It is a syndrome of progressive deterioration of memory, cognition, behavior, and motor function in HIV-infected individuals during the late stages of the disease, when immunodeficiency is severe.
HIV-associated neurocognitive disorders are associated with a metabolic encephalopathy induced by HIV infection and fueled by immune activation of macrophages and microglia.
The essential features of HIV-associated dementia (HAD) are disabling cognitive impairment accompanied by motor dysfunction, speech problems and behavioral change.
Histopathologically, it is identified by the infiltration of monocytes and macrophages into the central nervous system (CNS), gliosis, pallor of myelin sheaths, abnormalities of dendritic processes and neuronal loss.
[2][4] HAD typically occurs after years of HIV infection and is associated with low CD4+ T cell levels and high plasma viral loads.
[6][7] With the advent of highly active antiretroviral therapy (HAART), the incidence of HAD has declined in developed countries, although its prevalence is increasing.
[16] In advanced cases of HIV-associated dementia, speech delay, motor dysfunction, and impaired thought and behavior are observed.
The infected macrophages and microglia also appear to produce additional factors such as chemokines and cytokines that can affect neurons as well as other brain cells known as astrocytes.
[19] In the neuronal cells, the HIV gp120 induces mitochondrial-death proteins like caspases, which may influence the upregulation of the death receptor Fas leading to apoptosis.
[23] HIV is associated with pathological changes in mainly subcortical and fronto-striatal areas of the brain, including the basal ganglia, deep white matter, and hippocampal regions.
[24] A recent longitudinal study of a small representative cohort of HIV-positive patients on stable medication regiments suggests that this cortical atrophy is progressive, and is in part related to nadir CD4.
[28] Changes in the brain may be ongoing but asymptomatic, that is with minimal interference in functioning, making it difficult to diagnose HIV-associated neurocognitive disorders in the early stages.
This dysfunction with the basal ganglia and PFC may explain the executive function and semantic event sequencing task impairments noted in HIV+ patients included in this study.
Additionally, the anterior parietal activity showed a relationship with caudate functioning, which implicates a compensatory mechanism set forth when damage to the fronto-striatal system occurs.
[14] In identification tasks, administered by Clark et al. (2010), HIV+ patients and control participants were asked to identify different facial emotions and landscapes, with these picture categories matched for image complexity.
[14] Mother-to-child transmission during pregnancy is the dominant mode of acquisition of HIV infection in children and has been associated with an increased risk of mortality and developmental delay.
By regulating the survival, differentiation and maintenance of specific functions of neuronal and glial precursors, these extracellular signals can influence many steps of the CNS development and concur in controlling virus-cell interactions in the maturing brain.
[33] In addition to the production of cytokines, HIV-1 infected mononuclear cells and astrocytes can produce a number of soluble mediators, including viral proteins such as gp120 and Tat, that can exert damaging effects on both developing and mature neural tissues.
Thus, it is likely that a complex interaction of several mediators may alter the function and survival of actively developing and maturing cells, responsible for the neurologic disorders.