Parallel increase of subclinical atherosclerosis and epicardial adipose tissue in patients with HIV.

BACKGROUND: Epicardial adipose tissue (EAT) may contribute to the development of coronary atherosclerosis via paracrine secretion of inflammatory cytokines. METHODS: This is a prospective, observational study of 240 consecutive HIV-infected patients receiving antiretroviral therapy. All patients underwent 2 sequential chest computed tomographic scans to assess the change in coronary artery calcium (CAC), a marker of subclinical atherosclerosis, and EAT volume. Patients with known cardiovascular disease were excluded. Factors independently associated with EAT change were explored using multivariable linear regression analyses. The association between EAT increase and CAC progression was explored using logistic regression analyses. RESULTS: Two hundred forty patients were included. Patients' mean age was 47.5 ± 8 years, and 68% were men. The median interval between computed tomographic scans was 18.7 months (interquartile range 10-27 months). Men showed a larger increase in EAT (5 ± 14.2 cm(3)) than did women (-0.45 ± 8.8 cm(3), P = .007). Factors independently associated with change in EAT were CD4(+) recovery (ß = 0.43, CI 0.05-0.82) and male gender (ß = 5.65, CI, 1.05-10.26). Change in EAT was independently associated with CAC progression (odds ratio 1.04, 95% CI 1.004-1.88, P = .030) after adjusting for traditional cardiovascular risk factors. CONCLUSIONS: In this cohort of patients with HIV receiving antiretroviral therapy, male gender and CD4(+) were independent predictors of EAT increase, and there was a parallel progression of CAC and EAT. Abnormal immunoreactivity associated with T-lymphocyte recovery should be further studied as a determinant of atherosclerosis progression in HIV-infected patients.

Cost of noninfectious comorbidities in patients with HIV.

OBJECTIVES: We hypothesized that the increased prevalence of noninfectious comorbidities (NICMs) observed among HIV-infected patients may result in increased direct costs of medical care compared to the general population. Our objective was to provide estimates of and describe factors contributing to direct costs for medical care among HIV-infected patients, focusing on NICM care expenditure. METHODS: A case-control study analyzing direct medical care costs in 2009. Antiretroviral therapy (ART)-experienced HIV-infected patients (cases) were compared to age, sex, and race-matched adults from the general population, included in the CINECA ARNO database (controls). NICMs evaluated included cardiovascular disease, hypertension, diabetes mellitus, bone fractures, and renal failure. Medical care cost information evaluated included pharmacy, outpatient, and inpatient hospital expenditures. Linear regression models were constructed to evaluate predictors of total care cost for the controls and cases. RESULTS: There were 2854 cases and 8562 controls. Mean age was 46 years and 37% were women. We analyzed data from 29,275 drug prescription records. Positive predictors of health care cost in the overall population: HIV infection (ß = 2878; confidence interval (CI) = 2001-3755); polypathology (ß = 8911; CI = 8356-9466); age (ß = 62; CI = 45-79); and ART exposure (ß = 18,773; CI = 17,873-19,672). Predictors of health care cost among cases: Center for Disease Control group C (ß = 1548; CI = 330-2766); polypathology (ß = 11,081; CI = 9447-12,716); age < 50 years (ß = 1903; CI = 542-3264); protease inhibitor exposure (per month of use; ß = 69; CI = 53-85); CD4 count < 200 cells/mm(3) (ß = 5438; CI = 3082-7795); and ART drug change (per change; ß = 911; CI = 716-1106). CONCLUSION: Total cost of medical care is higher in cases than controls. Lower medical costs associated with higher CD4 strata are offset by increases in the care costs needed for advancing age, particularly for NICMs.

Ectopic fat is linked to prior cardiovascular events in men with HIV.

Epicardial Adipose Tissue (EAT) has been associated with adverse cardiovascular events in the general population. We studied the association of general adiposity measures (body mass index, waist circumference) and ectopic adipose tissue [visceral adipose tissue (VAT); liver fat (LF); EAT) with prevalent cardiovascular disease (CVD) (prior myocardial infarction, coronary revascularization, stroke, peripheral vascular disease] in 583 HIV-infected men. VAT, EAT, and LF (liver/spleen attenuation ratio < 1.1) were measured by computed tomography. Patients' mean age was 48.5 ± 8.1 years, prior CVD was present in 33 (5.7%) patients. Factors independently associated with CVD on multivariable analyses were age [incidence-rate ratio (IRR) = 1.07, 95% confidence interval (CI): 1.02 to 1.12], smoking (IRR = 2.70, 95% CI: 1.22 to 6.01), Center for Disease Control group C (IRR = 3.09, 95% CI: 1.41 to 6.76), EAT (IRR = 1.13, 95% CI: 1.04 to 1.24, per 10 cm), LF (IRR = 1.17, 95% CI: 1.04 to 1.32), and VAT (IRR = 1.05, 95% CI: 1.00 to 1.10, per 10 cm). Ectopic fat but not general adiposity measures were associated with prevalent CVD in men with HIV.

Morphological and metabolic components of lipodystrophy in various nevirapine-based highly active antiretroviral therapy (HAART) regimens: a cross-sectional, observational study.

BACKGROUND: Morphological abnormalities (lipoatrophy and central fat accumulation) and metabolic changes (dyslipidaemia and glucose regulation impairment) have emerged as components of lipodystrophy and as major tolerability issues with long-term use of highly active antiretroviral therapy (HAART) in HIV-positive patients. Protease inhibitors (PIs) are recognized as having the greatest impact in terms of metabolic complications, followed by nucleoside reverse transcriptase inhibitors, while the non-nucleoside reverse transcriptase inhibitors (NNRTIs) have the least impact. In particular, regimens based on the NNRTI nevirapine have been shown to achieve significant metabolic benefits and may help to improve dyslipidaemia. Improvements in body shape changes associated with lipodystrophy have also been reported when nevirapine replaced a PI in long-term triple therapy. OBJECTIVE: The objective of this cross-sectional observational ('real-world') study was to investigate the effect of three HAART regimens plus stable nevirapine therapy on morphological and metabolic components of lipodystrophy in HIV-infected patients. METHODS: Consecutive patients (aged >18 years) with serologically documented HIV infection, who had received HAART for at least 2 years and who had been diagnosed with lipodystrophy, were followed up as outpatients at the metabolic clinic of the University of Modena and Reggio Emilia, Modena, Italy. Patients received stable nevirapine therapy plus fixed-dose combinations of tenofovir disoproxil fumarate plus emtricitabine (Truvada(®); TVD), zidovudine plus lamivudine (3TC) [Combivir(®); CBV], or abacavir plus lamivudine (Kivexa(®); KVX). Multivariate regression analyses were performed to analyse predictors of four components of lipodystrophy: lipoatrophy using leg fat mass measured by dual-emission x-ray absorptiometry (DXA), fat accumulation using waist circumference, dyslipidaemia using apolipoprotein (Apo)B/ApoA1 ratio, and glucose intolerance using the Homeostasis Model Assessment for Insulin Resistance (HOMA-IR). RESULTS: Overall, 101 patients were enrolled (TVD group = 61, CBV group = 20, KVX group = 20); 191 observations were analysed. Male sex was associated with reduced leg fat mass, while age and body mass index (BMI) were associated with increased leg fat mass (all p < 0.05). Leg fat mass and male sex were associated with increased waist circumference (p < 0.001 for both). Leg fat mass predicted reduced ApoB/ApoA1 ratio, while age and BMI predicted increased ApoB/ApoA1 ratio (all p < 0.05). BMI predicted HOMA-IR increase (p = 0.0017). No differences in lipoatrophy, central fat accumulation, dyslipidaemia or glucose metabolism were observed among any of the three different nevirapine plus nucleoside backbone groups (TVD, CBV or KVX). CONCLUSION: HAART including nevirapine has a limited impact on components of lipodystrophy in patients with HIV infection. Further studies are needed to verify if nevirapine overcomes the expected distinct lipodystrophy risk profile associated with different nucleoside backbone therapies.

Epicardial adipose tissue is an independent marker of cardiovascular risk in HIV-infected patients.

BACKGROUND: Epicardial adipose tissue (EAT) is increased in HIV-infected patients. The aim of this study was to evaluate the association between EAT and coronary artery calcium (CAC) a marker of atherosclerosis; furthermore, we investigated the association of EAT with HIV infection, antiretroviral therapy (ART), and lipodystrophy. METHODS: This was a cross-sectional study of 876 consecutive HIV-infected ART experienced patients. Patients underwent CAC imaging with multidetector computed tomography (CT) for atherosclerosis screening and risk of cardiovascular events (CAC score >100); EAT was measured in the same CT images. Factors independently associated with EAT were explored in a multivariable backward stepwise linear regression analysis. Multivariable logistic regression was used to evaluate the association of EAT and CAC score greater than 100. RESULTS: Patients' mean age was 47.2 ± 8 years, 68% were men. EAT was associated with central fat accumulation and mixed lipodystrophy phenotypes. Factors independently associated with EAT were: age [ß = 0.6, confidence interval (CI) 0.2-1.0], male sex (ß = 6.6, CI 0.5-12.7), visceral adipose tissue (ß = 0.12, CI 0.08-0.17), waist circumference (ß = 0.7, CI 0.04-1.3), current CD4⁺ (ß = 0.6, CI 0.1-1.2, per 50 cells), total cholesterol (ß = 0.1, CI 0.02-0.15), and cumulative exposure to ART (months) (ß = 0.05, CI 0.00-0.11). EAT (per 10 cm³) was associated with CAC greater than 100 (odds ratio = 1.10, CI 1.02-1.19) after adjustment for age, male sex, and diabetes. CONCLUSION: We showed an association between EAT and central fat accumulation and mixed form lipodystrophy phenotypes as well as traditional risk factors for atherosclerosis. EAT may be a useful marker of cardiovascular risk as shown by its association with CAC greater than 100.

Hypertriglyceridemia and waist circumference predict cardiovascular risk among HIV patients: a cross-sectional study.

BACKGROUND: Although half of HIV-infected patients develop lipodystrophy and metabolic complications, there exists no simple clinical screening tool to discern the high from the low-risk HIV-infected patient. Thus, we evaluated the associations between waist circumference (WC) combined with triglyceride (TG) levels and the severity of lipodystrophy and cardiovascular risk among HIV-infected men and women. METHODS: 1481 HIV-infected men and 841 HIV-infected women were recruited between 2005 and 2009 at the metabolic clinic of the University of Modena and Reggio Emilia in Italy. Within each gender, patients were categorized into 4 groups according to WC and TG levels. Total and regional fat and fat-free mass were assessed by duel-energy x-ray absorptiometry, and visceral adipose tissue (VAT) and abdominal subcutaneous AT (SAT) were quantified by computed tomography. Various cardiovascular risk factors were assessed in clinic after an overnight fast. RESULTS: The high TG/high WC men had the most VAT (208.0 ± 94.4 cm(2)), as well as the highest prevalence of metabolic syndrome (42.2%) and type-2 diabetes (16.2%), and the highest Framingham risk score (10.3 ± 6.5) in comparison to other groups (p<0.05 for all). High TG/high WC women also had elevated VAT (150.0 ± 97.9 cm(2)) and a higher prevalence of metabolic syndrome (53.3%), hypertension (30.5%) and type-2 diabetes (12.0%), and Framingham risk score(2.9 ± 2.8) by comparison to low TG/low WC women (p<0.05 for all). CONCLUSIONS: A simple tool combining WC and TG levels can discriminate high- from low-risk HIV-infected patients.