title: CD8 T-cell activation is associated with lipodystrophy and visceral fat accumulation in antiretroviral therapy-treated virologically suppressed HIV-infected patients.
abstract: OBJECTIVE
  HIV-infected patients receiving antiretroviral treatment frequently accumulate fat at the abdominal level. It is unknown whether T-cell activation and immune phenotypes are associated with fat accumulation. Thus, the aim of the study was to search for an association between the presence of clinical lipodystrophy (LD), visceral and subcutaneous abdominal adipose tissue amount (VAT and SAT), and peripheral T-cell immune phenotypes.
  
  
  METHODS
  Cross-sectional study including 87 HIV-infected antiretroviral therapy-treated virologically suppressed and immune-reconstituted patients.
  
  
  METHODS
  The patients were evaluated for clinical LD, VAT, SAT, homeostasis model of insulin resistance, and coronary artery calcium score (>10). T-cell activation (CD8/CD38), differentiation (CD4/CD8/CCR7/CD45RA), and expression/activation of the interleukin-7 (IL-7)/IL-7R system (CD4/CD8/CD127, IL-7, and CD4/CD8/pStat-5) were assessed by cytometry.
  
  
  RESULTS
  In multivariable analyses, CD8 T-cell activation (CD38) was associated with lipoatrophy and central fat accumulation (respectively, β = 5.63, P = 0.005, and β = 4.19, P = 0.020). This was also the case for IL-7R expressing CD8⁺ T cells (CD127⁺) for lipoatrophy β = 12.8, P = 0.003, and for central fat accumulation β = 9.45, P = 0.016. CD8⁺ T-cell activation was also associated with VAT/total adipose tissue (β = 0.01, P = 0.002) and SAT/VAT ratios (β = -0.014, P = 0.015). As expected, VAT/total adipose tissue was an independent risk factor for homeostasis model of insulin resistance (r = 0.364, P = 0.028) and cardiovascular risk (coronary artery calcium, r = 0.406, P = 0.002).
  
  
  CONCLUSIONS
  CD8⁺ T-cell activation was associated with LD and the relative amount of VAT in antiretroviral therapy-controlled, virologically suppressed, HIV-infected patients. We propose that CD8 activation may be involved in the accumulation of central fat frequently observed in these patients, with resulting increased cardiometabolic risk.
authors.affiliation: *Department of Medical and Surgical Sciences for Adults and Children, Clinic of Infectious Diseases, University of Modena and Reggio Emilia, Modena, Italy; †Department of Medicine, Surgery and Dentistry, Clinic of Infectious and Tropical Diseases, University of Milano, Milan, Italy; ‡Serviço de Doenças Infecciosas, Hospital de Joaquim Urbano, Porto, Portugal; and §Biochimie et Hormonologie, Hôpital Tenon AP-HP Paris, CDR Saint-Antoine, Inserm U938, Université Paris6-UPMC, Faculté de Médecine Pierre et Marie Curie, Paris, France.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Guaraldi
authors.forename: Kety
authors.initials: K
authors.lastname: Luzi
authors.forename: Giusi Maria
authors.initials: GM
authors.lastname: Bellistrì
authors.forename: Stefano
authors.initials: S
authors.lastname: Zona
authors.forename: Ana Rita
authors.initials: AR
authors.lastname: Domingues da Silva
authors.forename: Francesca
authors.initials: F
authors.lastname: Bai
authors.forename: Elisa
authors.initials: E
authors.lastname: Garlassi
authors.forename: Giulia
authors.initials: G
authors.lastname: Marchetti
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Capeau
authors.forename: Antonella d'Arminio
authors.initials: Ad
authors.lastname: Monforte
mesh_terms: D000273:Adipose Tissue; D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D018414:CD8-Positive T-Lymphocytes / Q000502:physiology*; D003430:Cross-Sectional Studies; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D039682:HIV-Associated Lipodystrophy Syndrome / Q000378:metabolism*; D006801:Humans; D008213:Lymphocyte Activation / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D010766:Phosphorylation; D050799:STAT5 Transcription Factor / Q000235:genetics / Q000378:metabolism; D019562:Viral Load; D014766:Viremia
chemical_list: D019380:Anti-HIV Agents; D050799:STAT5 Transcription Factor