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Perinatally acquired HIV infection accelerates epigenetic aging in South African adolescents

Horvath, Stevea,b; Stein, Dan J.c; Phillips, Nicolec; Heany, Sarah J.c; Kobor, Michael S.d; Lin, David T.S.d; Myer, Landone,f; Zar, Heather J.g,h; Levine, Andrew J.i,*; Hoare, Jacquelinec,*

doi: 10.1097/QAD.0000000000001854
CLINICAL SCIENCE
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Objective: Recent studies demonstrate that infection with the HIV-1 is associated with accelerated aging effects in adults according to a highly accurate epigenetic biomarker of aging known as epigenetic clock. However, it is not yet known whether epigenetic age acceleration occurs as early as adolescence in perinatally HIV-infected (PHIV+) youth.

Design: Observational study of PHIV and HIV-uninfected adolescents enrolled in the Cape Town Adolescent Antiretroviral Cohort Study.

Methods: The Illumina EPIC array was used to generate blood DNA methylation data from 204 PHIV and 44 age-matched, uninfected (HIV−) adolescents aged 9–12 years old. The epigenetic clock software and method was used to estimate two measures of epigenetic age acceleration. Each participant completed a comprehensive neuropsychological test battery upon enrollment to Cape Town Adolescent Antiretroviral Cohort.

Results: HIV is associated with biologically older blood in PHIV+ adolescents according to both measures of epigenetic age acceleration. One of the measures, extrinsic epigenetic age acceleration, is negatively correlated with measures of cognitive functioning (executive functioning, working memory, processing speed).

Conclusion: Overall, our results indicate that epigenetic age acceleration in blood can be observed in PHIV+ adolescents and that these epigenetic changes accompany poorer cognitive functioning.

aDepartment of Human Genetics, David Geffen School of Medicine

bDepartment of Biostatistics, School of Public Health, University of California, Los Angeles, Los Angeles, California, USA

cMRC Unit on Risk & Resilience in Mental Disorders, Department of Psychiatry and Mental Health, University of Cape Town, J-Block, Groote Schuur Hospital, Observatory, Cape Town, South Africa

dCentre for Molecular Medicine and Therapeutics, Department of Medical Genetics, British Columbia Children's Hospital Research Institute, Vancouver, British Columbia, Canada

eCentre for Infectious Disease Epidemiology and Research

fDivision of Epidemiology and Biostatistics, School of Public Health & Family Medicine, University of Cape Town

gDepartment of Paediatrics and Child Health, Red Cross War Memorial Children's Hospital

hSA-Medical Research Council Unit on Child and Adolescent Health, University of Cape Town, South Africa

iDepartment of Neurology, David Geffen School of Medicine at the University of California, Los Angeles, Los Angeles, California, USA.

Correspondence to Andrew J. Levine, Department of Neurology, David Geffen School of Medicine at the University of California, Los Angeles, Los Angeles, California, USA. E-mail: AJLevine@mednet.ucla.edu

Received 19 January, 2018

Revised 13 April, 2018

Accepted 16 April, 2018

Copyright © 2018 Wolters Kluwer Health, Inc.