Neuroinflammation in treated HIV-positive individuals: A TSPO PET study
File(s)
Published version
Author(s)
Type
Journal Article
Abstract
OBJECTIVE: To explore the effects of microglial activation on brain function and structure, and its relationship with peripheral inflammatory markers, in treated, HIV-positive individuals, using in vivo [(11)C]PBR28 PET (to measure the 18 kDa translocator protein [TSPO]). METHODS: Cognitively healthy HIV-positive individuals on suppressive antiretroviral therapy and HIV-negative individuals (controls) underwent brain [(11)C]PBR28 PET and MRI. HIV-positive patients completed neuropsychological testing and CSF testing for chemokines. The concentration of bacterial ribosomal 16sDNA in plasma was measured as a marker of microbial translocation. RESULTS: HIV-positive individuals showed global increases in TSPO expression compared to controls (corrected p < 0.01), with significant regional increases in the parietal (p = 0.001) and occipital (p = 0.046) lobes and in the globus pallidus (p = 0.035). TSPO binding in the hippocampus, amygdala, and thalamus were associated with poorer global cognitive performance in tasks assessing verbal and visual memory (p < 0.05). Increased TSPO binding was associated with increased brain white matter diffusion MRI mean diffusivity in HIV-positive individuals, a lower CD4/CD8 ratio, and both high pretreatment HIV RNA and plasma concentration ribosomal 16s DNA (p < 0.05). CONCLUSIONS: Cognitively healthy HIV-positive individuals show evidence for a chronically activated brain innate immune response and elevated blood markers of microbial translocation despite effective control of plasma viremia. Increased brain inflammation is associated with poorer cognitive performance and white matter microstructural pathology, suggesting a possible role in cognitive impairments found in some HIV-positive patients despite effective treatment.
Date Issued
2016-04-12
Date Acceptance
2015-01-06
Citation
Neurology, 2016, 86 (15), pp.1425-1432
ISSN
1526-632X
Publisher
American Academy of Neurology
Start Page
1425
End Page
1432
Journal / Book Title
Neurology
Volume
86
Issue
15
Copyright Statement
© 2016 American Academy of Neurology
Sponsor
Medical Research Council (MRC)
Medical Research Council (MRC)
Identifier
PII: WNL.0000000000002485
Grant Number
G0900897
MR/N026934/1
Subjects
Science & Technology
Life Sciences & Biomedicine
Clinical Neurology
Neurosciences & Neurology
POSITRON-EMISSION-TOMOGRAPHY
PERIPHERAL BENZODIAZEPINE-RECEPTOR
ACTIVE ANTIRETROVIRAL THERAPY
PROTEIN 18 KDA
CEREBROSPINAL-FLUID
IN-VIVO
MICROBIAL TRANSLOCATION
MULTIPLE-SCLEROSIS
IMMUNE ACTIVATION
INFECTED SUBJECTS
Acetamides
Adult
Anti-Retroviral Agents
Biomarkers
Brain
Brain Mapping
CD4-CD8 Ratio
Carbon Radioisotopes
Chemokines
DNA, Bacterial
DNA, Ribosomal
Diffusion Tensor Imaging
HIV Infections
Humans
Male
Neuropsychological Tests
Positron Emission Tomography Computed Tomography
Pyridines
RNA, Viral
Radiopharmaceuticals
Receptors, GABA
White Matter
Brain
Humans
HIV Infections
Carbon Radioisotopes
Acetamides
Pyridines
Receptors, GABA
DNA, Bacterial
DNA, Ribosomal
RNA, Viral
Chemokines
Anti-Retroviral Agents
Radiopharmaceuticals
CD4-CD8 Ratio
Brain Mapping
Neuropsychological Tests
Adult
Male
Diffusion Tensor Imaging
White Matter
Biomarkers
Positron Emission Tomography Computed Tomography
Neurology & Neurosurgery
1103 Clinical Sciences
1109 Neurosciences
1702 Cognitive Sciences
Publication Status
Published
Date Publish Online
2016-02-24