Influence of HAART on HIV-related CNS disease and neuroinflammation.
Neuroinflammation has an established link with AIDS-related dementia but has not been investigated in the post-highly active anti-retroviral therapy (HAART) era. In this autopsy study we examined post-HAART cases in Edinburgh for the presence of HIV-related pathology and in well-treated cases for evidence of neuroinflammation. We focused on basal ganglia and the hippocampus, 2 key areas of the brain for cognitive functioning and compared pre- and post-HAART cases for neuroinflammatory status. We find evidence, post-HAART, that there is a high level of microglial/macrophage activation that is comparable with the levels seen, pre-HAART, in HIV encephalitis (HIVE) and AIDS cases. This result was maximal in the hippocampus where microglial/macrophage upregulation in the HAART-treated group exceeded that seen in HIVE. In the basal ganglia, HAART-treated cases showed significantly higher levels of CD68-positive microglia/macrophages than in control brains (p = 0.004), and in the hippocampus levels were significantly higher than those seen in control cases, pre-HAART AIDS, and presymptomatic brains (p = 0.01). However, lymphocyte levels in the areas examined were low in HAART-treated cases. We conclude that there is a surprising degree of ongoing neuroinflammation in HAART-treated patients, particularly in the hippocampus. This may pose a threat for the future health of individuals maintained long-term on HAART therapy.
Anthony
I C
IC
Neuropathology Unit, University of Edinburgh, Alexander Donald Building, Western General Hospital, Edinburgh, Scotland.
Ramage
S N
SN
Carnie
F W
FW
Simmonds
P
P
Bell
J E
JE
D000163:Acquired Immunodeficiency Syndrome / Q000150:complications / Q000188:drug therapy*; D000293:Adolescent; D000328:Adult; D015703:Antigens, CD / Q000378:metabolism; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods*; D001921:Brain / Q000378:metabolism / Q000473:pathology / Q000821:virology; D002493:Central Nervous System Diseases / Q000188:drug therapy* / Q000209:etiology / Q000821:virology*; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D007249:Inflammation / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D019394:Ki-67 Antigen / Q000378:metabolism; D008297:Male; D008875:Middle Aged
D015703:Antigens, CD; D005904:Glial Fibrillary Acidic Protein; D019394:Ki-67 Antigen