Anti-Inflammatory Interleukin 10 Inversely Relates to Coronary Atherosclerosis in Persons With Human Immunodeficiency Virus.

Interleukin 10 (IL-10) is an anti-inflammatory cytokine that may be protective against coronary atherosclerosis. In an observational study of persons with human immunodeficiency virus (PWH) and uninfected controls, IL-10 was measured in serum samples by means of enzyme-linked immunosorbent assay, and coronary atherosclerosis was assessed using computed tomographic angiography. Among PWH, a 10-fold decrease in IL-10 was associated with a 2.6-fold increase in the odds of coronary plaque (P = .01), after controlling for traditional and nontraditional cardiovascular risk factors. IL-10 was also inversely associated with total coronary plaque (ρ = -0.19; P = .02) and noncalcified coronary plaque (ρ = -0.24; P = .004). Our findings suggest a role for IL-10 in mitigating atherosclerosis in PWH. Clinical Trials Registration. NCT00455793.

Low vitamin D is associated with coronary atherosclerosis in women with HIV.

BACKGROUND: Vitamin D deficiency is underdiagnosed and undertreated, especially among people living with HIV (PLWH). Recently, there has been an increased interest in the role of vitamin D in cardiovascular disease (CVD). While vitamin D deficiency has been associated with CVD in observational studies in the general population, there are limited data in PLWH. We therefore performed an analysis to assess the relationship of vitamin D and coronary atherosclerosis using coronary CT angiography (CCTA). METHODS: Women living with HIV (WLWH) without known CVD were included. Based on the median value of serum vitamin D levels, participants were dichotomized to either the <25 ng/ml (lower vitamin D group) or ≥25 ng/ml (higher vitamin D group). CCTA was used to assess plaque characteristics. RESULTS: Forty-three WLWH were included in the analyses (mean age 46 ±8 years, 56% African American, duration of HIV 15 ±6 years, 83% undetectable HIV viral load). WLWH in the lower vitamin D group (n=22) had significantly higher numbers of segments with any coronary plaque (2.27 ±3.01 versus 0.38 ±0.97; P=0.02) and segments with non-calcified coronary plaque (1.41 ±1.82 versus 0.29 ±0.64; P=0.03) compared with WLWH in the higher vitamin D group (n=21). After adjusting for Framingham CHD risk point score, body mass index, diabetes and race, the relationship remained significant. CONCLUSIONS: Our study demonstrates a significant, independent relationship between lower vitamin D status and higher numbers of noncalcified coronary plaque segments in WLWH. Further studies are warranted to evaluate the effect of vitamin D on CVD in PLWH. Trial Registration Identifier: NCT00455793.

Caspase-1 Activation Is Related With HIV-Associated Atherosclerosis in an HIV Transgenic Mouse Model and HIV Patient Cohort.

OBJECTIVE: Atherosclerotic cardiovascular disease (ASCVD) is an increasing cause of morbidity and mortality in people with HIV since the introduction of combination antiretroviral therapy. Despite recent advances in our understanding of HIV ASCVD, controversy still exists on whether this increased risk of ASCVD is due to chronic HIV infection or other risk factors. Mounting biomarker studies indicate a role of monocyte/macrophage activation in HIV ASCVD; however, little is known about the mechanisms through which HIV infection mediates monocyte/macrophage activation in such a way as to engender accelerated atherogenesis. Here, we experimentally investigated whether HIV expression is sufficient to accelerate atherosclerosis and evaluated the role of caspase-1 activation in monocytes/macrophages in HIV ASCVD. Approach and Results: We crossed a well-characterized HIV mouse model, Tg26 mice, which transgenically expresses HIV-1, with ApoE-/- mice to promote atherogenic conditions (Tg26+/-/ApoE-/-). Tg26+/-/ApoE-/- have accelerated atherosclerosis with increased caspase-1 pathway activation in inflammatory monocytes and atherosclerotic vasculature compared with ApoE-/-. Using a well-characterized cohort of people with HIV and tissue-banked aortic plaques, we documented that serum IL (interleukin)-18 was higher in people with HIV compared with non-HIV-infected controls, and in patients with plaques, IL-18 levels correlated with monocyte/macrophage activation markers and noncalcified inflammatory plaques. In autopsy-derived aortic plaques, caspase-1+ cells and CD (clusters of differentiation) 163+ macrophages correlated. CONCLUSIONS: These data demonstrate that expression of HIV is sufficient to accelerate atherogenesis. Further, it highlights the importance of caspase-1 and monocyte/macrophage activation in HIV atherogenesis and the potential of Tg26+/-/ApoE-/- as a tool for mechanistic studies of HIV ASCVD.

Gastrointestinal Barrier Breakdown and Adipose Tissue Inflammation.

PURPOSE OF REVIEW: Obesity is a state of chronic inflammation. This review aims to summarize recent data supporting the role of the intestinal mucosal barrier and the microbiome in causing adipose tissue inflammation as well as metabolic factors that can affect the intestinal barrier. RECENT FINDINGS: Obesity and its metabolic consequences, such as diabetes mellitus, are associated with disruption of the intestinal barrier function. Intestinal microbiota and diet play a key role in the maintenance of a healthy intestinal epithelium. Intestinal barrier dysfunction can lead to heightened inflammation, which in turn can further damage the intestinal barrier through the disruption of tight junction proteins. Intestinal barrier breakdown is associated with adipose tissue inflammation in different disease states, such as obesity, diabetes mellitus, HIV, and inflammatory bowel disease. Future therapeutic strategies to ameliorate intestinal barrier function may help reduce inflammation in obesity and other chronic conditions of increased intestinal permeability.

Mild renal impairment is associated with calcified plaque parameters assessed by computed tomography angiography in people living with HIV.

OBJECTIVE: To investigate the association of mild renal impairment and coronary plaque in people living with HIV (PLHIV). METHODS: PLHIV and non-HIV controls with serum creatinine less than 1.5 mg/dl were investigated. Estimated glomerular filtration rate (eGFR) (calculated by CKD-EPI formula) was related to coronary plaque indices obtained by CT angiography. RESULTS: One hundred and eighty-four PLHIV [HIV viral load, 49 (47,49) copies/ml, CD4+ cell count, median 536 (370, 770) cells/µl, duration HIV, 15 ±â€Š7 years] and 72 HIV-negative controls without known cardiovascular disease (CVD) were studied. The two groups were well matched for traditional CVD risk factors. Serum creatinine (0.9 ±â€Š0.2 vs. 0.9 ±â€Š0.2 mg/dl, P = 0.96) and eGFR (96 ±â€Š22 vs. 96 ±â€Š24 ml/min per 1.73 m(2), P = 0.99) were similar between PLHIV and non-HIV, respectively. In PLHIV, eGFR inversely related to total severity of coronary plaque score (r = -0.27, P = 0.002), total coronary segments with plaque (r = -0.21, P = 0.005), calcified plaque segments (r = -0.15, P = 0.045), and Agatston score (r = -0.21, P = 0.006). Adjusting for total Framingham point score, BMI, and HIV parameters, eGFR remained significantly associated with calcified plaque and Agatston score in PLHIV. In HIV negative controls, eGFR did not correlate with calcified plaque (r = -0.20, P = 0.10) or Agatston score (r = -0.13, P = 0.29). Among PLHIV, those with eGFR less than 90 ml/min per 1.73 m(2) demonstrated increased total severity of coronary plaque score compared with those with eGFR greater than or equal to 90, P = 0.02). This relationship was stronger in PLHIV than the non-HIV group. CONCLUSION: Our data highlight a robust relationship between subclinical renal impairment and coronary artery disease among PLHIV. Further research is needed to understand the relationship between mild renal impairment and CVD in HIV.

I-FABP Is Higher in People With Chronic HIV Than Elite Controllers, Related to Sugar and Fatty Acid Intake and Inversely Related to Body Fat in People With HIV.

BACKGROUND: Intestinal fatty acid binding protein (I-FABP) has been shown to be a marker of intestinal damage among people living with HIV. We hypothesized that I-FABP would be increased in chronically HIV-infected patents more than elite controllers and would relate to specific nutrient intake and body composition. METHODS: In an observational study, serum I-FABP was measured by enzyme-linked immunosorbent assay. Anthropometric measurements, dual-energy x-ray absorptiometry, and single-slice abdominal computed tomography were obtained to assess body composition, as well as visceral and subcutaneous adipose tissue areas (VAT and SAT). Dietary intake was assessed using 4-day food records. RESULTS: One hundred forty-nine people with chronic HIV (65% male, 47 ± 7 years of age, 54.7% white, and 14 ± 6 years of known HIV), 10 elite controllers (60% male, 53 ± 8 years, 60% white, and 20 ± 7 years of known HIV), and 69 HIV-negative controls (59.4% male, 46 ± 7 years, and 52.2% white) were included in the analysis. I-FABP was significantly higher in HIV progressors relative to HIV-negative controls and elite controllers. In the chronic HIV group, I-FABP was positively associated with dietary intake of added sugar and with saturated fatty acids. I-FABP was inversely associated with body mass index, VAT, and SAT. I-FABP also correlated with MCP-1, CXCL10, sCD163, and lipopolysaccharide (LPS) among all participants. CONCLUSIONS: I-FABP was increased among chronically HIV-infected patients to a greater degree than in elite controllers and was related to nutrient intake and body composition in HIV progressors. Future studies to investigate the role of intestinal damage on nutrient absorption are needed to elucidate the mechanisms of these relationships. TRIAL REGISTRATION IDENTIFIER: NCT00455793.

The IC(50) of anti-Pfs25 antibody in membrane-feeding assay varies among species.

Plasmodium falciparum surface protein 25 (Pfs25) is a candidate for transmission-blocking vaccines (TBVs). Anti-Pfs25 antibodies block the development of oocysts in membrane-feeding assays and we have shown the activity correlates with antibody titer. In this study, we purified Pfs25-specific IgGs to convert antibody titer to microg/mL and determined the amount of antibody required to inhibit 50% of oocyst development (IC(50)). The IC(50) were, 15.9, 4.2, 41.2, and 85.6microg/mL for mouse, rabbit, monkey and human, respectively, and the differences among species were significant. Anti-Pfs25 sera from rabbit, monkey and human showed different patterns of competition against 6 mouse monoclonal antibodies, and the avidity of antibodies among four species were also different. These data suggests that information obtained from animal studies which assess efficacy of TBV candidates may be difficult to translate to human immunization.