title: Absolute leukocyte telomere length in HIV-infected and uninfected individuals: evidence of accelerated cell senescence in HIV-associated chronic obstructive pulmonary disease.
abstract: Combination antiretroviral therapy (cART) has extended the longevity of human immunodeficiency virus (HIV)-infected individuals. However, this has resulted in greater awareness of age-associated diseases such as chronic obstructive pulmonary disease (COPD). Accelerated cellular senescence may be responsible, but its magnitude as measured by leukocyte telomere length is unknown and its relationship to HIV-associated COPD has not yet been established. We measured absolute telomere length (aTL) in peripheral leukocytes from 231 HIV-infected adults. Comparisons were made to 691 HIV-uninfected individuals from a population-based sample. Subject quartiles of aTL were assessed for relationships with measures of HIV disease severity, airflow obstruction, and emphysema severity on computed tomographic (CT) imaging. Multivariable regression models identified factors associated with shortened aTL. Compared to HIV-uninfected subjects, the mean aTL in HIV-infected patients was markedly shorter by 27 kbp/genome (p<0.001); however, the slopes of aTL vs. age were not different (p=0.469). Patients with longer known durations of HIV infection (p=0.019) and lower nadir CD4 cell counts (p=0.023) had shorter aTL. Shorter aTL were also associated with older age (p=0.026), smoking (p=0.005), reduced forced expiratory volume in one second (p=0.030), and worse CT emphysema severity score (p=0.049). HIV-infected subjects demonstrate advanced cellular aging, yet in a cART-treated cohort, the relationship between aTL and age appears no different from that of HIV-uninfected subjects.
authors.affiliation: Centre for Heart Lung Innovation, Vancouver, BC, Canada.
authors.forename: Joseph C Y
authors.initials: JC
authors.lastname: Liu
authors.affiliation: Centre for Heart Lung Innovation, Vancouver, BC, Canada.
authors.forename: Janice M
authors.initials: JM
authors.lastname: Leung
authors.affiliation: Centre for Heart Lung Innovation, Vancouver, BC, Canada.
authors.forename: David A
authors.initials: DA
authors.lastname: Ngan
authors.affiliation: AIDS Research Program, St. Paul's Hospital, Vancouver, BC, Canada.
authors.forename: Negar F
authors.initials: NF
authors.lastname: Nashta
authors.affiliation: Department of Family Medicine, Faculty of Medicine, University of British Columbia, Vancouver, Canada; Division of HIV/AIDS, Department of Medicine, University of British Columbia, Vancouver, Canada; BC Centre for Excellence in HIV/AIDS, St. Paul's Hospital, Vancouver, BC, Canada.
authors.forename: Silvia
authors.initials: S
authors.lastname: Guillemi
authors.affiliation: AIDS Research Program, St. Paul's Hospital, Vancouver, BC, Canada; Department of Family Medicine, Faculty of Medicine, University of British Columbia, Vancouver, Canada; Division of HIV/AIDS, Department of Medicine, University of British Columbia, Vancouver, Canada.
authors.forename: Marianne
authors.initials: M
authors.lastname: Harris
authors.affiliation: BC Centre for Excellence in HIV/AIDS, St. Paul's Hospital, Vancouver, BC, Canada.
authors.forename: Viviane D
authors.initials: VD
authors.lastname: Lima
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Department of Medicine, Dong-A University, Busan, South Korea.
authors.forename: Soo-Jung
authors.initials: SJ
authors.lastname: Um
authors.affiliation: Centre for Heart Lung Innovation, Vancouver, BC, Canada.
authors.forename: Yuexin
authors.initials: Y
authors.lastname: Li
authors.affiliation: Centre for Heart Lung Innovation, Vancouver, BC, Canada.
authors.forename: Sheena
authors.initials: S
authors.lastname: Tam
authors.affiliation: UBC Department of Medicine and Division of Respiratory Medicine, St. Paul's Hospital, Vancouver, BC, Canada.
authors.forename: Tawimas
authors.initials: T
authors.lastname: Shaipanich
authors.affiliation: Department of Radiology and Diagnostic Imaging, St. Paul's Hospital, Vancouver, BC, Canada.
authors.forename: Rekha
authors.initials: R
authors.lastname: Raju
authors.affiliation: Department of Radiology and Diagnostic Imaging, St. Paul's Hospital, Vancouver, BC, Canada.
authors.forename: Cameron
authors.initials: C
authors.lastname: Hague
authors.affiliation: Department of Radiology and Diagnostic Imaging, St. Paul's Hospital, Vancouver, BC, Canada.
authors.forename: Jonathon A
authors.initials: JA
authors.lastname: Leipsic
authors.affiliation: Respiratory Epidemiology and Clinical Research Unit, Montreal Chest Institute, McGill University, Montreal, Quebec, Canada.
authors.forename: Jean
authors.initials: J
authors.lastname: Bourbeau
authors.affiliation: Centre for Heart Lung Innovation, Vancouver, BC, Canada.
authors.forename: Wan C
authors.initials: WC
authors.lastname: Tan
authors.affiliation: BC Centre for Excellence in HIV/AIDS, St. Paul's Hospital, Vancouver, BC, Canada.
authors.forename: P Richard
authors.initials: PR
authors.lastname: Harrigan
authors.affiliation: Centre for Heart Lung Innovation, Vancouver, BC, Canada; UBC Department of Medicine and Division of Respiratory Medicine, St. Paul's Hospital, Vancouver, BC, Canada.
authors.forename: Don D
authors.initials: DD
authors.lastname: Sin
authors.affiliation: Division of HIV/AIDS, Department of Medicine, University of British Columbia, Vancouver, Canada; BC Centre for Excellence in HIV/AIDS, St. Paul's Hospital, Vancouver, BC, Canada.
authors.forename: Julio
authors.initials: J
authors.lastname: Montaner
authors.affiliation: Centre for Heart Lung Innovation, Vancouver, BC, Canada; UBC Department of Medicine and Division of Respiratory Medicine, St. Paul's Hospital, Vancouver, BC, Canada.
authors.forename: S F Paul
authors.initials: SF
authors.lastname: Man
mesh_terms: D000328:Adult; D016922:Cellular Senescence / Q000235:genetics*; D015331:Cohort Studies; D005260:Female; D015658:HIV Infections / Q000097:blood / Q000150:complications / Q000235:genetics*; D006801:Humans; D007962:Leukocytes / Q000648:ultrastructure*; D008297:Male; D008875:Middle Aged; D029424:Pulmonary Disease, Chronic Obstructive / Q000150:complications* / Q000473:pathology; D016615:Telomere