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

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 ART-treated, virologically-suppressed and immune-reconstituted patients.

METHODS.: The patients were evaluated for clinical LD, VAT, SAT, insulin resistance (HOMA-IR) and coronary calcium score (CAC>10). T-cell activation (CD8/CD38), differentiation (CD4/CD8/CCR7/CD45RA) and expression/activation of the IL7/IL-7R system (CD4/CD8/CD127; IL-7; 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: ß=5.63; p=0.005; and: ß=4.19; p=0.020). This was also the case for IL-7R expressing CD8+T-cells (CD127+): respectively for lipoatrophy ß=12.8; p=0.003 and central fat accumulation ß=9.45; p=0.016. CD8+T-cell activation was also associated with VAT/TAT (ß= 0.01; p=0.002) and SAT/VAT ratios (ß= -0.014; p=0.015).As expected, VAT/TAT was an independent risk factor for insulin resistance (HOMA-IR, r=0.364, p=0.028) and cardiovascular risk (CAC, r=0.406, p=0.002).

CONCLUSIONS.: CD8+T-cell activation was associated with lipodystrophy and the relative amount of VAT in ART-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 cardio-metabolic risk.