title: Frailty and Circulating Markers of Inflammation in HIV+ and HIV- Men in the Multicenter AIDS Cohort Study.
abstract: BACKGROUND
  Frailty is associated with immune activation and inflammation in the elderly general population, but whether this is true in the younger HIV-infected (HIV+) population is not known.
  
  
  METHODS
  We analyzed 24 serologic biomarkers of monocyte, T-cell, or B-cell activation in HIV- (n = 207) and HIV+ (n = 714; 75% virologically suppressed) men who have sex with men in the Multicenter AIDS Cohort Study (MACS) and were classified as frail or nonfrail according to expression or nonexpression of the frailty phenotype at 2 consecutive study visits.
  
  
  RESULTS
  After correction for multiple comparisons and adjustment for age, race, study site, and education, frailty in HIV+ men was significantly (P < 0.002) associated with higher levels of sCD14, sIL2Rα, sTNF-R2, IL-6, and TNF-α; the association with higher levels of C-reactive protein (CRP) approached significance (P = 0.003). After further adjustment for body mass index (BMI), smoking, and comorbidities, only the association with C-reactive protein was significant at P < 0.002, with levels approximately 50% higher in frail compared with nonfrail men. These conclusions were not altered by restricting the analysis to HIV+ men who were virologically suppressed. Among HIV- men, none of these markers differed significantly by frailty.
  
  
  CONCLUSIONS
  These data suggest that frailty in virologically suppressed HIV+ men was associated with immune activation beyond that due to treated HIV infection. The inflammatory markers associated with frailty were primarily products of activated monocytes/macrophages. Much, but not all, activation was accounted for by harmful behaviors and comorbidities. However, C-reactive protein, which is regulated by IL-6, was elevated in HIV+ frail men independent of these factors.
authors.affiliation: *Johns Hopkins Bloomberg School of Public Health, Baltimore, MD;†David Geffen School of Medicine at UCLA and UCLA Fielding School of Public Health, Los Angeles, CA;‡Northwestern University Feinberg School of Medicine, Chicago, IL; and§University of Ohio School of Medicine, Columbus, OH.
authors.forename: Joseph B
authors.initials: JB
authors.lastname: Margolick
authors.forename: Jay H
authors.initials: JH
authors.lastname: Bream
authors.forename: Otoniel
authors.initials: O
authors.lastname: Martínez-Maza
authors.forename: Joe
authors.initials: J
authors.lastname: Lopez
authors.forename: Xiuhong
authors.initials: X
authors.lastname: Li
authors.forename: John P
authors.initials: JP
authors.lastname: Phair
authors.forename: Susan L
authors.initials: SL
authors.lastname: Koletar
authors.forename: Lisa P
authors.initials: LP
authors.lastname: Jacobson
mesh_terms: D000375:Aging / Q000276:immunology*; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods; D015415:Biomarkers / Q000378:metabolism; D015992:Body Mass Index; D002097:C-Reactive Protein / Q000378:metabolism; D018023:HIV Seronegativity / Q000276:immunology*; D006679:HIV Seropositivity / Q000276:immunology*; D015497:HIV-1 / Q000187:drug effects / Q000276:immunology*; D006801:Humans; D007249:Inflammation / Q000188:drug therapy / Q000276:immunology*; D008137:Longitudinal Studies; D008213:Lymphocyte Activation / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D014481:United States
chemical_list: D015415:Biomarkers; D002097:C-Reactive Protein