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Current HIV Research
ISSN (Print): 1570-162X
ISSN (Online): 1873-4251
Epub Full Text Article
DOI: 10.2174/1570162X12666140526114956      Price:  $95

Brain Inflammation is a Common Feature of HIV-Infected Patients Without HIV Encephalitis or Productive Brain Infection

Author(s): Eleonora Tavazzi, David Morrison, Peter Sullivan, Susan Morgello and Tracy Fischer
HIV-associated neurocognitive disorders (HAND) describes different levels of neurocognitive impairment,whichare 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), whilean increase inthe less severe, minor neurocognitive disorder (MND), is now seen. The neuropathogenesis of HAND is not completely understood,however macrophages (M)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). M/microglialand astrocyte activation is less intensebut similar tothat seen in HIVE, one of the neuropathologiesunderlyingHIV-D. Ms and microglia appear to be activated, as determined by CD163, CD16and HLA-DR expression, many having a rounded or ramified morphology with thickened processes, classicallyassociated 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, isa 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 process
Graphical Abstract:
CD16, CD163, HAND, HIV, macrophage, microglia, neuroinflammation, neuropathogenesis
Department of Neuroscience Temple University School of Medicine MERB, Room 748 Philadelphia, PA 19140