18FDG PET-CT imaging detects arterial inflammation and early atherosclerosis in HIV-infected adults with cardiovascular disease risk factors

BACKGROUND: Persistent vascular inflammation has been implicated as an important cause for a higher prevalence of cardiovascular disease (CVD) in HIV-infected adults. In several populations at high risk for CVD, vascular (18)Fluorodeoxyglucose ((18)FDG) uptake quantified using 3D-positron emission-computed tomography (PET-CT) has been used as a molecular level biomarker for the presence of metabolically active proinflammatory macrophages in rupture-prone early atherosclerotic plaques. We hypothesized that (18)FDG PET-CT imaging would detect arterial inflammation and early atherosclerosis in HIV-infected adults with modest CVD risk. METHODS: We studied 9 HIV-infected participants with fully suppressed HIV viremia on antiretroviral therapy (8 men, median age 52 yrs, median BMI 29 kg/m(2), median CD4 count 655 cells/μL, 33% current smokers) and 5 HIV-negative participants (4 men, median age 44 yrs, median BMI 25 kg/m(2), no current smokers). Mean Framingham Risk Scores were higher for HIV-infected persons (9% vs. 2%, p < 0.01). (18)FDG (370 MBq) was administered intravenously. 3D-PET-CT images were obtained 3.5 hrs later. (18)FDG uptake into both carotid arteries and the aorta was compared between the two groups. RESULTS: Right and left carotid (18)FDG uptake was greater (P < 0.03) in the HIV group (1.77 ±0.26, 1.33 ±0.09 target to background ratio (TBR)) than the control group (1.05 ± 0.10, 1.03 ± 0.05 TBR). (18)FDG uptake in the aorta was greater in HIV (1.50 ±0.16 TBR) vs control group (1.24 ± 0.05 TBR), but did not reach statistical significance (P = 0.18). CONCLUSIONS: Carotid artery (18)FDG PET-CT imaging detected differences in vascular inflammation and early atherosclerosis between HIV-infected adults with CVD risk factors and healthy HIV-seronegative controls. These findings confirm the utility of this molecular level imaging approach for detecting and quantifying glucose uptake into inflammatory macrophages present in metabolically active, rupture-prone atherosclerotic plaques in HIV infected adults; a population with increased CVD risk

Exercise training augments the peripheral insulin-sensitizing effects of pioglitazone in HIV-infected adults with insulin resistance and central adiposity

The prevalence and incidence of insulin resistance and type 2 diabetes mellitus (DM) are higher in people treated for human immunodeficiency virus-1 (HIV) infection than in the general population. Identifying safe and effective interventions is a high priority. We evaluated whether the peroxisome proliferator-activated receptor-γ agonist pioglitazone with exercise training improves central and peripheral insulin sensitivity more than pioglitazone alone in HIV-infected adults with insulin resistance and central adiposity. Forty-four HIV-infected adults with baseline insulin resistance and central adiposity were randomly assigned to 4 mo of pioglitazone (30 mg/day) with or without supervised, progressive aerobic, and resistance exercise training (1.5–2 h/day, 3 days/wk). The hyperinsulinemic euglycemic clamp was used to evaluate alterations in central and peripheral insulin sensitivity. Thirty-nine participants completed the study. Hepatic insulin sensitivity improved similarly in both groups. Exercise training augmented the beneficial effects of pioglitazone on peripheral insulin sensitivity. Greater improvements in peripheral insulin sensitivity were associated with reductions in total body and limb adipose content rather than increases in limb adiposity or pioglitazone-induced increases in adiponectin concentration. We conclude that supplementing pioglitazone with increased physical activity improved insulin sensitivity more effectively than pioglitazone alone in HIV-infected adults with insulin resistance and central adiposity. Pioglitazone alone did not significantly increase limb adipose content. Potential cardiovascular benefits of these interventions in HIV need investigation