title: Identification of HIV infection-related DNA methylation sites and advanced epigenetic aging in HIV-positive, treatment-naive U.S. veterans.
abstract: HIV-positive individuals are at higher risk than healthy persons for aging-related diseases, including myocardial infarction and non-AIDS defining cancers. Recent evidence suggests that HIV infection may modulate changes in the host cell epigenome, and these changes represent a potential mechanism through which HIV infection accelerates aging. We assessed the difference in DNA methylation (DNAm) age, an aging marker involving multiple age-related cytosine-guanine dinucleotide (CpG) sites, among antiretroviral treatment (ART)-naive HIV-positive and HIV-negative individuals in a cohort of veterans from the Veterans Aging Cohort Study.
  
  
  
  Peripheral blood samples were collected from 19 ART-naive, HIV-positive, and 19 HIV-negative male participants, matched by age and race. Blood samples were collected from HIV-positive participants 7-11 years after ART initiation.
  
  
  
  We compared DNAm age between HIV-positive and HIV-negative groups at baseline and between HIV-positive patients at baseline and follow-up. We also performed an epigenome-wide analysis to identify CpG methylation sites associated with HIV infection.
  
  
  
  DNAm age in HIV-positive individuals is, on average, 11.2 years higher than HIV study participants at baseline, and two of 10 HIV-positive individuals showed an increase in DNAm age after ART initiation. Epigenome-wide association studies showed an association of HIV infection with one site, in gene VPS37B, which approached statistical significance in our cohort (P = 3.30 × 10, Bonferroni-corrected threshold = 1.22 × 10) and was replicated in a second, larger cohort.
  
  
  
  ART treatment-naive HIV-positive individuals have significantly older DNAm age compared to HIV-negative individuals in the Veterans Aging Cohort Study cohort. Longitudinal changes in DNAm age are highly variable across individuals after initiation of antiretroviral therapy.
authors.affiliation: aDepartment of Epidemiology, Emory University Rollins School of Public Health bDivision of Infectious Diseases, Emory University School of Medicine cAtlanta Veterans Affairs Medical Center, Atlanta, Georgia dDepartment of Psychiatry, Yale School of Medicine, New Haven eConnecticut Veteran Health System, West Haven, Connecticut fCardiovascular Medicine Division, Vanderbilt University School of Medicine and Tennessee Valley Healthcare System, Nashville, Tennessee gYale University School of Medicine, New Haven, Connecticut hDepartment of Global Health, Emory University Rollins School of Public Health iDepartment of Biomedical Informatics, Emory University School of Medicine, Atlanta, Georgia, USA.
authors.forename: Kristin N
authors.initials: KN
authors.lastname: Nelson
authors.forename: Qin
authors.initials: Q
authors.lastname: Hui
authors.forename: David
authors.initials: D
authors.lastname: Rimland
authors.forename: Ke
authors.initials: K
authors.lastname: Xu
authors.forename: Matthew S
authors.initials: MS
authors.lastname: Freiberg
authors.forename: Amy C
authors.initials: AC
authors.lastname: Justice
authors.forename: Vincent C
authors.initials: VC
authors.lastname: Marconi
authors.forename: Yan V
authors.initials: YV
authors.lastname: Sun
mesh_terms: D000375:Aging / Q000473:pathology*; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D005500:Follow-Up Studies; D055106:Genome-Wide Association Study; D015658:HIV Infections / Q000473:pathology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D014481:United States; D014728:Veterans