{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T14:26:20Z","timestamp":1780496780351,"version":"3.54.1"},"reference-count":38,"publisher":"Springer Science and Business Media LLC","issue":"2","license":[{"start":{"date-parts":[[2021,2,7]],"date-time":"2021-02-07T00:00:00Z","timestamp":1612656000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springer.com\/tdm"},{"start":{"date-parts":[[2021,2,7]],"date-time":"2021-02-07T00:00:00Z","timestamp":1612656000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J. Neurovirol."],"published-print":{"date-parts":[[2022,4]]},"DOI":"10.1007\/s13365-021-00947-3","type":"journal-article","created":{"date-parts":[[2021,2,9]],"date-time":"2021-02-09T05:03:09Z","timestamp":1612846989000},"page":"208-216","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Accelerated epigenetic aging in adolescents living with HIV is associated with altered development of brain structures"],"prefix":"10.1007","volume":"28","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6963-3557","authenticated-orcid":false,"given":"Jacqueline","family":"Hoare","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan J.","family":"Stein","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah J.","family":"Heany","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Paul","family":"Fouche","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole","family":"Phillips","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sebnem","family":"Er","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Landon","family":"Myer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heather J.","family":"Zar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steve","family":"Horvath","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew J.","family":"Levine","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,2,7]]},"reference":[{"key":"947_CR1","doi-asserted-by":"publisher","first-page":"2363","DOI":"10.3174\/ajnr.A4921","volume":"37","author":"C Ackermann","year":"2016","unstructured":"Ackermann C, Andronikou S, Saleh MG et al (2016) Early antiretroviral therapy in HIV-infected children is associated with diffuse white matter structural abnormality and corpus callosum sparing. Am J Neuroradiol 37:2363\u20132369. https:\/\/doi.org\/10.3174\/ajnr.A4921","journal-title":"Am J Neuroradiol"},{"key":"947_CR2","doi-asserted-by":"publisher","first-page":"689","DOI":"10.2217\/epi-2016-0179","volume":"9","author":"NJ Armstrong","year":"2017","unstructured":"Armstrong NJ, Mather KA, Thalamuthu A et al (2017) Aging, exceptional longevity and comparisons of the Hannum and Horvath epigenetic clocks. Epigenomics 9:689\u2013700. https:\/\/doi.org\/10.2217\/epi-2016-0179","journal-title":"Epigenomics"},{"key":"947_CR3","doi-asserted-by":"publisher","first-page":"1363","DOI":"10.1093\/bioinformatics\/btu049","volume":"30","author":"MJ Aryee","year":"2014","unstructured":"Aryee MJ, Jaffe AE, Corrada-Bravo H et al (2014) Minfi: a flexible and comprehensive Bioconductor package for the analysis of Infinium DNA methylation microarrays. Bioinformatics 30:1363\u20131369. https:\/\/doi.org\/10.1093\/bioinformatics\/btu049","journal-title":"Bioinformatics"},{"key":"947_CR4","doi-asserted-by":"publisher","first-page":"1186","DOI":"10.1186\/s13148-016-0186-5","volume":"8","author":"LP Breitling","year":"2016","unstructured":"Breitling LP, Saum K-U, Perna L et al (2016) Frailty is associated with the epigenetic clock but not with telomere length in a German cohort. Clin Epigenetics 8:1186. https:\/\/doi.org\/10.1186\/s13148-016-0186-5","journal-title":"Clin Epigenetics"},{"key":"947_CR5","doi-asserted-by":"publisher","first-page":"699","DOI":"10.1007\/s13365-016-0467-y","volume":"22","author":"S Buch","year":"2016","unstructured":"Buch S, Chivero ET, Hoare J et al (2016) Proceedings from the NIMH symposium on \u201cNeuroAIDS in Africa: neurological and neuropsychiatric complications of HIV.\u201d J Neurovirol 22:699\u2013702. https:\/\/doi.org\/10.1007\/s13365-016-0467-y","journal-title":"J Neurovirol"},{"key":"947_CR6","doi-asserted-by":"publisher","first-page":"1844","DOI":"10.18632\/aging.101020","volume":"8","author":"BH Chen","year":"2016","unstructured":"Chen BH, Marioni RE, Colicino E et al (2016) DNA methylation-based measures of biological age: meta-analysis predicting time to death. Aging (Albany NY) 8:1844\u20131865. https:\/\/doi.org\/10.18632\/aging.101020","journal-title":"Aging (Albany NY)"},{"key":"947_CR7","doi-asserted-by":"publisher","first-page":"585","DOI":"10.2217\/epi-2017-0132","volume":"10","author":"L Chouliaras","year":"2018","unstructured":"Chouliaras L, Pishva E, Haapakoski R et al (2018) Peripheral DNA methylation, cognitive decline and brain aging: pilot findings from the Whitehall II imaging study. Epigenomics 10:585\u2013595. https:\/\/doi.org\/10.2217\/epi-2017-0132","journal-title":"Epigenomics"},{"key":"947_CR8","doi-asserted-by":"publisher","first-page":"149","DOI":"10.1111\/acel.12421","volume":"15","author":"L Christiansen","year":"2015","unstructured":"Christiansen L, Lenart A, Tan Q et al (2015) DNA methylation age is associated with mortality in a longitudinal Danish twin study. Aging Cell 15:149\u2013154. https:\/\/doi.org\/10.1111\/acel.12421","journal-title":"Aging Cell"},{"key":"947_CR9","doi-asserted-by":"publisher","first-page":"975","DOI":"10.1016\/j.biopsych.2005.12.016","volume":"59","author":"RA Cohen","year":"2006","unstructured":"Cohen RA, Grieve S, Hoth KF et al (2006) Early life stress and morphometry of the adult anterior cingulate cortex and caudate nuclei. Biol Psychiatry 59:975\u2013982. https:\/\/doi.org\/10.1016\/j.biopsych.2005.12.016","journal-title":"Biol Psychiatry"},{"key":"947_CR10","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1212\/WNL.0000000000002209","volume":"86","author":"S Cohen","year":"2016","unstructured":"Cohen S, Caan MWA, Mutsaerts H-J et al (2016) Cerebral injury in perinatally HIV-infected children compared to matched healthy controls. Neurology 86:19\u201327. https:\/\/doi.org\/10.1212\/WNL.0000000000002209","journal-title":"Neurology"},{"key":"947_CR11","doi-asserted-by":"publisher","first-page":"295","DOI":"10.1097\/QAD.0000000000000528","volume":"29","author":"CS Crowell","year":"2015","unstructured":"Crowell CS, Huo Y, Tassiopoulos K et al (2015) Early viral suppression improves neurocognitive outcomes in HIV-infected children. AIDS 29:295\u2013304. https:\/\/doi.org\/10.1097\/QAD.0000000000000528","journal-title":"AIDS"},{"key":"947_CR12","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1186\/1471-2105-9-85","volume":"9","author":"MJ Dunning","year":"2008","unstructured":"Dunning MJ, Barbosa-Morais NL, Lynch AG et al (2008) Statistical issues in the analysis of Illumina data. BMC Bioinformatics 9:85. https:\/\/doi.org\/10.1186\/1471-2105-9-85","journal-title":"BMC Bioinformatics"},{"key":"947_CR13","doi-asserted-by":"publisher","first-page":"207","DOI":"10.1016\/j.conb.2009.05.009","volume":"19","author":"M Fagiolini","year":"2009","unstructured":"Fagiolini M, Jensen CL, Champagne FA (2009) Epigenetic influences on brain development and plasticity. Curr Opin Neurobiol 19:207\u2013212. https:\/\/doi.org\/10.1016\/j.conb.2009.05.009","journal-title":"Curr Opin Neurobiol"},{"key":"947_CR14","doi-asserted-by":"publisher","first-page":"11050","DOI":"10.1073\/pnas.200033797","volume":"97","author":"B Fischl","year":"2000","unstructured":"Fischl B, Dale AM (2000) Measuring the thickness of the human cerebral cortex from magnetic resonance images. Proc Natl Acad Sci 97:11050\u201311055. https:\/\/doi.org\/10.1073\/pnas.200033797","journal-title":"Proc Natl Acad Sci"},{"key":"947_CR15","doi-asserted-by":"publisher","first-page":"118","DOI":"10.1016\/S1053-8119(01)91461-2","volume":"13","author":"B Fischl","year":"2001","unstructured":"Fischl B, Salat D, Kennedy D et al (2001) Automatic segmentation of the structures in the human brain. Neuroimage 13:118. https:\/\/doi.org\/10.1016\/S1053-8119(01)91461-2","journal-title":"Neuroimage"},{"key":"947_CR16","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1016\/j.neuroscience.2012.11.040","volume":"264","author":"K Gapp","year":"2014","unstructured":"Gapp K, Woldemichael BT, Bohacek J, Mansuy IM (2014) Epigenetic regulation in neurodevelopment and neurodegenerative diseases. Neuroscience 264:99\u2013111. https:\/\/doi.org\/10.1016\/j.neuroscience.2012.11.040","journal-title":"Neuroscience"},{"key":"947_CR17","doi-asserted-by":"publisher","first-page":"1132","DOI":"10.1111\/acel.12005","volume":"11","author":"P Garagnani","year":"2012","unstructured":"Garagnani P, Bacalini MG, Pirazzini C et al (2012) Methylation of ELOVL2gene as a new epigenetic marker of age. Aging Cell 11:1132\u20131134. https:\/\/doi.org\/10.1111\/acel.12005","journal-title":"Aging Cell"},{"key":"947_CR18","doi-asserted-by":"publisher","unstructured":"Hoare J, Fouche J-P, Phillips N et al (2018) Structural brain changes in perinatally HIV infected young adolescents in South Africa AIDS 1.https:\/\/doi.org\/10.1097\/QAD.0000000000002024","DOI":"10.1097\/QAD.0000000000002024"},{"key":"947_CR19","doi-asserted-by":"publisher","first-page":"1793","DOI":"10.1097\/QAD.0000000000000766","volume":"29","author":"J Hoare","year":"2015","unstructured":"Hoare J, Fouche J-P, Phillips N et al (2015) White matter micro-structural changes in ART-naive and ART-treated children and adolescents infected with HIV in South Africa. AIDS 29:1793\u20131801. https:\/\/doi.org\/10.1097\/QAD.0000000000000766","journal-title":"AIDS"},{"key":"947_CR20","doi-asserted-by":"publisher","first-page":"205","DOI":"10.1007\/s13365-012-0099-9","volume":"18","author":"J Hoare","year":"2012","unstructured":"Hoare J, Fouche J-P, Spottiswoode B et al (2012) A diffusion tensor imaging and neurocognitive study of HIV-positive children who are HAART-na\u00efve \u201cslow progressors.\u201d J Neurovirol 18:205\u2013212. https:\/\/doi.org\/10.1007\/s13365-012-0099-9","journal-title":"J Neurovirol"},{"key":"947_CR21","doi-asserted-by":"publisher","first-page":"R97","DOI":"10.1186\/gb-2012-13-10-r97","volume":"13","author":"S Horvath","year":"2012","unstructured":"Horvath S, Zhang Y, Langfelder P, Kahn R, Boks M, van Eijk K et al (2012) Aging effects on DNA methylation modules in human brain and blood tissue. Genome Biol 13:R97","journal-title":"Genome Biol"},{"key":"947_CR22","doi-asserted-by":"publisher","first-page":"R115","DOI":"10.1186\/gb-2013-14-10-r115","volume":"14","author":"S Horvath","year":"2013","unstructured":"Horvath S (2013) DNA methylation age of human tissues and cell types. Genome Biol 14:R115. https:\/\/doi.org\/10.1186\/gb-2013-14-10-r115","journal-title":"Genome Biol"},{"key":"947_CR23","doi-asserted-by":"crossref","unstructured":"Horvath S, Levine AJ (2015) HIV-1 infection accelerates age according to the epigenetic clock. J Infect Dis 212:1563-1573","DOI":"10.1093\/infdis\/jiv277"},{"key":"947_CR24","doi-asserted-by":"publisher","first-page":"171","DOI":"10.1186\/s13059-016-1030-0","volume":"17","author":"S Horvath","year":"2016","unstructured":"Horvath S, Gurven M, Levine ME et al (2016) An epigenetic clock analysis of race\/ethnicity, sex, and coronary heart disease. Genome Biol 17:171. https:\/\/doi.org\/10.1186\/s13059-016-1030-0","journal-title":"Genome Biol"},{"key":"947_CR25","doi-asserted-by":"publisher","unstructured":"Horvath S, Phillips N, Heany SJ et al (2018) Perinatally acquired HIV infection accelerates epigenetic aging in South African adolescents AIDS 1.https:\/\/doi.org\/10.1097\/QAD.0000000000001854","DOI":"10.1097\/QAD.0000000000001854"},{"key":"947_CR26","doi-asserted-by":"publisher","first-page":"959","DOI":"10.1097\/QAD.0b013e328352cee7","volume":"26","author":"S Kapetanovic","year":"2012","unstructured":"Kapetanovic S, Aaron L, Montepiedra G et al (2012) T-cell activation and neurodevelopmental outcomes in perinatally HIV-infected children. AIDS 26:959\u2013969. https:\/\/doi.org\/10.1097\/QAD.0b013e328352cee7","journal-title":"AIDS"},{"key":"947_CR27","doi-asserted-by":"publisher","first-page":"355","DOI":"10.1111\/hiv.12220","volume":"16","author":"JR Lazarus","year":"2015","unstructured":"Lazarus JR, Rutstein RM, Lowenthal ED (2015) Treatment initiation factors and cognitive outcome in youth with perinatally acquired HIV infection. HIV Med 16:355\u2013361. https:\/\/doi.org\/10.1111\/hiv.12220","journal-title":"HIV Med"},{"key":"947_CR28","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1001\/archneurol.2007.31","volume":"65","author":"S Letendre","year":"2008","unstructured":"Letendre S, Marquie-Beck J, Capparelli E et al (2008) Validation of the CNS penetration-effectiveness rank for quantifying antiretroviral penetration into the central nervous system. Arch Neurol 65:65\u201370. https:\/\/doi.org\/10.1001\/archneurol.2007.31","journal-title":"Arch Neurol"},{"key":"947_CR29","first-page":"45","volume":"18","author":"SL Letendre","year":"2010","unstructured":"Letendre SL, Ellis RJ, Ances BM, McCutchan JA (2010) Neurologic complications of HIV disease and their treatment. Top HIV Med 18:45\u201355","journal-title":"Top HIV Med"},{"key":"947_CR30","doi-asserted-by":"publisher","first-page":"366","DOI":"10.1007\/s13365-015-0406-3","volume":"22","author":"AJ Levine","year":"2016","unstructured":"Levine AJ, Quach A, Moore DJ et al (2016) Accelerated epigenetic aging in brain is associated with pre-mortem HIV-associated neurocognitive disorders. J Neurovirol 22:366\u2013375. https:\/\/doi.org\/10.1007\/s13365-015-0406-3","journal-title":"J Neurovirol"},{"key":"947_CR31","doi-asserted-by":"publisher","first-page":"2854","DOI":"10.1073\/pnas.1118003109","volume":"109","author":"JL Luby","year":"2012","unstructured":"Luby JL, Barch DM, Belden A et al (2012) Maternal support in early childhood predicts larger hippocampal volumes at school age. Proc Natl Acad Sci USA 109:2854\u20132859. https:\/\/doi.org\/10.1073\/pnas.1118003109","journal-title":"Proc Natl Acad Sci USA"},{"key":"947_CR32","doi-asserted-by":"publisher","first-page":"434","DOI":"10.1038\/nrn2639","volume":"10","author":"SJ Lupien","year":"2009","unstructured":"Lupien SJ, McEwen BS, Gunnar MR, Heim C (2009) Effects of stress throughout the lifespan on the brain, behaviour and cognition. Nat Rev Neurosci 10:434\u2013445. https:\/\/doi.org\/10.1038\/nrn2639","journal-title":"Nat Rev Neurosci"},{"key":"947_CR33","doi-asserted-by":"publisher","first-page":"6","DOI":"10.1186\/s13148-016-0228-z","volume":"8","author":"L Perna","year":"2016","unstructured":"Perna L, Zhang Y, Mons U et al (2016) Epigenetic age acceleration predicts cancer, cardiovascular, and all-cause mortality in a German case cohort. Clin Epigenetics 8:6. https:\/\/doi.org\/10.1186\/s13148-016-0228-z","journal-title":"Clin Epigenetics"},{"key":"947_CR34","doi-asserted-by":"publisher","first-page":"95","DOI":"10.3389\/fnana.2017.00095","volume":"11","author":"SR Randall","year":"2017","unstructured":"Randall SR, Warton CMR, Holmes MJ et al (2017) Larger subcortical gray matter structures and smaller corpora callosa at age 5 years in HIV infected children on early ART. Front Neuroanat 11:95. https:\/\/doi.org\/10.3389\/fnana.2017.00095","journal-title":"Front Neuroanat"},{"key":"947_CR35","doi-asserted-by":"publisher","first-page":"234","DOI":"10.1080\/09297049.2014.898744","volume":"21","author":"R Smith","year":"2014","unstructured":"Smith R, Wilkins M (2014) Perinatally acquired HIV infection: long-term neuropsychological consequences and challenges ahead. Child Neuropsychol 21:234\u2013268. https:\/\/doi.org\/10.1080\/09297049.2014.898744","journal-title":"Child Neuropsychol"},{"key":"947_CR36","doi-asserted-by":"publisher","first-page":"1487","DOI":"10.1016\/j.neuroimage.2006.02.024","volume":"31","author":"SM Smith","year":"2006","unstructured":"Smith SM, Jenkinson M, Johansen-Berg H et al (2006) Tract-based spatial statistics: voxelwise analysis of multi-subject diffusion data. Neuroimage 31:1487\u20131505. https:\/\/doi.org\/10.1016\/j.neuroimage.2006.02.024","journal-title":"Neuroimage"},{"key":"947_CR37","doi-asserted-by":"publisher","first-page":"1429","DOI":"10.1006\/nimg.2002.1267","volume":"17","author":"S-K Song","year":"2002","unstructured":"Song S-K, Sun S-W, Ramsbottom MJ et al (2002) Dysmyelination revealed through MRI as increased radial (but unchanged axial) diffusion of water. Neuroimage 17:1429\u20131436","journal-title":"Neuroimage"},{"key":"947_CR38","doi-asserted-by":"publisher","first-page":"e90","DOI":"10.1093\/nar\/gkt090","volume":"41","author":"TJ Triche Jr","year":"2013","unstructured":"Triche TJ Jr, Weisenberger DJ, Van Den Berg D et al (2013) Low-level processing of Illumina Infinium DNA Methylation BeadArrays. Nucleic Acids Res 41:e90\u2013e90. https:\/\/doi.org\/10.1093\/nar\/gkt090","journal-title":"Nucleic Acids Res"}],"container-title":["Journal of NeuroVirology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s13365-021-00947-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s13365-021-00947-3\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s13365-021-00947-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,6,10]],"date-time":"2022-06-10T16:53:26Z","timestamp":1654880006000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s13365-021-00947-3"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,2,7]]},"references-count":38,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2022,4]]}},"alternative-id":["947"],"URL":"https:\/\/doi.org\/10.1007\/s13365-021-00947-3","relation":{},"ISSN":["1355-0284","1538-2443"],"issn-type":[{"value":"1355-0284","type":"print"},{"value":"1538-2443","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,2,7]]},"assertion":[{"value":"31 March 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"22 December 2020","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"15 January 2021","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"7 February 2021","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Compliance with ethical standards"}},{"value":"The authors declare that they have no conflict of interest.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}]}}