era of highly active antiretroviral therapy (HAART) there has been a decrease in AIDS death rates and a reduction in HIV-related neurological complications. However, Human Immunodeficiency Virus-1 (HIV)-associated dementia (HAD) still affects at least 7% of HIV-positive individuals. Despite significant advances in HIV research there are still questions surrounding the pathogenesis of HAD. Clinical information and pathological studies suggest that the frontal cortex, basal ganglia, and hippocampus are important neuroanatomical areas involved in HAD. Recent studies utilizing a severe combined immunodeficiency (SCID) mouse model of HIV-encephalitis (HIVE) indicate that central nervous system (CNS) viral load determines the severity of astrogliosis, an important feature of HIVE. Human and animal studies suggest that viral strains may also be important in the pathogenesis of HAD. A recent study suggests that HAART does not eradicate virus in the brain, and therefore, the CNS is a reservoir for HIV. Future research efforts need to focus on the role of viral strain and mutations in the pathogenesis of HAD.