A Review of Premature Frailty in HIV-Infected Persons; Another Manifestation of HIV-Related Accelerated Aging

Nur      F. Onen; E.      Turner Overton

doi:10.2174/1874609811104010033

Abstract

Purpose: HIV-related immunological and multisystem accelerated aging contributes to the premature occurrence of agerelated comorbidities. Such non-AIDS-defining comorbidities include cardiovascular disease, dyslipidemia, osteoporosis and frailty, and are of increasing importance with improved survival on antiretrovirals. This review will describe the underlying pathogenesis of HIVrelated accelerated aging and will thereafter focus on frailty, a clinical concept which has only recently been studied in the HIV field. Methods: A literature search was performed using PubMed. Cited articles were peer reviewed and included prospective, retrospective and basic science studies, systematic reviews and Centers for Disease Control and Prevention data. Results: HIV infection is characterized by profound immune dysregulation, which can hasten cardiovascular, renal, cerebrovascular and bone disease and precede their overt manifestation by years. Viral mediated atherogenesis further accelerates end organ dysfunction and increases mortality. Frailty, a clinical syndrome characterized by multisystem dysregulation and increased vulnerability to stressors, occurs prematurely in HIV-infected persons especially those with advanced disease. Frailty prevalence and clinical characteristics are similar in affected older adults and HIV-infected persons. Its presence is associated with a number of negative outcomes including greater comorbidity and hospitalzation. Conclusion: Premature frailty, like other non-AIDS-defining comorbidities, is a manifestation of HIV-related accelerated aging. The synergism of HIV infection and aging has alarming clinical and socioeconomic implications. Research is needed to identify the factors that predict the development of premature frailty among HIV-infected persons and the optimal prevention and management strategies.

Keywords: Frailty, HIV infection, accelerated aging, comorbidities, dyslipidemia, osteoporosis, antiretrovirals, atherogenesis, low bone mineral density, neurocognitive impairment, diabetes mellitus, malignancy, combination antiretroviral therapy (cART), pathogenesis, adaptive immune systems, CD4+ T cell, lymphocyte apoptosis, lymphocytes, natural killer cells, macrophages, cytokines, chemokines, lipopolysaccharide, CD8+ T cells, cytomegalovirus, homeostatis mechanisms, apoptosis, interleukin-6, tumor necrosis factor, highly sensitive C-reactive protein (hsCRP), central nervous system (CNS), leucocyte, amyloid, Alzheimer's Diseases, endothelial, endotheliopathic effect, nitric oxide synthase system, proatherogenic lipid, seronegative, homeostasis, neuropsychiatric comorbidity, HIV-seronegative, testosterone, depression, glucocorticoid, hypothalamic-pituitary-adrenal (HPA) axis, chemokine, albumin, liposaccharidemia, neuroendocrine