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Lookup NU author(s): Carla Roca Bayerri, Dr Fiona Robertson, Dr Angela Pyle, Professor Gavin Hudson, Dr Brendan PayneORCiD
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America.BACKGROUND: Neurocognitive impairment (NCI) remains common in people living with human immunodeficiency virus (PLWH), despite suppressive antiretroviral therapy (ART), but the reasons remain incompletely understood. Mitochondrial dysfunction is a hallmark of aging and of neurodegenerative diseases. We hypothesized that human immunodeficiency virus (HIV) or ART may lead to mitochondrial abnormalities in the brain, thus contributing to NCI. METHODS: We studied postmortem frozen brain samples from 52 PLWH and 40 HIV-negative controls. Cellular mitochondrial DNA (mtDNA) content and levels of large-scale mtDNA deletions were measured by real-time polymerase chain reaction. Heteroplasmic mtDNA point mutations were quantified by deep sequencing (Illumina). Neurocognitive data were taken within 48 months antemortem. RESULTS: We observed a decrease in mtDNA content, an increase in the mtDNA "common deletion," and an increase in mtDNA point mutations with age (all P < .05). Each of these changes was exacerbated in HIV-positive cases compared with HIV-negative controls (all P < .05). ART exposures, including nucleoside analogue reverse transcriptase inhibitors, were not associated with changes in mtDNA. The number of mtDNA point mutations was associated with low CD4/CD8 ratio (P = .04) and with NCI (global T-score, P = .007). CONCLUSIONS: In people with predominantly advanced HIV infection, there is exacerbation of age-associated mtDNA damage. This change is driven by HIV per se rather than by ART toxicity and may contribute to NCI. These data suggest that mitochondrial dysfunction may be a mediator of adverse aging phenotypes in PLWH.
Author(s): Roca-Bayerri C, Robertson F, Pyle A, Hudson G, Payne BAI
Publication type: Article
Publication status: Published
Journal: Clinical Infectious Diseases
Year: 2021
Volume: 73
Issue: 2
Pages: e466-e473
Print publication date: 15/07/2021
Online publication date: 28/07/2021
Acceptance date: 14/07/2021
Date deposited: 25/08/2021
ISSN (print): 1058-4838
ISSN (electronic): 1537-6591
Publisher: Oxford University Press
URL: https://doi.org/10.1093/cid/ciaa984
DOI: 10.1093/cid/ciaa984
PubMed id: 32722761
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