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CD8 T-Cell Activation Is Associated With Lipodystrophy and Visceral Fat Accumulation in Antiretroviral Therapy–Treated Virologically Suppressed HIV-Infected Patients

Guaraldi, Giovanni MD*; Luzi, Kety MD; Bellistrì, Giusi Maria MD; Zona, Stefano MD*; Domingues da Silva, Ana Rita MD; Bai, Francesca MD; Garlassi, Elisa MD*; Marchetti, Giulia MD,PhD; Capeau, Jacqueline MD, PhD§; d’Arminio Monforte, Antonella MD

JAIDS Journal of Acquired Immune Deficiency Syndromes: 1 December 2013 - Volume 64 - Issue 4 - p 360–366
doi: 10.1097/QAI.0000000000000001
Clinical Science

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.

Design: 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.

*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.

Correspondence to: Giovanni Guaraldi, MD, Department of Medical and Surgical Sciences for Adults and Children, Clinic of Infectious Diseases, University of Modena and Reggio Emilia, Largo del pozzo, 71 41100 Modena, Italy (e-mail: giovanni.guaraldi@unimore.it).

The authors have no funding or conflicts of interest to disclose.

A.R.D.d.S. prepared the data set. G.G., A.d'A.M., and G.M. developed the concept of this study. G.M.B. performed the immunologic assay and the data entry. F.B. and S.Z. carried out the statistical analysis. K.L., G.G., and J.C. wrote the manuscript. All authors read and approved the final manuscript.

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Received March 26, 2013

Accepted September 09, 2013

© 2013 by Lippincott Williams & Wilkins