title: Increased inflammation but similar physical composition and function in older-aged, HIV-1 infected subjects.
abstract: BACKGROUND
  Systemic immune activation (inflammation) and immunosenescence develop in some people with advancing age. This process, known as "inflamm-aging," is associated with physical frailty and sarcopenia. Meanwhile, successful antiretroviral therapy has led to a growing number of older HIV-1-infected individuals who face both age-related and HIV-1-related inflammation, which may synergistically promote physical decline, including frailty and sarcopenia. The purpose of our study was to determine if inflammation during treated HIV-1 infection worsens physical impairment in older individuals.
  
  
  METHODS
  We determined the severity of HIV-associated inflammation and physical performance (strength and endurance) in 21 older HIV-infected individuals (54-69 years) receiving suppressive antiretroviral therapy, balanced for confounding variables including age, anthropometrics, and co-morbidities with 10 uninfected control individuals. Biomarkers for microbial translocation (lipopolysaccharide [LPS]), inflammation (soluble CD14 [sCD14], osteopontin, C-reactive protein [CRP], interleukin-6 [IL-6], soluble ICAM-1 [sICAM-1] and soluble VCAM-1 [sVCAM-1]), and coagulopathy (D-dimer) were assayed in plasma. Activation phenotypes of CD4(+)T cells, CD8(+) T cells and monocytes were measured by flow cytometry. Physical performance was measured by 400 m walking speed, a short physical performance battery [SPPB], and lower extremity muscle strength and fatigue.
  
  
  RESULTS
  Overall physical function was similar in the uninfected and HIV-infected groups. Compared to uninfected individuals, the HIV-infected group had elevated levels of sCD14 (P < 0.001), CRP (P < 0.001) and IL-6 (P = 0.003) and an increased frequency of CD4(+) and CD8(+) T cells with an immunosenescent CD57(+) phenotype (P = 0.004 and P = 0.043, respectively). Neither plasma inflammatory biomarkers nor CD57(+) T cells correlated with CD4(+) T cell counts. Furthermore, none of the elevated inflammatory biomarkers in the HIV-infected subjects were associated with any of the physical performance results.
  
  
  CONCLUSIONS
  When age-related co-morbidities were carefully balanced between the uninfected and HIV-infected groups, no evidence of inflammation-associated physical impairment was detected. Despite careful balancing for age, BMI, medications and co-morbidities, the HIV-infected group still displayed evidence of significant chronic inflammation, including elevated sCD14, CRP, IL-6 and CD57(+) T cells, although the magnitude of this inflammation was unrelated to physical impairment.
authors.affiliation: Department of Pathology, Immunology and Laboratory Medicine, University of Florida, Box 100275, Gainesville, FL, 32610-0275, USA. mawallet@pathology.ufl.edu.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Wallet
authors.affiliation: Department of Aging and Geriatric Research, University of Florida, Gainesville, FL, USA. tbuford@ufl.edu.
authors.forename: Thomas W
authors.initials: TW
authors.lastname: Buford
authors.affiliation: Department of Aging and Geriatric Research, University of Florida, Gainesville, FL, USA. amjoseph@ufl.edu.
authors.forename: Anna-Maria
authors.initials: AM
authors.lastname: Joseph
authors.affiliation: Department of Medicine, Division of Infectious Diseases, University of Florida, Gainesville, FL, USA. msankuratri@gmail.com.|Department of Medicine, Division of Infectious Diseases, Malcom Randall VA Medical Center, Gainesville, FL, USA. msankuratri@gmail.com.
authors.forename: Madhuri
authors.initials: M
authors.lastname: Sankuratri
authors.affiliation: Department of Aging and Geriatric Research, University of Florida, Gainesville, FL, USA. cleeuwen@ufl.edu.
authors.forename: Christiaan
authors.initials: C
authors.lastname: Leeuwenburgh
authors.affiliation: Department of Aging and Geriatric Research, University of Florida, Gainesville, FL, USA. mpahor@ufl.edu.
authors.forename: Marco
authors.initials: M
authors.lastname: Pahor
authors.affiliation: Department of Aging and Geriatric Research, University of Florida, Gainesville, FL, USA. tmanini@ufl.edu.
authors.forename: Todd
authors.initials: T
authors.lastname: Manini
authors.affiliation: Department of Pediatrics, Division of Allergy and Immunology, Duke University, Durham, NC, USA. john.sleasman@duke.edu.
authors.forename: John W
authors.initials: JW
authors.lastname: Sleasman
authors.affiliation: Department of Pathology, Immunology and Laboratory Medicine, University of Florida, Box 100275, Gainesville, FL, 32610-0275, USA. goodenow@ufl.edu.
authors.forename: Maureen M
authors.initials: MM
authors.lastname: Goodenow
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood; D002452:Cell Count; D015331:Cohort Studies; D015658:HIV Infections / Q000276:immunology* / Q000382:microbiology; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007113:Immunity, Innate; D007156:Immunologic Memory; D007249:Inflammation / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism; D009043:Motor Activity; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D015415:Biomarkers