title: Association of functional impairment with inflammation and immune activation in HIV type 1-infected adults receiving effective antiretroviral therapy.
abstract: BACKGROUND
  The relationships of inflammation, immune activation, and immunosenescence markers with functional impairment in aging human immunodeficiency virus type 1 (HIV-1)-infected persons are unknown.
  
  
  METHODS
  HIV-infected persons who were aged 45-65 years, had a plasma HIV-1 RNA load of <48 copies/mL, and were receiving antiretroviral therapy underwent standardized functional testing. In a nested case-control analysis, low-functioning cases were matched (1:1-2) by age, sex, and HIV-1 diagnosis date to high-functioning controls. Markers of inflammation, T-cell activation, microbial translocation, immunosenescence, and immune recovery were used to estimate functional status in conditional logistic regression. Primary analyses were adjusted for CD4(+) T-cell count, smoking, and hepatitis.
  
  
  RESULTS
  Thirty-one low-functioning cases were compared to 49 high-functioning controls. After statistical adjustment, lower proportions of CD4(+) T cells and higher proportion of CD8(+) T cells, higher CD38/HLA-DR expression on CD8(+) T cells, and higher interleukin-6 were associated with a significantly greater odds of low functional status (odds ratio, ≥ 1.1 for all analyses; P ≤ .03). Other inflammatory, senescence, and microbial translocation markers were not significantly different (P ≥ .11 for all analyses) between low-functioning and high-functioning groups.
  
  
  CONCLUSIONS
  Functional impairment during successful antiretroviral therapy was associated with higher CD8(+) T-cell activation and interleukin 6 levels. Interventions to decrease immune activation and inflammation should be evaluated for their effects on physical function and frailty.
authors.affiliation: Division of Infectious Diseases, University of Colorado, Denver, USA. kristine.erlandson@ucdenver.edu
authors.forename: Kristine M
authors.initials: KM
authors.lastname: Erlandson
authors.forename: Amanda A
authors.initials: AA
authors.lastname: Allshouse
authors.forename: Catherine M
authors.initials: CM
authors.lastname: Jankowski
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Lee
authors.forename: Kevin M
authors.initials: KM
authors.lastname: Rufner
authors.forename: Brent E
authors.initials: BE
authors.lastname: Palmer
authors.forename: Cara C
authors.initials: CC
authors.lastname: Wilson
authors.forename: Samantha
authors.initials: S
authors.lastname: MaWhinney
authors.forename: Wendy M
authors.initials: WM
authors.lastname: Kohrt
authors.forename: Thomas B
authors.initials: TB
authors.lastname: Campbell
mesh_terms: D051997:ADP-ribosyl Cyclase 1 / Q000276:immunology; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods; D018791:CD4 Lymphocyte Count / Q000379:methods; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000821:virology; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000821:virology; D016022:Case-Control Studies; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007249:Inflammation / Q000276:immunology / Q000821:virology; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D008562:Membrane Glycoproteins / Q000276:immunology; D008875:Middle Aged; D019562:Viral Load / Q000187:drug effects / Q000276:immunology
chemical_list: D008562:Membrane Glycoproteins; C498154:CD38 protein, human; D051997:ADP-ribosyl Cyclase 1
keywords: HIV; aging; frailty; functional capacity; functional impairment; functional status; immune activation; immunosenescence; inflammation; microbial translocation; physical function; senescence; telomeres
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