title: TNF-α levels in HIV-infected patients after long-term suppressive cART persist as high as in elderly, HIV-uninfected subjects.
abstract: BACKGROUND
  Chronic and systemic inflammatory alterations occur in HIV-infected patients and elderly uninfected subjects and in both scenarios these alterations are associated with the development of chronic morbidities and mortality. However, whether the levels of inflammatory alterations in untreated HIV-infected patients and elderly individuals are similar is unknown. Moreover, whether long-term antiretroviral therapy normalizes inflammatory alterations compared with HIV-uninfected persons of different age is not known.
  
  
  METHODS
  We analysed soluble inflammatory levels [high-sensitivity C-reactive protein, interferon (IFN)-γ, tumour necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, IL-8 and IL-17] in a cohort of viraemic HIV-infected patients compared with (i) age-matched, (ii) elderly and (iii) non-survivor elderly, uninfected healthy controls. We longitudinally analysed the effect of long-term 48 and 96 week suppressive combined antiretroviral therapy (cART) on the soluble inflammatory levels compared with those found in control subjects.
  
  
  RESULTS
  Baseline IL-6 and IL-8 levels were at similar or lower concentrations in untreated patients compared with healthy elderly individuals. However, TNF-α and IFN-γ levels broadly exceeded those found in survivors and non-survivor elderly individuals. Long-term suppressive cART normalized most of the inflammatory markers, with the exception of TNF-α levels, which persisted as high as those in elderly non-survivor controls.
  
  
  CONCLUSIONS
  Chronic inflammatory alterations associated with HIV infection are maintained at a different level from those of ageing. The persistent alteration of TNF-α levels in HIV-infected patients might cause tissue damage and have implications for developing non-AIDS-defining illnesses, even when HIV replication is long-term controlled by cART.
authors.affiliation: Laboratory of Immunovirology, Clinic Unit of Infectious Diseases, Microbiology and Preventive Medicine, Institute of Biomedicine of Seville, IBiS, Virgen del Rocío University Hospital/CSIC/University of Seville, Seville, Spain.
authors.forename: R S
authors.initials: RS
authors.lastname: De Pablo-Bernal
authors.affiliation: Laboratory of Immunovirology, Clinic Unit of Infectious Diseases, Microbiology and Preventive Medicine, Institute of Biomedicine of Seville, IBiS, Virgen del Rocío University Hospital/CSIC/University of Seville, Seville, Spain.
authors.forename: E
authors.initials: E
authors.lastname: Ruiz-Mateos
authors.affiliation: Laboratory of Immunovirology, Clinic Unit of Infectious Diseases, Microbiology and Preventive Medicine, Institute of Biomedicine of Seville, IBiS, Virgen del Rocío University Hospital/CSIC/University of Seville, Seville, Spain.
authors.forename: I
authors.initials: I
authors.lastname: Rosado
authors.affiliation: Laboratory of Immunovirology, Clinic Unit of Infectious Diseases, Microbiology and Preventive Medicine, Institute of Biomedicine of Seville, IBiS, Virgen del Rocío University Hospital/CSIC/University of Seville, Seville, Spain.
authors.forename: B
authors.initials: B
authors.lastname: Dominguez-Molina
authors.affiliation: Department of Clinical Biochemistry, Institute of Biomedicine of Seville, IBiS, Virgen del Rocío University Hospital IBiS/CSIC/University of Seville, Seville, Spain.
authors.forename: A I
authors.initials: AI
authors.lastname: Alvarez-Ríos
authors.affiliation: Department of Medical Biochemistry and Molecular Biology and Immunology, University of Seville School of Medicine, Institute of Biomedicine of Seville, IBiS, Virgen del Rocío University Hospital/CSIC/University of Seville and Red Temática de Investigación Cooperativa en Envejecimiento y Fragilidad (RETICEF)-Instituto de Salud Carlos III, Seville, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Carrillo-Vico
authors.affiliation: Internal Medicine Service, San Juan de Dios Hospital, Bormujos, Seville, Spain.
authors.forename: R
authors.initials: R
authors.lastname: De La Rosa
authors.affiliation: Laboratory of Molecular Immuno-Biology, Hospital General Universitario Gregorio Marañón, Madrid, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Delgado
authors.affiliation: Laboratory of Molecular Immuno-Biology, Hospital General Universitario Gregorio Marañón, Madrid, Spain.
authors.forename: M A
authors.initials: MA
authors.lastname: Muñoz-Fernández
authors.affiliation: Laboratory of Immunovirology, Clinic Unit of Infectious Diseases, Microbiology and Preventive Medicine, Institute of Biomedicine of Seville, IBiS, Virgen del Rocío University Hospital/CSIC/University of Seville, Seville, Spain mleal@telefonica.net.
authors.forename: M
authors.initials: M
authors.lastname: Leal
authors.affiliation: Laboratory of Molecular Immuno-Biology, Hospital General Universitario Gregorio Marañón, Madrid, Spain.
authors.forename: S
authors.initials: S
authors.lastname: Ferrando-Martínez
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D044966:Anti-Retroviral Agents / Q000008:administration & dosage*; D015331:Cohort Studies; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D015658:HIV Infections / Q000097:blood* / Q000188:drug therapy*; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D012189:Retrospective Studies; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000097:blood*
chemical_list: D044966:Anti-Retroviral Agents; D014409:Tumor Necrosis Factor-alpha
keywords: HIV infection; ageing; inflammation