title: Viremic and Virologically Suppressed HIV Infection Increases Age-Related Changes to Monocyte Activation Equivalent to 12 and 4 Years of Aging, Respectively.
abstract: BACKGROUND
  Chronic inflammation and immune activation occur in both HIV infection and normal aging and are associated with inflammatory disease. However, the degree to which HIV influences age-related innate immune changes, and the biomarkers which best reflect them, remains unclear.
  
  
  RESULTS
  We measured established innate immune aging biomarkers in 309 individuals including 88 virologically suppressed (VS) and 52 viremic (viral load ≤ and >50 copies per milliliter, respectively) HIV-positive individuals. Levels of soluble (ie, CXCL10, soluble CD163, neopterin) and cellular (ie, proportions of inflammatory CD16 monocytes) biomarkers of monocyte activation were increased in HIV-positive individuals and were only partially ameliorated by viral suppression. Viremic and VS HIV-positive individuals show levels of age-related monocyte activation biomarkers that are similar to uninfected controls aged 12 and 4 years older, respectively. Viremic HIV infection was associated with an accelerated rate of change of some monocyte activation markers (eg, neopterin) with age, whereas in VS individuals, subsequent age-related changes occurred at a similar rate as in controls, albeit at a higher absolute level. We further identified CXCL10 as a robust soluble biomarker of monocyte activation, highlighting the potential utility of this chemokine as a prognostic marker.
  
  
  CONCLUSIONS
  These findings may partially explain the increased prevalence of inflammatory age-related diseases in HIV-positive individuals and potentially indicate the pathological mechanisms underlying these diseases, which persist despite viral suppression.
authors: *Centre for Biomedical Research, Burnet Institute, Melbourne, Australia; †School of Applied Sciences, RMIT University, Melbourne, Australia; ‡Department of Infectious Diseases, Monash University, Melbourne, Australia; §School of Medical Sciences, University of New South Wales, Sydney, Australia; ‖Department of Microbiology and Immunology, Rush University Medical Center, Chicago, IL; ¶Infectious Diseases Unit, Alfred Hospital, Melbourne, Australia; and #Department of Immunology, Monash University, Melbourne, Australia.
authors: Thomas A
authors: TA
authors: Angelovich
authors: Anna C
authors: AC
authors: Hearps
authors: Anna
authors: A
authors: Maisa
authors: Genevieve E
authors: GE
authors: Martin
authors: Gregor F
authors: GF
authors: Lichtfuss
authors: Wan-Jung
authors: WJ
authors: Cheng
authors: Clovis S
authors: CS
authors: Palmer
authors: Alan L
authors: AL
authors: Landay
authors: Suzanne M
authors: SM
authors: Crowe
authors: Anthony
authors: A
authors: Jaworowski
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging; D015703:Antigens, CD / Q000032:analysis; D015214:Antigens, Differentiation, Myelomonocytic / Q000032:analysis; D015415:Biomarkers / Q000032:analysis; D054357:Chemokine CXCL10 / Q000032:analysis; D015331:Cohort Studies; D005260:Female; D058851:GPI-Linked Proteins / Q000032:analysis; D015658:HIV Infections / Q000276:immunology*; D006801:Humans; D007155:Immunologic Factors / Q000032:analysis; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000737:chemistry / Q000276:immunology*; D019798:Neopterin / Q000032:analysis; D011956:Receptors, Cell Surface / Q000032:analysis; D017452:Receptors, IgG / Q000032:analysis; D055815:Young Adult; D000098902:CD163 Antigen
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D015415:Biomarkers; D000098902:CD163 Antigen; C114753:CXCL10 protein, human; D054357:Chemokine CXCL10; C428200:FCGR3B protein, human; D058851:GPI-Linked Proteins; D007155:Immunologic Factors; D011956:Receptors, Cell Surface; D017452:Receptors, IgG; D019798:Neopterin