title: Elevated plasma soluble CD14 and skewed CD16+ monocyte distribution persist despite normalisation of soluble CD163 and CXCL10 by effective HIV therapy: a changing paradigm for routine HIV laboratory monitoring?
abstract: OBJECTIVE
  We investigated plasma and flow cytometric biomarkers of monocyte status that have been associated with prognostic utility in HIV infection and other chronic inflammatory diseases, comparing 81 HIV+ individuals with a range of treatment outcomes to a group of 21 healthy control blood donors. Our aim is to develop and optimise monocyte assays that combine biological relevance, clinical utility, and ease of adoption into routine HIV laboratory practice.
  
  
  METHODS
  Cross-sectional evaluation of concurrent plasma and whole blood samples.
  
  
  METHODS
  A flow cytometry protocol was developed comprising single-tube CD45, CD14, CD16, CD64, CD163, CD143 analysis with appropriately matched isotype controls. Plasma levels of soluble CD14 (sCD14), soluble CD163 (sCD163) and CXCL10 were measured by ELISA.
  
  
  RESULTS
  HIV status was associated with significantly increased expression of CD64, CD143 and CD163 on CD16+ monocytes, irrespective of the virological response to HIV therapy. Plasma levels of sCD14, sCD163 and CXCL10 were also significantly elevated in association with viremic HIV infection. Plasma sCD163 and CXCL10 levels were restored to healthy control levels by effective antiretroviral therapy while sCD14 levels remained elevated despite virological suppression (p<0.001).
  
  
  CONCLUSIONS
  Flow cytometric and plasma biomarkers of monocyte activation indicate an ongoing systemic inflammatory response to HIV infection, characterised by persistent alterations of CD16+ monocyte expression profiles and elevated sCD14 levels, that are not corrected by antiretroviral therapy and likely to be prognostically significant. In contrast, sCD163 and CXCL10 levels declined on antiretroviral therapy, suggesting multiple activation pathways revealed by these biomarkers. Incorporation of these assays into routine clinical care is feasible and warrants further consideration, particularly in light of emerging therapeutic strategies that specifically target innate immune activation in HIV infection.
authors.affiliation: Molecular and Biomedical Sciences, School of Veterinary and Life Sciences, Murdoch University, Murdoch, Perth, Western Australia, Australia; Department of Clinical Immunology, Royal Perth Hospital, Wellington Street, Perth, Western Australia, Australia.
authors.forename: Alison
authors.initials: A
authors.lastname: Castley
authors.affiliation: Molecular and Biomedical Sciences, School of Veterinary and Life Sciences, Murdoch University, Murdoch, Perth, Western Australia, Australia.
authors.forename: Cassandra
authors.initials: C
authors.lastname: Berry
authors.affiliation: Department of Clinical Immunology, Royal Perth Hospital, Wellington Street, Perth, Western Australia, Australia; School of Pathology and Laboratory Medicine, University of Western Australia, Nedlands, Perth, Western Australia, Australia.
authors.forename: Martyn
authors.initials: M
authors.lastname: French
authors.affiliation: School of Pathology and Laboratory Medicine, University of Western Australia, Nedlands, Perth, Western Australia, Australia.
authors.forename: Sonia
authors.initials: S
authors.lastname: Fernandez
authors.affiliation: Department of Clinical Immunology, Royal Perth Hospital, Wellington Street, Perth, Western Australia, Australia.
authors.forename: Romano
authors.initials: R
authors.lastname: Krueger
authors.affiliation: Institute for Immunology and Infectious Diseases, Murdoch University, Murdoch, Perth, Western Australia, Australia; Department of Clinical Immunology, Royal Perth Hospital, Wellington Street, Perth, Western Australia, Australia.
authors.forename: David
authors.initials: D
authors.lastname: Nolan
mesh_terms: D000328:Adult; D000368:Aged; D019380:Anti-HIV Agents / Q000494:pharmacology / Q000627:therapeutic use; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism*; D015214:Antigens, Differentiation, Myelomonocytic / Q000235:genetics / Q000378:metabolism*; D016022:Case-Control Studies; D054357:Chemokine CXCL10 / Q000235:genetics / Q000378:metabolism*; D005260:Female; D015658:HIV Infections / Q000097:blood* / Q000188:drug therapy; D006801:Humans; D018950:Lipopolysaccharide Receptors / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D017452:Receptors, IgG / Q000235:genetics / Q000378:metabolism*; D000098902:CD163 Antigen
chemical_list: D019380:Anti-HIV Agents; D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D000098902:CD163 Antigen; D054357:Chemokine CXCL10; D018950:Lipopolysaccharide Receptors; D011956:Receptors, Cell Surface; D017452:Receptors, IgG