Neuroimaging abnormalities in clade C HIV are independent of Tat genetic diversity.

Abstract:

:Controversy remains regarding the neurotoxicity of clade C human immunodeficiency virus (HIV-C). When examined in preclinical studies, a cysteine to serine substitution in the C31 dicysteine motif of the HIV-C Tat protein (C31S) results in less severe brain injury compared to other viral clades. By contrast, patient cohort studies identify significant neuropsychological impairment among HIV-C individuals independent of Tat variability. The present study clarified this discrepancy by examining neuroimaging markers of brain integrity among HIV-C individuals with and without the Tat substitution. Thirty-seven HIV-C individuals with the Tat C31S substitution, 109 HIV-C individuals without the Tat substitution (C31C), and 34 HIV- controls underwent 3T structural magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI). Volumes were determined for the caudate, putamen, thalamus, corpus callosum, total gray matter, and total white matter. DTI metrics included fractional anisotropy (FA), radial diffusivity (RD), and axial diffusivity (AD). Tracts of interest included the anterior thalamic radiation (ATR), cingulum bundle (CING), uncinate fasciculus (UNC), and corpus callosum (CC). HIV+ individuals exhibited smaller volumes in subcortical gray matter, total gray matter and total white matter compared to HIV- controls. HIV+ individuals also exhibited DTI abnormalities across multiple tracts compared to HIV- controls. By contrast, neither volumetric nor diffusion indices differed significantly between the Tat C31S and C31C groups. Tat C31S status is not a sufficient biomarker of HIV-related brain integrity in patient populations. Clinical attention directed at brain health is warranted for all HIV+ individuals, independent of Tat C31S or clade C status.

journal_name

J Neurovirol

journal_title

Journal of neurovirology

authors

Paul RH,Phillips S,Hoare J,Laidlaw DH,Cabeen R,Olbricht GR,Su Y,Stein DJ,Engelbrecht S,Seedat S,Salminen LE,Baker LM,Heaps J,Joska J

doi

10.1007/s13365-016-0503-y

subject

Has Abstract

pub_date

2017-04-01 00:00:00

pages

319-328

issue

2

eissn

1355-0284

issn

1538-2443

pii

10.1007/s13365-016-0503-y

journal_volume

23

pub_type

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