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Risk Factors and Pathogenesis of HIV-Associated Neurocognitive Disorder: The Role of Host Genetics

1
Division of Physiological Sciences, Department of Human Biology, Faculty of Health Sciences, University of Cape Town, Observatory 7925, South Africa
2
EuroEspes Biomedical Research Center, Institute of Medical Science and Genomic Medicine, 15165 Bergondo, Corunna, Spain
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2018, 19(11), 3594; https://doi.org/10.3390/ijms19113594
Received: 23 October 2018 / Revised: 12 November 2018 / Accepted: 12 November 2018 / Published: 14 November 2018
(This article belongs to the Special Issue Genomics of Brain Disorders)
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Abstract

Neurocognitive impairments associated with human immunodeficiency virus (HIV) infection remain a considerable health issue for almost half the people living with HIV, despite progress in HIV treatment through combination antiretroviral therapy (cART). The pathogenesis and risk factors of HIV-associated neurocognitive disorder (HAND) are still incompletely understood. This is partly due to the complexity of HAND diagnostics, as phenotypes present with high variability and change over time. Our current understanding is that HIV enters the central nervous system (CNS) during infection, persisting and replicating in resident immune and supporting cells, with the subsequent host immune response and inflammation likely adding to the development of HAND. Differences in host (human) genetics determine, in part, the effectiveness of the immune response and other factors that increase the vulnerability to HAND. This review describes findings from studies investigating the role of human host genetics in the pathogenesis of HAND, including potential risk factors for developing HAND. The similarities and differences between HAND and Alzheimer’s disease are also discussed. While some specific variations in host genes regulating immune responses and neurotransmission have been associated with protection or risk of HAND development, the effects are generally small and findings poorly replicated. Nevertheless, a few specific gene variants appear to affect the risk for developing HAND and aid our understanding of HAND pathogenesis. View Full-Text
Keywords: HIV-associated neurocognitive disorders; HIV-associated dementia; HIV-encephalitis; neuroAIDS; host genetics; risk factors; HIV; cognitive impairment; polymorphisms HIV-associated neurocognitive disorders; HIV-associated dementia; HIV-encephalitis; neuroAIDS; host genetics; risk factors; HIV; cognitive impairment; polymorphisms
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Olivier, I.S.; Cacabelos, R.; Naidoo, V. Risk Factors and Pathogenesis of HIV-Associated Neurocognitive Disorder: The Role of Host Genetics. Int. J. Mol. Sci. 2018, 19, 3594.

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