Abstract
Telomere length (TL) is a marker of cellular and biological aging. Human immunodeficiency virus (HIV) infection has been reported to be associated with short TLs, which suggests that accelerated biological aging occurs in some cellular compartments of HIV+ individuals. In this study, we measured the TLs of peripheral leukocytes of HIV+ and healthy individuals and examined the biological and environmental correlates of TL. We also investigated the influence of TL on leukoaraiosis, an indicator of cerebral small vessel disease, in HIV+ individuals. Three hundred and twenty-five HIV+ individuals who received stable combination antiretroviral therapy (cART) for >1 year and achieved viral loads of <40 RNA copies/mL were enrolled along with 147 healthy individuals. Relative TLs of leukocytes were estimated by quantitative real-time polymerase chain reaction. Leukoaraiosis was assessed in 184 HIV+ individuals by fluid-attenuated inversion recovery magnetic resonance imaging. We analyzed several covariates, including markers of HIV infection, cART, and social/environmental factors; variables associated with TL length in univariate analyses were incorporated into multivariate models. The TLs of peripheral leukocytes of HIV+ individuals were significantly shorter than those of healthy individuals, and the rate of LT length decline with increasing age was greater. Linear regression analysis showed that in HIV+ individuals, increasing age, cART without integrase-stand transfer inhibitors (INSTI), failure to achieve viral loads of <40 copies/mL within 1 year of initiating cART, and substance use were significantly associated with shorter TLs, even after adjustment for the effects of age. Logistic regression analysis indicated an increasing risk of leukoaraiosis was associated with older age, shorter TLs, hypertension, and carotid artery plaque. Multivariate regression analysis indicated that older age and shorter TLs were significant risk factors for leukoaraiosis. In summary, our data showed that TL shortening in HIV+ individuals was independently associated with leukoaraiosis, and was associated with age, control of viral loads, use of INSTI, and substance use. Our results suggest that effective viral control and less toxic cART can help reduce TL shortening and improve outcomes among HIV+ individuals.
Highlights
Human immunodeficiency virus (HIV)+ individuals are at increased risk of age-related non- acquired immunodeficiency syndrome (AIDS) morbidity and mortality compared with healthy individuals
In linear regression analyses to identify factors associated with leukocyte TL (LTL) in HIV+ individuals, variables associated with telomere length (TL) length in univariate analyses were incorporated into multivariate models
The proportion of more mature and differentiated innate and adaptive immune cells with shorter TLs increase among peripheral blood leukocytes (PBLs), which accounts for the reduced LTLs observed in HIV+ individuals
Summary
HIV+ individuals are at increased risk of age-related non- acquired immunodeficiency syndrome (AIDS) morbidity and mortality compared with healthy individuals. Measures of telomere length (TL) have shown synchronicity across tissues in the same individual [4,5] For this reason, TL is an indicator of cellular senescence [6] and is considered an effective and validated biomarker of aging. HIV infection has been reported to be associated with short TLs. During HIV infection several factors, such as chronic immune activation, inflammation, oxidative stress, HIV proteins, and cART, may contribute to premature TL shortening [10,14,15]. Leukoaraiosis has been reported to be associated with both HIV infection [16] and advancing age [17], and represents several different changes in white matter such as partial loss of myelin, oligodendroglia and axons, fibrohyalinosis, activation of macrophages, and dilated perivascular spaces [18,19]. We investigated the relationship between leukoaraiosis and LTL and examined the usefulness of LTL as a biomarker of brain aging
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