title: Reduced sTWEAK and increased sCD163 levels in HIV-infected patients: modulation by antiretroviral treatment, HIV replication and HCV co-infection.
abstract: BACKGROUND
  Patients infected with the human immunodeficiency virus (HIV) have an increased risk of cardiovascular disease due to increased inflammation and persistent immune activation. CD163 is a macrophage scavenger receptor that is involved in monocyte-macrophage activation in HIV-infected patients. CD163 interacts with TWEAK, a member of the TNF superfamily. Circulating levels of sTWEAK and sCD163 have been previously associated with cardiovascular disease, but no previous studies have fully analyzed their association with HIV.
  
  
  OBJECTIVE
  The aim of this study was to analyze circulating levels of sTWEAK and sCD163 as well as other known markers of inflammation (hsCRP, IL-6 and sTNFRII) and endothelial dysfunction (sVCAM-1 and ADMA) in 26 patients with HIV before and after 48 weeks of antiretroviral treatment (ART) and 23 healthy subjects.
  
  
  RESULTS
  Patients with HIV had reduced sTWEAK levels and increased sCD163, sVCAM-1, ADMA, hsCRP, IL-6 and sTNFRII plasma concentrations, as well as increased sCD163/sTWEAK ratio, compared with healthy subjects. Antiretroviral treatment significantly reduced the concentrations of sCD163, sVCAM-1, hsCRP and sTNFRII, although they remained elevated when compared with healthy subjects. Antiretroviral treatment had no effect on the concentrations of ADMA and sTWEAK, biomarkers associated with endothelial function. The use of protease inhibitors as part of antiretroviral therapy and the presence of HCV-HIV co-infection and/or active HIV replication attenuated the ART-mediated decrease in sCD163 plasma concentrations.
  
  
  CONCLUSIONS
  HIV-infected patients showed a proatherogenic profile characterized by increased inflammatory, immune-activation and endothelial-dysfunction biomarkers that partially improved after ART. HCV-HIV co-infection and/or active HIV replication enhanced immune activation despite ART.
authors.affiliation: Instituto de Biomedicina de Sevilla, Hospital Universitario Virgen del Rocío/Centro Superior de Investigaciones Científicas/Universidad de Sevilla, Unidad Clínico-Experimental de Riesgo Vascular, Sevilla, Spain; Unidad Metabólico-Vascular, Fundación de Investigación IdiPAZ-Hospital Universitario La Paz, Madrid, Spain.
authors.forename: Luis M
authors.initials: LM
authors.lastname: Beltrán
authors.affiliation: Instituto de Biomedicina de Sevilla, Hospital Universitario Virgen del Rocío/Centro Superior de Investigaciones Científicas/Universidad de Sevilla, Unidad Clínico-Experimental de Riesgo Vascular, Sevilla, Spain.
authors.forename: Rocío
authors.initials: R
authors.lastname: Muñoz Hernández
authors.affiliation: Laboratorio de Inmunovirología, Unidad Clínica de Enfermedades Infecciosas, Microbiología y Medicina Preventiva, Instituto de Biomedicina de Sevilla, Hospital Universitario Virgen del Rocío/Centro Superior de Investigaciones científicas/Universidad de Sevilla, Sevilla, Spain.
authors.forename: Rebeca S
authors.initials: RS
authors.lastname: de Pablo Bernal
authors.affiliation: Instituto de Biomedicina de Sevilla, Hospital Universitario Virgen del Rocío/Centro Superior de Investigaciones Científicas/Universidad de Sevilla, Unidad Clínico-Experimental de Riesgo Vascular, Sevilla, Spain.
authors.forename: José S
authors.initials: JS
authors.lastname: García Morillo
authors.affiliation: Laboratorio de Patología Vascular, Instituto de Investigación Sanitaria-Fundación Jiménez Díaz, Madrid, Spain; Spanish Biomedical Research Centre in Diabetes and Associated Metabolic Disorders, Madrid, Spain.
authors.forename: Jesús
authors.initials: J
authors.lastname: Egido
authors.affiliation: Laboratorio de Inmunovirología, Unidad Clínica de Enfermedades Infecciosas, Microbiología y Medicina Preventiva, Instituto de Biomedicina de Sevilla, Hospital Universitario Virgen del Rocío/Centro Superior de Investigaciones científicas/Universidad de Sevilla, Sevilla, Spain.
authors.forename: Manuel Leal
authors.initials: ML
authors.lastname: Noval
authors.affiliation: Laboratorio de Inmunovirología, Unidad Clínica de Enfermedades Infecciosas, Microbiología y Medicina Preventiva, Instituto de Biomedicina de Sevilla, Hospital Universitario Virgen del Rocío/Centro Superior de Investigaciones científicas/Universidad de Sevilla, Sevilla, Spain; Laboratorio Inmunobiología Molecular, Hospital General Universitario Gregorio Marañón, Madrid, Spain; Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain; Networking Research Center on Bioengineering, Biomaterials and Nanomedicine, Madrid, Spain.
authors.forename: Sara
authors.initials: S
authors.lastname: Ferrando-Martinez
authors.affiliation: Laboratorio de Patología Vascular, Instituto de Investigación Sanitaria-Fundación Jiménez Díaz, Madrid, Spain.
authors.forename: Luis M
authors.initials: LM
authors.lastname: Blanco-Colio
authors.affiliation: Laboratorio de Inmunovirología, Unidad Clínica de Enfermedades Infecciosas, Microbiología y Medicina Preventiva, Instituto de Biomedicina de Sevilla, Hospital Universitario Virgen del Rocío/Centro Superior de Investigaciones científicas/Universidad de Sevilla, Sevilla, Spain.
authors.forename: Miguel
authors.initials: M
authors.lastname: Genebat
authors.affiliation: Instituto de Biomedicina de Sevilla, Hospital Universitario Virgen del Rocío/Centro Superior de Investigaciones Científicas/Universidad de Sevilla, Unidad Clínico-Experimental de Riesgo Vascular, Sevilla, Spain.
authors.forename: José R
authors.initials: JR
authors.lastname: Villar
authors.affiliation: Instituto de Biomedicina de Sevilla, Hospital Universitario Virgen del Rocío/Centro Superior de Investigaciones Científicas/Universidad de Sevilla, Unidad Clínico-Experimental de Riesgo Vascular, Sevilla, Spain; Department of Vascular Physiopathology, Hospital Nacional de Parapléjicos, Servicio de Salud de Castilla La Mancha, Toledo, Spain.
authors.forename: Rafael
authors.initials: R
authors.lastname: Moreno-Luna
authors.affiliation: Laboratorio de Patología Vascular, Instituto de Investigación Sanitaria-Fundación Jiménez Díaz, Madrid, Spain.
authors.forename: Juan Antonio
authors.initials: JA
authors.lastname: Moreno
mesh_terms: D000328:Adult; D044966:Anti-Retroviral Agents / Q000627:therapeutic use*; D015703:Antigens, CD / Q000097:blood*; D015214:Antigens, Differentiation, Myelomonocytic / Q000097:blood*; D001120:Arginine / Q000031:analogs & derivatives / Q000097:blood; D002097:C-Reactive Protein / Q000032:analysis; D016022:Case-Control Studies; D060085:Coinfection / Q000097:blood* / Q000188:drug therapy; D000074049:Cytokine TWEAK; D005260:Female; D006678:HIV / Q000187:drug effects / Q000302:isolation & purification; D015658:HIV Infections / Q000097:blood* / Q000188:drug therapy*; D016174:Hepacivirus / Q000302:isolation & purification; D006526:Hepatitis C / Q000097:blood*; D006801:Humans; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D008875:Middle Aged; D011956:Receptors, Cell Surface / Q000097:blood*; D048069:Tumor Necrosis Factors / Q000097:blood*; D019010:Vascular Cell Adhesion Molecule-1 / Q000097:blood; D055815:Young Adult; D000098902:CD163 Antigen
chemical_list: D044966:Anti-Retroviral Agents; D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D000098902:CD163 Antigen; D000074049:Cytokine TWEAK; D015850:Interleukin-6; D011956:Receptors, Cell Surface; C109743:TNFSF12 protein, human; D048069:Tumor Necrosis Factors; D019010:Vascular Cell Adhesion Molecule-1; C018524:N,N-dimethylarginine; D002097:C-Reactive Protein; D001120:Arginine