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.
Highlights
Combination antiretroviral therapy has lengthened the life expectancy of patients living with human immunodeficiency virus (HIV) [1]
We have quantified absolute telomere length (aTL) shortening in an HIV-infected population, identifying a mean telomere length difference of approximately 27 kbp/genome when compared to a general population sample
Our population of Combination antiretroviral therapy (cART)-treated HIV-infected patients demonstrated a slope of aTL vs. age that was similar to that of an HIVuninfected cohort
Summary
Combination antiretroviral therapy (cART) has lengthened the life expectancy of patients living with human immunodeficiency virus (HIV) [1]. Fewer HIV-infected individuals die from opportunistic infections and AIDS-related cancers [2]; instead, they face chronic conditions normally associated with old age. Studies have identified an increased prevalence of chronic obstructive pulmonary disease (COPD) within HIV-infected populations even after adjustment for age and smoking [3,4,5]. Clinical manifestations of COPD in the HIV population appear to be far more severe [6] and develop earlier than in HIV-uninfected individuals [4]. Disease models of accelerated cellular senescence apply well to HIV [7] and may explain the propensity towards age-associated conditions. In HIV, leukocyte telomere lengths, a marker of cellular aging, are comparatively shorter when measured against uninfected patients [8,9,10]. Immune activation and microbial translocation are thought to drive telomere shortening in HIV [12], but the magnitude of telomere shortening that occurs upon infection with HIV remains unknown
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