{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T00:35:33Z","timestamp":1787963733266,"version":"build-2784847793"},"reference-count":34,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2020,7,28]],"date-time":"2020-07-28T00:00:00Z","timestamp":1595894400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Wellcome Centre for Mitochondrial Research","award":["109975\/Z\/15\/Z, 203105\/Z\/16\/Z"],"award-info":[{"award-number":["109975\/Z\/15\/Z, 203105\/Z\/16\/Z"]}]},{"name":"National Institute of Mental Health and the National Institute of Neurological Disorders and Stroke"},{"name":"Manhattan HIV Brain Bank","award":["U24MH100931"],"award-info":[{"award-number":["U24MH100931"]}]},{"name":"Texas NeuroAIDS Research Center","award":["U24MH100930"],"award-info":[{"award-number":["U24MH100930"]}]},{"name":"National Neurological AIDS Bank","award":["U24MH100929"],"award-info":[{"award-number":["U24MH100929"]}]},{"name":"California NeuroAIDS Tissue network","award":["U24MH100928"],"award-info":[{"award-number":["U24MH100928"]}]},{"name":"Data Coordinating Center","award":["U24MH100925"],"award-info":[{"award-number":["U24MH100925"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,7,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We observed a decrease in mtDNA content, an increase in the mtDNA \u201ccommon deletion,\u201d and an increase in mtDNA point mutations with age (all P\u2005&amp;lt;\u2005.05). Each of these changes was exacerbated in HIV-positive cases compared with HIV-negative controls (all P\u2005&amp;lt;\u2005.05). 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).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/cid\/ciaa984","type":"journal-article","created":{"date-parts":[[2020,7,14]],"date-time":"2020-07-14T15:08:57Z","timestamp":1594739337000},"page":"e466-e473","source":"Crossref","is-referenced-by-count":36,"title":["Mitochondrial DNA Damage and Brain Aging in Human Immunodeficiency Virus"],"prefix":"10.1093","volume":"73","author":[{"given":"Carla","family":"Roca-Bayerri","sequence":"first","affiliation":[{"name":"Wellcome Centre for Mitochondrial Research, Translational and Clinical Research Institute, Newcastle University, Newcastle-upon-Tyne, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fiona","family":"Robertson","sequence":"additional","affiliation":[{"name":"Wellcome Centre for Mitochondrial Research, Translational and Clinical Research Institute, Newcastle University, 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