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Brain viral burden, neuroinflammation and neurodegeneration in HAART-treated HIV positive injecting drug users

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Abstract

The long-term impact of chronic human immunodeficiency virus (HIV) infection on brain status in injecting drug users (IDU) treated with highly active antiretroviral therapy (HAART) is unknown. Viral persistence in the brain with ongoing neuroinflammation may predispose to Alzheimer-like neurodegeneration. In this study, we investigated the brains of ten HAART-treated individuals (six IDU and four non-DU), compared with ten HIV negative controls (six IDU and four non-DU). HIV DNA levels in brain tissue were correlated with plasma and lymphoid tissue viral loads, cognitive status, microglial activation and Tau protein and amyloid deposition. Brain HIV proviral DNA levels were low in most cases but higher in HIV encephalitis (n = 2) and correlated significantly with levels in lymphoid tissue (p = 0.0075), but not with those in plasma. HIV positive subjects expressed more Tau protein and amyloid than HIV negative controls (highest in a 58 year old), as did IDU, but brain viral loads showed no relation to Tau and amyloid. Microglial activation linked significantly to HIV positivity (p = 0.001) and opiate abuse accentuated these microglial changes (p = 0.05). This study confirms that HIV DNA persists in brains despite HAART and that opiate abuse adds to the risk of brain damage in HIV positive subjects. Novel findings in this study show that (1) plasma levels are not a good surrogate indicator of brain status, (2) viral burden in brain and lymphoid tissues is related, and (3) while Tau and amyloid deposition is increased in HIV positive IDU, this is not specifically related to increased HIV burden within the brain.

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Acknowledgments

The Edinburgh HIV Brain Bank is funded by the UK Medical Research Council. We thank the clinicians who looked after these subjects including Drs R Brettle and R Robertson and Professor C Leen, the clinical database manager Alan Wilson, and staff members who have assisted with the investigation of the tissue samples including Frances Carnie and Dr I Anthony. Lastly, this study would not have been possible without the generous trust and support of the donors and their families.

Conflict of interest

All three authors, Dr Donald Smith and Professors Peter Simmonds and Jeanne Bell, declare that they have no conflict of interest with the UK Medical Research Council.

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Authors and Affiliations

  1. Centre for Immunity, Infection and Immunity, Ashworth Laboratories, University of Edinburgh, King’s Buildings, West Mains Road, Edinburgh, EH9 3JT, Scotland, UK

    Donald B. Smith & Peter Simmonds

  2. Neuropathology, University of Edinburgh, Edinburgh, UK

    Jeanne E. Bell

  3. CJD Surveillance Unit, Western General Hospital, Crewe Road, Edinburgh, EH4 2XU, UK

    Jeanne E. Bell

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  1. Donald B. Smith
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  2. Peter Simmonds
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  3. Jeanne E. Bell
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Correspondence to Jeanne E. Bell.

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Smith, D.B., Simmonds, P. & Bell, J.E. Brain viral burden, neuroinflammation and neurodegeneration in HAART-treated HIV positive injecting drug users. J. Neurovirol. 20, 28–38 (2014). https://doi.org/10.1007/s13365-013-0225-3

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