Brain inflammation is a common feature of HIV-infected patients without HIV encephalitis or productive brain infection.

TitleBrain inflammation is a common feature of HIV-infected patients without HIV encephalitis or productive brain infection.
Publication TypeJournal Article
Year of Publication2014
AuthorsTavazzi, E, Morrison, D, Sullivan, P, Morgello, S, Fischer, T
JournalCurr HIV Res
Date Published2014
KeywordsAntigens, CD, Antigens, Differentiation, Myelomonocytic, Brain, Encephalitis, External, HIV Infections, Humans, Macrophages, Microglia, Receptors, Cell Surface, Receptors, IgG

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.

Alternate JournalCurr HIV Res
PubMed ID24862332
PubMed Central IDPMC4152918
Grant ListR01 NS063605 / NS / NINDS NIH HHS / United States
U24 MH100931 / MH / NIMH NIH HHS / United States