HIV-associated neurocognitive disorders (HAND) describes different levels of neurocognitive impairment,
which are a common complication of HIV infection. The most severe of these, HIV-associated dementia (HIV-D), has
decreased in incidence since the introduction of combination antiretroviral therapy (cART), while an increase in the less
severe, minor neurocognitive disorder (MND), is now seen. The neuropathogenesis of HAND is not completely
understood, however macrophages (MΦ)s/microglia are believed to play a prominent role in the development of the more
severe HIV-D. Here, we report evidence of neuroinflammation in autopsy tissues from patients with HIV infection and
varying degrees of neurocognitive impairment but without HIV encephalitis (HIVE). MΦ/microglial and astrocyte
activation is less intense but similar to that seen in HIVE, one of the neuropathologies underlying HIV-D. MΦs and
microglia appear to be activated, as determined by CD163, CD16, and HLA-DR expression, many having a rounded or
ramified morphology with thickened processes, classically associated with activation. Astrocytes also show considerable
morphological alterations consistent with an activated state and have increased expression of GFAP and vimentin, as
compared to seronegative controls. Interestingly, in some areas, astrocyte activation appears to be limited to perivascular
locations, suggesting events at the blood-brain barrier may influence astrocyte activity. In contrast to HIVE, productive
HIV infection was not detectable by tyramide signal-amplified immunohistochemistry or in situ hybridization in the CNS
of HIV infected persons without encephalitis. These findings suggest significant CNS inflammation, even in the absence
of detectable virus production, is a common mechanism between the lesser and more severe HIV-associated
neurodegenerative disease processes and supports the notion that MND and HIV-D are a continuum of the same disease.
CD16, CD163, HAND, HIV, macrophage, microglia, neuroinflammation, neuropathogenesis.
Department of Neuroscience, Temple University School of Medicine, MERB, Room 748, Philadelphia, PA 19140, USA.