Journal Article

Absolute Leukocyte Telomere Length in HIV-Infected and Uninfected Individuals: Evidence of Accelerated Cell Senescence in HIV-Associated Chronic Obstructive Pulmonary Disease

Lima, Viviane D., Guillemi, Silvia, Harris, Marianne, Um, Soo-Jung, Leung, Janice M., Liu, Joseph C. Y., Sin, Don D., Nashta, Negar F., Tam, Sheena, Bourbeau, Jean, Raju, Rekha, Hague, Cameron, Leipsic, Jonathon A., Man, S. F. Paul, Ngan, David A., Harrigan, P. Richard, Montaner, Julio, Tan, Wan C., Shaipanich, Tawimas, Li, Yuexin

2015

Overview

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.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Adult / Adults / Age / Aging / Air flow / Antiretroviral agents / Antiretroviral therapy / CD4 antigen / Cellular Senescence - genetics / Chronic obstructive lung disease / Chronic obstructive pulmonary disease / Cohort Studies / Computed tomography / Emphysema / Female / Genomes / Health aspects / Highly active antiretroviral therapy / HIV / HIV infections / HIV Infections - blood / HIV Infections - complications / HIV Infections - genetics / HIV patients / Human immunodeficiency virus / Humans / Leukocytes / Leukocytes - ultrastructure / Lung diseases / Male / Medical diagnosis / Middle Aged / Obstructive lung disease / Patients / Pulmonary Disease, Chronic Obstructive - complications / Pulmonary Disease, Chronic Obstructive - pathology / Quartiles / Regression analysis / Regression models / Senescence / Smoking / Telomere / Viruses