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ObjectiveThe aim of this study was to assess the association of cardiovascular disease (CVD) risk scores and coronary artery plaque (CAP) progression in HIV-infected participants.MethodsWe studied men with and without HIV-infection enrolled in the Multicenter AIDS Cohort Study (MACS) CVD study. CAP at baseline and follow-up was assessed with cardiac computed tomography angiography (CCTA). We examined the association between baseline risk scores including pooled cohort equation (PCE), Framingham risk score (FRS), and Data collect of Adverse effects of anti-HIV drugs equation (D:A:D) and CAP progression.ResultsWe studied 495 men (211 HIV-uninfected, 284 HIV-infected). The adjusted odds ratio (aOR) of total plaque volume (TPV) and noncalcified plaque volume (NCPV) progression in the highest relative to lowest tertile was 9.4 [95% confidence interval (95% CI) 2.4-12.1, P

Background and aimsPeople living with HIV (HIV+) are surviving longer due to effective antiretroviral therapy. Cardiovascular disease is a leading cause of non-AIDS related clinical events. We determined HIV-related factors associated with coronary artery stenosis progression.MethodsWe performed serial coronary CT angiography among HIV+ and HIV-uninfected (HIV-) men in the Multicenter AIDS Cohort Study. The median inter-scan interval was 4.5 years. Stenosis was graded as 0, 1-29, 30-49, 50-69 or ≥70%. Progression was defined as an increase ≥2 categories. Suppressed HIV infection was consistent viral loads 1 viral load >500 copies/ml demonstrated greatest stenosis progression (RR 3.01; 95% CI, 1.53-4.92, p=0.001 compared with HIV- men). Suppressed HIV+men with suboptimal antiretroviral adherence had greater stenosis progression (RR 1.91; 95% CI 1.12-3.24, p=0.02) than HIV+suppressed men with optimal adherence.ConclusionsCoronary artery stenosis progression was associated with suboptimal HIV RNA suppression and antiretroviral therapy adherence. Effective ongoing HIV virologic suppression and antiretroviral therapy adherence may mitigate risk for coronary disease events among people living with HIV.

Background People with HIV are disproportionately coinfected with hepatitis C virus (HCV) and experience accelerated liver-related mortality. Direct-acting antivirals (DAAs) yield high sustained virologic response (SVR) rates, but uptake is suboptimal. This study characterizes the DAA-era HCV treatment cascade and barriers among US men and women with or at risk for HIV. Methods We constructed HCV treatment cascades using the Women’s Interagency HIV Study (women, 6 visits, 2015–2018, n = 2447) and Multicenter AIDS Cohort Study (men, 1 visit, 2015–2018, n = 2221). Cascades included treatment-eligible individuals (ie, HCV RNA-positive or reported DAAs). Surveys captured self-reported clinical (eg, CD4), patient (eg, missed visits), system (eg, appointment access), and financial/insurance barriers. Results Of 323/92 (women/men) treatment eligible, most had HIV (77%/70%); 69%/63% were black. HIV-positive women were more likely to attain cascade outcomes than HIV-negative women (39% vs 23% initiated, 21% vs 12% SVR); similar discrepancies were noted for men. Black men and substance users were treated less often. Women initiating treatment (vs not) reported fewer patient barriers (14%/33%). Among men not treated, clinical barriers were prevalent (53%). Conclusions HIV care may facilitate HCV treatment linkage and barrier navigation. HIV-negative individuals, black men, and substance users may need additional support. Clinical trials registration NCT00000797 (Women’s Interagency HIV Study); NCT00046280 (Multicenter AIDS Cohort Study).

Background The purpose of this study is to determine if a new score calculated with coronary artery calcium (CAC) density and volume is associated with total coronary artery plaque burden and composition on coronary CT angiography (CCTA) compared to the Agatston score (AS). Methods We identified 347 men enrolled in the Multicenter AIDS cohort study who underwent contrast and non-contrast CCTs, and had CAC>0. CAC densities (mean Hounsfield Units [HU]) per plaque) and volumes on non-contrast CCT were measured. A Density-Volume Calcium score was calculated by multiplying the plaque volume by a factor based on the mean HU of the plaque (4, 3, 2 and 1 for 130–199, 200–299, 300–399, and ≥400HU). Total Density-Volume Calcium score was determined by the sum of these individual scores. The semi-quantitative partially calcified and total plaque scores (PCPS and TPS) on CCTA were calculated. The associations between Density-Volume Calcium score, PCPS and TPS were examined. Results Overall, 2879 CAC plaques were assessed. Multivariable linear regression models demonstrated a stronger association between the log Density-Volume Calcium score and both the PCPS (β 0.99, 95%CI 0.80–1.19) and TPS (β 2.15, 95%CI 1.88–2.42) compared to the log of AS (PCPS: β 0.77, 95%CI 0.61–0.94; TPS: β 1.70, 95%CI 1.48–1.94). Similar results were observed for numbers of PC or TP segments. Conclusion The new CAC score weighted towards lower density demonstrated improved correlation with semi-quantitative PC and TP burden on CCTA compared to the traditional AS, which suggests it has utility as an alternative measure of atherosclerotic burden.

Objectives Elite controllers (ECs), viraemic controllers (VCs), and long-term nonprogressors (LTNPs) control HIV viral replication or maintain CD4 T-cell counts without antiretroviral therapy, but may have increased cardiovascular disease (CVD) risk compared to HIV-uninfected persons. We evaluated subclinical carotid and coronary atherosclerosis and inflammatory biomarker levels among HIV controllers, LTNPs and noncontrollers and HIV-uninfected individuals in the Multicenter AIDS Cohort Study (MACS) and the Women's Interagency HIV Study (WIHS). Methods We measured carotid plaque presence and common carotid artery intima-media thickness (IMT) in 1729 women and 1308 men, and the presence of coronary artery calcium and plaque in a subgroup of men. Associations between HIV control category and carotid and coronary plaque prevalences were assessed by multivariable regression analyses adjusting for demographics and CVD risk factors. Serum inflammatory biomarker concentrations [soluble CD163 (sCD163), soluble CD14 (sCD14), galectin-3 (Gal-3), galectin-3 binding protein (Gal-3BP) and interleukin (IL)-6] were measured and associations with HIV control category assessed. Results We included 135 HIV controllers (30 ECs) and 135 LTNPs in the study. Carotid plaque prevalence and carotid IMT were similar in HIV controllers, LTNPs and HIV-uninfected individuals. HIV controllers and LTNPs had lower prevalences of carotid plaque compared to viraemic HIV-infected individuals. The prevalence of coronary atherosclerosis was similar in HIV controllers/LTNPs compared to HIV-uninfected and viraemic HIV-infected men. Controllers and LTNPs had higher concentrations of sCD163 and sCD14 compared to HIV-uninfected persons. Conclusions Subclinical CVD was similar in HIV controllers, LTNPs and HIV-uninfected individuals despite elevated levels of some inflammatory biomarkers. Future studies of HIV controllers and LTNPs are needed to characterize the risk of CVD among HIV-infected persons.

Rationale and Objective: Glomerular filtration rate (GFR) estimation based on creatinine and cystatin C (eGFRcr-cys) is more accurate than estimated GFR (eGFR) based on creatinine or cystatin C alone (eGFRcr or eGFRcys, respectively), but the inclusion of creatinine in eGFRcr-cys requires specification of a person's race. beta 2-Microglobulin (B2M) and beta-trace protein (BTP) are alternative filtration markers that appear to be less influenced by race than creatinine is.Study Design: Study of diagnostic test accuracy.Setting and Participants: Development in a pooled population of 7 studies with 5,017 participants with and without chronic kidney disease. External validation in a pooled population of 7 other studies with 2,245 participants. Tests Compared: Panel eGFR using B2M and BTP in addition to cystatin C (3-marker panel) or creatinine and cystatin C (4-marker panel) with and without age and sex or race. Outcomes: GFRmeasured as the urinary clearance of iothalamate, plasmaclearanceof iohexol, orplasma clearance of [Cr-51]EDTA.Results: Mean measured GFRs were 58.1 and 83.2 mL/min/1.73 m(2), and the proportions of Black participants were 38.6% and 24.0%, in the development and validation populations, respectively. In development, addition of age and sex improved the performance of all equations compared with equations without age and sex, but addition of race did not further improve the performance. In validation, the 4-marker panels were more accurate than the 3-marker panels (P < 0.001). The 3-marker panel without race was more accurate than eGFRcys (percentage of estimates greater than 30% different from measured GFR [1-P30] of 15.6% vs 17.4%; P = 0.01), and the 4-marker panel without race was as accurate as eGFRcr-cys (1-P-30 of 8.6% vs 9.4%; P = 0.2). Results were generally consistent across subgroups.Limitations: No representation of participants with severe comorbid illness and from geographic areas outside of North America and Europe.Conclusions: The 4-marker panel eGFR is as accurate as eGFRcr-cys without requiring specification of race. A more accurate race-free eGFR could be an important advance.

Chronic inflammation, including among people with HIV (PWH), elevates immune cell expression of lymphocyte activation gene 3 (LAG3); however, low plasma LAG3 predicts cardiovascular disease (CVD) events in the general population. The associations among LAG3 plasma levels, subclinical atherosclerosis, inflammation, and HIV infection have not been well described. We measured plasma LAG3 in 704 men with and without HIV from the multicenter AIDS cohort study, who underwent coronary computed tomography angiography. HIV serostatus was not independently associated with LAG3 after adjustment for sociodemographic and CVD risk factors. Current smoking status and African American race were associated with lower LAG3, and age and sTNFαRI concentration were associated with greater LAG3. LAG3 was not associated with coronary artery stenosis. Thus, no difference was found in plasma LAG3 concentration by HIV serostatus, and no association between LAG3 and subclinical coronary atherosclerosis in men with and without HIV was observed.

ObjectiveWhether HIV modifies the relationship of serum lipids with coronary atherosclerosis and coronary plaque subtypes is uncertain. We examined the associations between traditional lipids and coronary atherosclerosis among HIV-infected (HIV+) and HIV-uninfected (HIV-) men.DesignThe Multicenter AIDS Cohort Study is an observational cohort with a total of 429 HIV+ and 303 HIV- men who had non-contrast cardiac computed tomography performed to measure coronary artery calcium and coronary computed tomography angiography to measure coronary stenosis, coronary plaque presence, and composition.MethodsWe used multivariable adjusted prevalence ratios to examine the relationship between the SD difference in each lipid parameter and coronary atherosclerosis.ResultsTotal cholesterol (TC)/HDL-cholesterol had the strongest associations with coronary atherosclerosis regardless of HIV status. Overall, lipid parameters were most strongly associated with the presence of mixed plaque, stenosis more than 50%, and coronary artery calcium for both HIV+ and HIV- men. HIV+ men had similar, but weaker associations, between lipid parameters and coronary atherosclerosis compared with HIV- men. The strongest association was between the TC/HDL-cholesterol and stenosis more than 50% for both HIV+ [prevalence ratios 1.25 per SD (95% confidence interval 1.07-1.43)] and HIV- men [prevalence ratios 1.46 per SD (95% confidence interval 1.08-1.85)].ConclusionThe associations between lipids and coronary atherosclerosis tended to be weaker for HIV+ compared with HIV- men, although TC/HDL had the strongest association for both HIV+ and HIV- men. A weaker association between lipid levels and coronary atherosclerosis for HIV+ men may contribute to the decreased discrimination of cardiovascular disease risk observed in HIV+ individuals.

Background High-sensitivity cardiac troponin (hs-cTn) elevations are associated with incident cardiovascular disease events in primary prevention samples. However, the mechanisms underlying this association remain unclear. Methods We studied 458 men without known cardiovascular disease who participated in the cardiovascular disease substudy of the Multicenter AIDS Cohort Study and had cardiac CT angiography. We used multivariable linear and logistic regression models to examine the cross-sectional associations between coronary artery stenosis, coronary artery plaque, indexed left ventricular mass (LVMi), and the outcome of hs-cTnI. We also evaluated the associations between HIV serostatus or use of highly active antiretroviral therapy (HAART) and hs-cTnI. Results The mean age was 54 years, 54% were white, and 61% were HIV infected. In multivariable-adjusted logistic models, comparing the highest quartile of LVMi with the lowest quartile, the odds ratio (OR) of hs-cTnI ≥75th percentile was 2.59 (95% CI, 1.20-5.75). There was no significant association between coronary stenosis severity or plaque type and hs-cTnI in linear models; however, in logistic regression models, coronary artery stenosis ≥70% (8% of sample) was marginally associated with a higher likelihood (OR, 2.75 [95% CI, 1.03, 7.27]) of having hs-cTnI ≥75th percentile. There were no associations between HIV serostatus or HAART use and hs-cTnI in either linear or logistic models. Conclusion Among primary prevention men with or at risk for HIV, hs-cTnI concentrations were strongly associated with LVMi but were not associated with HIV infection or treatment status or with coronary plaque type or stenosis until the extremes of severity (≥70% stenosis).

OBJECTIVES: Urinary biomarkers of kidney injury may have potential to identify subclinical injury attributable to tenofovir disoproxil fumarate (TDF) toxicity. DESIGN: This observational study included 198 HIV-infected participants from the Multicenter AIDS Cohort Study and the Women’s Interagency HIV Study, who initiated TDF between 2009 and 2015 and had urine samples collected at baseline before and after TDF initiation. METHODS: We used linear mixed effects models controlling for urine creatinine and time on TDF to evaluate the effects of TDF initiation on changes in fourteen urinary biomarkers. RESULTS: Within 1 year after TDF initiation, concentrations of trefoil factor 3 (+78%; 95% CI: +38%, +129%), alpha-1 microglobulin (α1m) (+32%; 95% CI: +13%, 55%), clusterin (+21%; 95% CI: +6%, +38%), uromodulin (+19%; 95% CI: +4, +36%), and kidney injury molecule-1 (KIM-1) (+13%; 95% CI: +1%, +26%) significantly increased, whereas interleukin-18 (IL-18) significantly decreased (−13%, 95% CI: −7%, −25%). Subsequent to the first year of TDF use, biomarker concentrations stabilized, and these changes were not statistically significant. When stratifying by baseline viremia (HIV-1 RNA < vs. ≥ 80 copies/mL), concentration changes for most biomarkers during the first year of TDF use were greater among aviremic versus viremic participants, with significant differences in α1m (+80% vs. +22%), KIM-1 (+43% vs. +10%), beta-2 microglobulin (+83% vs. −10%), YKL-40 (+33% vs. −5%), and IL-18 (+20% vs. −27%). CONCLUSIONS: TDF initiation was associated with substantial changes in urinary biomarkers of kidney injury within the first year of use, particularly among aviremic participants. A urinary biomarker panel may be a clinically useful tool to detect and monitor the heterogeneous effects of TDF on the kidney.

Background: HIV-infected (HIV+) persons are at increased risk of chronic kidney disease, but serum creatinine does not detect early losses in kidney function. We hypothesized that urine biomarkers of kidney damage would be associated with subsequent changes in kidney function in a contemporary cohort of HIV+ and HIV-uninfected (HIV–) men. Methods: In the Multicenter AIDS Cohort Study, we measured baseline urine concentrations of 5 biomarkers from 2009 to 2011 in 860 HIV+ and 337 HIV– men: albumin, alpha-1-microglobulin (α1m), interleukin-18 (IL-18), kidney injury molecule-1 (KIM-1), and procollagen type III N-terminal propeptide (PIIINP). We evaluated associations of urine biomarker concentrations with annual changes in estimated glomerular filtration rate (eGFR) using multivariable linear mixed models adjusted for demographics, traditional kidney disease risk factors, HIV-related risk factors, and baseline eGFR. Results: Over a median follow-up of 4.8 years, the average annual eGFR decline was 1.42 mL/min/1.73 m2/year in HIV+ men and 1.22 mL/min/1.73 m2/year in HIV– men. Among HIV+ men, the highest vs. lowest tertiles of albumin (–1.78 mL/min/1.73 m2/year, 95% CI –3.47 to –0.09) and α1m (–2.43 mL/min/1.73 m2/year, 95% CI –4.14 to –0.73) were each associated with faster annual eGFR declines after multivariable adjustment. Among HIV– men, the highest vs. lowest tertile of α1m (–2.49 mL/min/1.73 m2/year, 95% CI –4.48 to –0.50) was independently associated with faster annual eGFR decline. Urine IL-18, KIM-1, and PIIINP showed no independent associations with eGFR decline, regardless of HIV serostatus. Conclusions: Among HIV+ men, higher urine albumin and α1m are associated with subsequent declines in kidney function, independent of eGFR.

The inflammatory context of HIV infection has been posited to contribute to the higher comorbidity risk noted in HIV-infected populations. One possible pathway may involve 1,25-dihydroxyvitamin D [1,25(OH)(2)D], which plays a wide biologic role in many tissues. We sought to investigate whether inflammation was associated with vitamin D metabolites in a cohort of HIV-infected (HIV+) men receiving treatment and HIV-uninfected (HIV−) men. Vitamin D metabolites, including 25-hydroxyvitamin D [25(OH)D] and 1,25(OH)(2)D, were measured along with 24 inflammatory markers among Multicenter AIDS Cohort Study participants. Exploratory factor analysis reduced inflammatory marker data to a smaller set of inflammatory processes (IPs). Multivariate linear regression was used to evaluate associations between vitamin D metabolites and IPs. There were 466 HIV+ and 100 HIV− men, who contributed 658 stored samples from 1998 to 2008. We found three IPs with IP 1 characterized by sTNF-R2, sIL-2Rα, sCD27, BAFF, sgp130, sCD14, CXCL10 (IP-10), and sIL-6R. While none of the three IPs was associated with 25(OH)D levels in either HIV+ or HIV−, higher levels of IP 1 were significantly associated with the reduced levels of 1,25(OH)(2)D in HIV+, and a similar although nonsignificant trend was seen in HIV−. The association between 1,25(OH)(2)D and inflammation found among HIV-infected men suggests a possible mechanism whereby inflammation leads to the increased comorbidity risk noted among HIV-infected individuals.

Men with acute hepatitis B virus (HBV) infection in the Multicenter AIDS Cohort Study from 1985 to 2013 had serological testing to determine proportions with HBV recovery or chronic hepatitis B (CHB). A similar proportion of men without human immunodeficiency virus (HIV) and men with HIV receiving HBV-active antiretroviral therapy (ART) developed CHB [8.2%, 95% confidence interval (CI) 3.8-15.0% vs. 7.7%, 95% CI 2.00-36.0%]. In contrast, 17.5% (95% CI 8.7-29.9%) of men living with HIV, not on HBV-active ART developed CHB. HBV-active ART protects against developing CHB.

OBJECTIVES People living with HIV (PLWH) have increased risk of chronic disease and poor mental health. We aimed to explore HIV disease indicators, comorbidity, and risk behavior of recent antiretroviral therapy (ART) initiators to inform current needs of PLWH. METHODS Men who have sex with men (MSM) in the Multicenter AIDS Cohort Study (MACS) who initiated ART between 2010 and 2018 (recent initiators) were compared with age-, race- and geographic location-matched men who initiated ART during 2000-2009 (early initiators). Measures of HIV disease, behavior, comorbidity and mental health were collected prospectively every 6 months using standardized forms. RESULTS Recent initiators had higher current CD4 (median CD4 451 vs. 307 cells/μL, P

BACKGROUND AND OBJECTIVES: Tenofovir disoproxil fumarate (tenofovir) is associated with elevated concentrations of biomarkers of kidney damage and dysfunction in individuals with HIV. The relationship of these kidney biomarkers with longitudinal kidney function decline is unknown. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We evaluated associations of 14 urinary biomarkers of kidney injury with changes in eGFR among 198 men and women with HIV who initiated tenofovir between 2009 and 2015 in the Multicenter AIDS Cohort Study and Women’s Interagency HIV Study. Urinary biomarkers included albumin-to-creatinine ratio, α-1-microglobulin, β-2-microglobulin, cystatin C, kidney injury molecule-1 (KIM-1), IL-18, neutrophil gelatinase–associated lipocalin (NGAL), clusterin, osteopontin, uromodulin, monocyte chemoattractant protein-1, EGF, trefoil factor 3, and chitinase 3-like protein 1. We used multivariable linear mixed-effect models controlling for demographics, traditional kidney disease risk factors, and HIV-related risk factors to evaluate associations of baseline biomarkers with first-year changes in eGFR, and associations of year 1 and first-year change in biomarkers with changes in eGFR from year 1 to year 3. We used the least absolute shrinkage and selection operator method to identify a parsimonious set of biomarkers jointly associated with changes in eGFR. RESULTS: Median eGFR before tenofovir initiation was 103 (interquartile range, 88–116) ml/min per 1.73 m(2). During the first year of tenofovir use, eGFR decreased on average by 9.2 (95% confidence interval, 6.5 to 11.9) ml/min per 1.73 m(2) and was stable afterward (decrease of 0.62; 95% confidence interval, −0.85 to 2.1 ml/min per 1.73 m(2) per year). After multivariable adjustment, higher baseline β-2-microglobulin, KIM-1, and clusterin were associated with larger first-year eGFR declines, whereas higher baseline uromodulin was associated with a smaller eGFR decline. First-year increase in urinary cystatin C and higher year 1 IL-18 were associated with larger annual eGFR declines from year 1 to year 3. The parsimonious models identified higher pre-tenofovir clusterin and KIM-1, lower pre-tenofovir uromodulin, and higher year 1 IL-18 as jointly associated with larger eGFR declines. CONCLUSIONS: Urinary biomarkers of kidney injury measured before and after tenofovir initiation are associated with subsequent changes in eGFR in individuals with HIV. PODCAST: This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2018_08_28_CJASNPodcast_18_9_S.mp3

Background and aimThe association of HIV with coronary atherosclerosis has been established; however, the progression of coronary atherosclerosis over time among participants with HIV is not well known. The Multicenter AIDS Cohort Study Quantitative Coronary Plaque Progression Study is a large prospective multicenter study quantifying progression of coronary plaque assessed by serial coronary computed tomography angiography (CTA).Patients and methodsHIV-infected and uninfected men who were enrolled in the Multicenter AIDS Cohort Study Cardiovascular Substudy were eligible to complete a follow-up contrast coronary CTA 3-6 years after baseline. We measured coronary plaque volume and characteristics (calcified and noncalcified plaque including fibrous, fibrous-fatty, and low attenuation) and vulnerable plaque among HIV-infected and uninfected men using semiautomated plaque software to investigate the progression of coronary atherosclerosis over time.ConclusionWe describe a novel, large prospective multicenter study investigating incidence, transition of characteristics, and progression in coronary atherosclerosis quantitatively assessed by serial coronary CTAs among HIV-infected and uninfected men.

Atrial fibrillation (AF) leads to increased risk for stroke. Human immunodeficiency virus (HIV) is associated with cardiovascular disease (CVD), although it is unclear if HIV is associated with AF. The purpose of this study was to evaluate the association between HIV serostatus and the prevalence of AF in the Multicenter AIDS Cohort Study. A cross sectional study was conducted among 1674 HIV-infected (HIV+) and uninfected (HIV–) men who completed resting 12-lead electrocardiograms, and/or ambulatory electrocardiogram monitoring. Multivariable logistic regression was used to evaluate the association between AF, defined as the presence of either AF or atrial flutter, and HIV+ serostatus. Associations were adjusted for demographic variables, and then also for CVD risk factors. HIV+ men were younger than HIV– men (median 55.5 vs 61.7 years, P

Decreased kidney function and greater albuminuria are associated with increased incidence and extent of coronary artery calcium (CAC). We investigated whether the associations between kidney function and urine protein-to-creatinine ratio (UPCR) with CAC differ by HIV serostatus.Using data from the Multicenter AIDS Cohort Study, a prospective multicenter US study of men who have sex with men, we carried out a cross-sectional study comprised of 592 HIV-infected (HIV+) and 378 uninfected (HIV-) men who underwent noncontrast computed tomography to measure CAC. Logistic and linear regression models were used to determine whether HIV infection modified associations of estimated glomerular filtration rate and UPCR with the presence and extent of CAC, adjusting for age, race, and cardiovascular risk factors.Every 10 U decrease in estimated glomerular filtration rate below 90 ml/min/1.73 m was significantly associated with 1.3-fold [95% confidence interval (CI): 1.06-1.51] higher odds of CAC presence and was similar by HIV serostatus (Pinteraction=0.37). Greater UPCR was associated with more extensive CAC, with a change in log CAC score of 0.32 (95% CI: 0.10-0.55) per 1% increase in UPCR. There was a strong trend for effect modification by HIV serostatus for this association [HIV-: 0.75 (95% CI: 0.26-1.25); HIV+: 0.22 (95% CI: -0.03 to 0.47), Pinteraction=0.06].Greater CAC burden is apparent among individuals with early kidney disease, irrespective of HIV serostatus. Increased UPCR is associated with a greater extent of CAC with a trend for differences by HIV serostatus; a clearer proteinuria/CAC extent relationship was apparent among HIV- patients.

Background Nonalcoholic fatty liver disease (NAFLD) is a leading cause of liver disease worldwide. Elevated sex hormone-binding globulin (SHBG) levels have been observed in the setting of HIV and may protect against some metabolic disorders. We aimed to investigate whether higher SHBG levels may protect against NAFLD in men with/without HIV. Methods NAFLD was assessed using non-contrast CT in 530 men in the Multicenter AIDS Cohort Study (MACS) who drank Results Median SHBG was highest among HIV+/NAFLD- men and lowest among HIV-/NAFLD+ men. Adjusted for demographics, HIV, visceral adiposity, HOMA-IR, TT, and PNPLA3 genotype, higher SHBG was associated with lower odds of NAFLD [odds ratio(OR) 0.52 per doubling,95% confidence interval(CI) 0.34-0.80]. In separate multivariable models without SHBG, HIV (OR 0.46,95%CI 0.26-0.79) and higher adiponectin (OR 0.66 per doubling,95%CI 0.49-0.89) were associated with lower NAFLD odds, whereas TT was not significantly associated (OR 0.74 per doubling,95%CI 0.53-1.04). Adjusting for SHBG attenuated the associations of HIV (OR 0.61,95%CI 0.34-1.08) and adiponectin (OR 0.74,95%CI 0.54-1.02) with NAFLD. Conclusions SHBG levels were higher among HIV+ men, independently associated with lower NAFLD, and could partially explain the associations of HIV and higher adiponectin with lower NAFLD in our cohort. These findings suggest that SHBG may protect against NAFLD, supporting further prospective and mechanistic studies.

In HIV-infected men, both untreated and on antiretroviral therapy, and in HIV-uninfected men, greater interleukin-6 (IL-6), D-dimer, and intercellular adhesion molecule-1 (ICAM-1) levels are associated with lower small HDL particle number (HDL-P), and greater IL-6 and ICAM-1 levels are associated with lower total HDL-P., Objective Low HDL cholesterol (HDL-C) is common in people living with HIV infection, which is associated with inflammation, and correlates with greater cardiovascular disease (CVD) risk. Particles of HDL are HDL subfractions, and in some general population studies, higher small HDL particle number (HDL-P) has been associated with lower CVD risk. The objective of this study was to determine whether HIV serostatus and systemic inflammation were associated with small HDL-P in the Multicenter AIDS Cohort Study (MACS). Method The MACS is composed of HIV-infected and HIV-uninfected men. Separate linear regression analyses were conducted to evaluate the associations between outcomes (small HDL-P, large HDL-P, total HDL-P, and HDL size) and variables of interest (interleukin-6 [IL-6], D-dimer, and intercellular adhesion molecule-1 [ICAM-1] levels), with adjustment for other CVD risk factors. Results The study population included 553 HIV-infected (88.1% on current ART) and 319 HIV-uninfected men. The mean age was 52.7 years for HIV-infected men and 55.3 years for HIV-uninfected men. In separate models of the study population, higher log IL-6 was associated with lower total and small HDL-P (P < .01 for both), independent of HIV serostatus and CVD risk factors. Similar results were seen with ICAM-1. Positive HIV serostatus was associated with lower small and total HDL-P, adjusted for inflammatory markers. Conclusions Greater systemic inflammation and HIV infection both were associated with lower atheroprotective small HDL-P. This may be a potential mechanism contributing to increased cardiovascular risk among HIV-infected people.

Rationale: Impaired lung function is a potent independent predictor of coronary artery disease (CAD) in individuals without human immunodeficiency virus (HIV) infection; however, the relationship between lung function and CAD in HIV remains undefined. Objectives: To examine the relationship between lung function, CAD, mortality, and circulating biomarkers in HIV. Methods: Spirometry, diffusing capacity of the lung for carbon monoxide (Dl(CO)), emphysema, coronary artery calcium, mortality, cause of death, and biomarkers were examined in HIV-infected and uninfected individuals enrolled in a cohort study at the University of Pittsburgh. Results were then validated in the Multicenter AIDS Cohort Study (MACS) cohort. Results: We examined data on 234 participants in the Pittsburgh cohort. The mean ± standard deviation age was 49.5 ± 10.2 years old, 82.1% were male, and 67.5% were ever smokers. Among the 177 of 234 individuals with HIV infection, lower Dl(CO) (not forced expiratory volume in 1 second or emphysema) was independently associated with greater coronary artery calcium (odds ratio, 1.43 per 10% lower Dl(CO); 95% confidence interval, 1.14–1.81). HIV-infected individuals with both reduced Dl(CO) and coronary artery calcium had a much higher mortality than those with either low Dl(CO) or coronary calcium alone or with neither condition. Endothelin-1, a circulating biomarker of endothelial dysfunction, was associated with both lower Dl(CO) and greater coronary artery calcium in those with HIV infection. Results were reproducible in 144 individuals enrolled in the MACS cohort; intercellular adhesion molecule 1 was the biomarker of endothelial dysfunction assessed in the MACS cohort. Conclusions: Impaired Dl(CO) and CAD were associated with each other and with higher mortality in individuals with HIV infection.

Objective We evaluated trends and population effectiveness (tolerability, HIV suppression) of current combination antiretroviral therapy (cART) regimens mindful of treatment guidelines. Method Trend analyses included 18 017 person-visits (1457 men) on cART during 2008–2017 in the Multicenter AIDS Cohort Study. Effectiveness analyses of current regimens used 3598 person-visit–pairs (745 men) on cART in 2014–2017. Inverse-probability-of-treatment-and-censoring weighted Poisson regression with robust variances was used to evaluate the association between regimens and switching, adherence and HIV RNA, Consistent with guidelines, most recent cART initiators started with INSTI-cART, which was associated with less switching. Factors beyond those studied here, such as need for salvage therapy, unique personal characteristics, drug interactions, and cost may influence treatment decisions.

OBJECTIVES HIV infection is associated with increased prevalence of subclinical coronary plaque. The extent to which such plaque reflects effects of HIV infection or effects of long-term antiretroviral therapy (ART) use remains unclear and was the goal of this analysis. DESIGN AND METHODS We compared the prevalence and extent of coronary plaque and stenosis between users of specific ART drugs or drug classes using coronary computed tomography (CT) among HIV-infected men in the Multicenter AIDS Cohort Study. To account for time-dependent confounders, including cardiovascular disease risk factors and time-varying reasons for using specific treatments, we conducted fully adjusted logistic and linear models with inverse probability of treatment weighting. RESULTS There were 618 men who underwent noncontrast coronary CT; 450 also underwent coronary CT angiography. At the time of scanning, 81% had undetectable plasma HIV RNA. In fully adjusted models, cumulative use of zidovudine, abacavir, darunavir, and protease inhibitors as a drug class were inconsistently associated with specific forms of plaque presence or extent. CONCLUSION Among virally suppressed HIV-infected men with extensive ART exposure, no consistent associations between use of specific ART drugs and both subclinical coronary plaque presence and extent were apparent. Our findings support the hypothesis that, among virally suppressed persons, type of ART used is not in general a major determinant of subclinical coronary plaque risk.

Objective To study cardiovascular disease risk score utility, we compared the association between Framingham Risk Score (FRS)/pooled cohort equation (PCE) categories and coronary artery plaque presence by HIV serostatus and evaluated whether D : A : D risk category more accurately identifies plaque in HIV-infected men. Design Cross-sectional analysis within a substudy of the Multicenter AIDS Cohort Study. Methods Cardiac computed tomography was performed to assess coronary plaque. We evaluated the association of plaque with increasing cardiovascular disease risk score category, stratified by HIV serostatus, using logistic regression. Receiver operating characteristic curves compared the discrimination of the scores for plaque by HIV serostatus. The sensitivity and specificity of the risk scores were compared in HIV-infected men. Results The risk score category - plaque associations were stronger among HIV-uninfected men than HIV-infected men, except for noncalcified plaque. For example, the odds of coronary artery calcium more than 0 were 7.03 (95% confidence interval 4.21, 11.76) times greater among men in the PCE high-risk versus low-risk category among HIV-uninfected men, compared with just 3.13 (95% confidence interval 2.13, 4.61) times greater among men in the high-risk versus low-risk category among HIV-infected men. Among HIV-infected men, high-risk category by PCE identified the greatest percentage of men with plaque/stenosis, but with lower specificity than D : A : D and FRS. The prevalence of coronary artery calcium more than 0 among men in the PCE low-risk category was 26.5% (HIV-uninfected men) and 36.0% (HIV-infected men). Conclusions FRS and PCE categories associate with plaque burden better in HIV-uninfected men. No risk score delivered both high sensitivity and specificity among HIV-infected men.

Recent evidence has shown a complex relationship between the gut microbiota, dietary nutrients, and cardiovascular disease (CVD). Trimethylamine-N-oxide (TMAO) production, initiated by the microbiota, has been associated with CVD events. We sought to test if this association exists in HIV-infected persons. After adjusting for aspirin use and CVD risk factors, HIV-infected men were more likely to have coronary stenosis in the second and third TMAO quartiles compared with the first quartile, but did not differ significantly in the fourth quartile. We found an inverted U-shaped association between TMAO levels and the presence of coronary artery stenosis among HIV-infected men.

ContextAbnormalities in the osteoprotegerin (OPG)/receptor activator of nuclear factor-κB ligand (RANKL) axis have been observed in HIV-infected persons and have been implicated in cardiovascular disease (CVD) pathogenesis in the general population.ObjectiveTo determine associations of serum OPG and RANKL concentrations with HIV infection and subclinical atherosclerosis.DesignCross-sectional study nested within the Multicenter AIDS Cohort Study.SettingFour US academic medical centers.ParticipantsThere were 578 HIV-infected and 344 HIV-uninfected men.Main outcome measuresCoronary artery calcium (CAC) was measured by noncontrast cardiac computed tomography, and coronary stenosis and plaque characteristics (composition, presence, and extent) were measured by coronary computed tomography angiography. All statistical models were adjusted for traditional CVD risk factors.ResultsOPG concentrations were higher, and RANKL concentrations were lower among HIV-infected men compared with HIV-uninfected men (P < 0.0001 each). Among HIV-infected men, higher OPG concentrations were associated with the presence of CAC, mixed plaque, and coronary stenosis >50%, but not with plaque extent. In contrast, among HIV-uninfected men, higher OPG concentrations were associated with the extent of both CAC and calcified plaque, but not with their presence. RANKL concentrations were not associated with plaque presence or the extent among HIV-infected men, but among HIV-uninfected men, lower RANKL concentrations were associated with greater extent of CAC and total plaque.ConclusionsOPG and RANKL are dysregulated in HIV-infected men, and their relationship to the presence and extent of subclinical atherosclerosis varies by HIV status. The role of these biomarkers in CVD pathogenesis and risk prediction may be different in HIV-infected men.

The utility of longitudinal AST-to-platelet ratio index (APRI), a surrogate for hepatic fibrosis, is unknown. We compared APRI up to 9 years before liver-related death among 57 cases of viral hepatitis-infected men (91% HIV+) to matched controls. APRI was stable among controls but, among cases, increased 4.6%/year from 9 to 3 years predeath (P = 0.10) and 30%/year during the 3 years predeath (P

Objective Among people with HIV, there are few long-term studies of noninvasive ultrasound-based measurements of the carotid artery predicting major health events. We hypothesized that such measurements are associated with 10-year mortality in the Women's Interagency HIV Study (WIHS) and Multicenter AIDS Cohort Study (MACS), and that associations differ by HIV serostatus. Design Nested cohort study. Methods Participants without coronary heart disease underwent B-mode carotid artery ultrasound, with measurement of common carotid artery intima-media thickness (IMT); carotid artery plaque (focal IMT > 1.5 mm) at six locations; and Young's modulus of elasticity, a measure of arterial stiffness. We examined all-cause mortality using Cox models, controlling for demographic, behavioral, cardiometabolic, and HIV-related factors. Results Among 1722 women (median age 40 years, 90% nonwhite, 71% HIV-positive) and 1304 men (median age 50, 39% nonwhite, 62% HIV-positive), 11% died during follow-up. Mortality was higher among HIV-positive women [19.9 deaths/1000 person-years, 95% confidence interval (CI) 14.7-28.8] than HIV-positive men (15.1/1000, 95% CI 8.3-26.8). In adjusted analyses, plaque was associated with mortality (hazard ratio 1.44, 95% CI 1.10-1.88) regardless of HIV serostatus, and varied by sex (among women, hazard ratio 1.06, 95% CI 0.74-1.52; among men; hazard ratio 2.19, 95% CI 1.41-3.43). The association of plaque with mortality was more pronounced among HIV-negative (hazard ratio 3.87, 95% 1.95-7.66) than HIV-positive participants (hazard ratio 1.35, 95% CI 1.00-1.84). Arterial stiffness was also associated with mortality (hazard ratio 1.43 for highest versus lowest quartile, 95% CI 1.02-2.01). Greater common carotid artery-IMT was not associated with mortality. Conclusion Carotid artery plaque was predictive of mortality, with differences observed by sex and HIV serostatus.

OBJECTIVE: Despite effective antiretroviral therapy (HAART) and durable viral suppression, many HIV-infected individuals still do not achieve CD4+ cell count (CD4) normalization. Vitamin D has immunoregulatory functions, including inducing the development of T cells, and higher levels may improve CD4 rebound. DESIGN: Longitudinal study of men from the Multicenter AIDS Cohort Study who virally suppressed following HAART initiation and had pre- and post-HAART 25[OH]D and 1,25[OH](2)D measurements and repeated measures of CD4. METHODS: CD4 rebound was modelled using a nonlinear mixed effects model. We estimated the adjusted effect (adjusted for pre-HAART antiretroviral exposure, black race, age and CD4 at HAART initiation) of pre- and post-HAART vitamin D metabolite levels on the rate of CD4 increase and final CD4 plateau. RESULTS: Among the 263 HIV-infected HAART initiators with pre-HAART vitamin D measurements, a 1-standard deviation (SD) higher pre-HAART 25(OH) (2)D level was associated with a 9% faster rate of rise (p= 0.02) but no gain in final CD4 plateau. In contrast, a 1 SD higher 1,25(OH)(2)D level was associated with a 43-cell lower final CD4 (p=0.04). Among 560 men with post-HAART measurements, findings were similar to those for pre-HAART 25(OH) (2)D with 1 SD higher level associated with faster rate of rise but no improvement in final CD4. CONCLUSION: We found no evidence that higher vitamin D metabolite levels pre- or post-HAART are associated with better CD4 outcomes among HIV-infected HAART initiators. However, the value of pre-HAART 1,25(OH)(2)D levels as an indicator of immune response dysregulation could be further explored.

Objective Positive remodeling (PR), a coronary artery characteristic associated with risk for myocardial infarction (MI), may be more prevalent in HIV-infected (HIV+) people. We evaluated the prevalence of PR using coronary CT angiography (CCTA) in HIV+ and HIV-uninfected (HIV−) men.

Vitamin D may play an important role in a range of disease processes. In the general population, lower vitamin D levels have been associated with kidney dysfunction. HIV-infected populations have a higher risk of chronic kidney disease. Few studies have examined the link between lower vitamin D levels and kidney function decline among HIV-infected persons. We investigated the associations of serum 25-hydroxyvitamin D [25(OH)D] and 1,25-dihydroxyvitamin D [1,25(OH)2D] with kidney function decline in a cohort of HIV-infected white and black men under highly active antiretroviral therapy treatment in the vitamin D ancillary study of the Multicenter AIDS Cohort Study. The associations of 25(OH)D and 1,25(OH)2D with annual change in estimated glomerular filtration rate (eGFR) were evaluated using linear mixed effects models. This study included 187 whites and 86 blacks with vitamin D measures and eGFR ≥60 ml/min/1.73 m2 at baseline. Over a median follow-up of 8.0 years, lower 25(OH)D levels were significantly associated with faster eGFR decline in whites (adjusted annual change in eGFR, tertile 1: -2.06 ml/min/1.73 m2 vs. tertile 3: -1.23 ml/min/1.73 m2, p trend .03), while no significant association was detected in blacks. Lower 1,25(OH)2D was associated with faster kidney function decline in both whites and blacks, although the estimates were not statistically significant. In conclusion, lower 25(OH)D levels were significantly associated with faster eGFR decline in a cohort of HIV-infected white men, but not in those with black ancestry. Further research is warranted to investigate the association of 25(OH)D and 1,25(OH)2D with kidney function decline in larger and ethnically diverse populations.

Author(s): Tibuakuu, Martin; Zhao, Di; Saxena, Ankita; Brown, Todd T; Jacobson, Lisa P; Palella, Frank J; Witt, Mallory D; Koletar, Susan L; Margolick, Joseph B; Guallar, Eliseo; Korada, Sai Krishna C; Budoff, Matthew J; Post, Wendy S; Michos, Erin D | Abstract: BACKGROUND:HIV-infected individuals are at increased risk for both sarcopenia and cardiovascular disease. Whether an association between low muscle mass and subclinical coronary artery disease (CAD) exists, and if it is modified by HIV serostatus, are unknown. METHODS:We performed cross-sectional analysis of 513 male MACS participants (72% HIV-infected) who underwent mid-thigh computed tomography (CT) and non-contrast cardiac CT for coronary artery calcium (CAC) during 2010-2013. Of these, 379 also underwent coronary CT angiography for non-calcified coronary plaque (NCP) and obstructive coronary stenosis ≥50%. Multivariable-adjusted Poisson regression was used to estimate prevalence risk ratios of associations between low muscle mass (l20th percentile of the HIV-uninfected individuals in the sample) and CAC, NCP and obstructive stenosis. RESULTS:The prevalence of low thigh muscle mass was similar by HIV serostatus (20%). There was no association of low muscle mass with CAC or NCP. However, low thigh muscle mass was significantly associated with a 2.5-fold higher prevalence of obstructive coronary stenosis, after adjustment for demographics and traditional CAD risk factors [PR 2.46 (95% CI 1.51, 4.01)]. This association remained significant after adjustment for adiposity, inflammation, and physical activity. There was no significant interaction by HIV serostatus (p-interaction = 0.90). CONCLUSIONS:In this exploratory analysis, low thigh muscle mass was significantly associated with subclinical obstructive coronary stenosis. Additional studies involving larger sample sizes and prospective analyses are needed to confirm the potential utility of measuring mid-thigh muscle mass for identifying individuals at increased risk for obstructive CAD who might benefit from more aggressive risk factor management.

We evaluated associations of serum 25-hydroxyvitamin D (25[OH]D) and 1,25-dihydroxyvitamin D (1,25[OH]2D) levels in a cohort of HIV-infected and HIV-uninfected men at risk for infection in the United States. Stored samples collected between 1999 and 2008 were tested for vitamin D metabolites between 2014 and 2015. Vitamin D deficiency was defined as a serum concentration of 25[OH]D

Background Chronic kidney disease (CKD) is common among HIV-infected individuals but serum creatinine is insensitive for detecting kidney damage at early stages. We hypothesized that HIV infection would be associated with elevations in subclinical markers of kidney injury and fibrosis in a contemporary cohort of men. Methods In this cross-sectional study, we measured urine levels of interleukin-18 (IL-18), kidney injury molecule-1 (KIM-1), pro-collagen type III N-terminal pro-peptide (PIIINP) and albumin-creatinine ratio (ACR) in 813 HIV-infected and 331 uninfected men enrolled in the Multi-center AIDS Cohort Study. Results Median eGFR was 95 ml/min/1.73 m2 among African-Americans ( n=376) and 87 ml/min/1.73 m2 among Caucasians ( n=768). Among HIV-infected men, the median CD4 lymphocyte count was 572 cells/mm3 and 76% of men had undetectable HIV RNA levels. After multivariable adjustment for traditional CKD risk factors including eGFR, HIV infection was associated with 52% higher urine IL-18 (95% CI, 33%, 73%), 44% higher KIM-1 (27%, 64%), 30% higher PIIINP (15%, 47%) and 84% higher ACR (54%, 120%), with similar effect sizes among African-Americans and Caucasians ( P>0.2 for tests of interaction by race). These associations remained statistically significant in analyses that excluded persons with detectable HIV RNA levels and in models that adjusted for cumulative exposure to tenofovir disoproxil fumarate. Conclusions Compared with uninfected men, HIV-infected men had more extensive glomerular and tubulointerstitial damage, as assessed by urine biomarkers. Future studies should evaluate whether combinations of biomarkers can be used to monitor stages of kidney injury and to predict CKD risk in HIV-infected individuals.

Background We aimed to determine the relationship of circulating adipokines and inflammatory biomarkers with fatty liver among men in the Multicenter AIDS Cohort Study. Methods Noncontrast computed tomography was used to assess fatty liver and measure abdominal visceral adipose tissue (VAT) area in 526 participants without history of cardiovascular disease, heavy alcohol use, or viral hepatitis infection. Multivariable logistic regression was used to assess associations of circulating biomarker levels with fatty liver. Results Three hundred twenty-nine human immunodeficiency virus (HIV)-infected men had higher levels of several inflammatory biomarkers compared with 197 HIV-uninfected men. Among HIV-uninfected men, increased adiponectin was associated with lower odds of fatty liver (odds ratio [OR] = 0.51 per doubling, P = .02), whereas higher odds of fatty liver was observed with increased levels of the proinflammatory markers intercellular adhesion molecule (ICAM)-1 (OR = 5.30, P = .004), C-reactive protein (OR = 1.66, P = .002), interleukin (IL)-6 (OR = 1.67, P = .03), and tumor necrosis factor α receptor 2 (OR = 6.55, P = .003). Among HIV-infected men, ICAM-1 was the only proinflammatory marker associated with greater odds of fatty liver (OR = 2.67, P = .02), whereas higher adiponectin (OR = 0.57, P = .003), and osteoprotegerin levels (OR = 0.48, P = .03) were associated with lower odds. These associations were all independent of VAT. Conclusions Fatty liver is associated with a heightened inflammatory state independent of visceral adiposity in HIV-uninfected men but not in HIV-infected men. However, a heightened anti-inflammatory state may protect against fatty liver regardless of HIV serostatus.

© 2017 Chandra et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Rationale Individuals with HIV are at increased risk for coronary artery disease (CAD). Early detection of subclinical CAD by assessment of coronary artery calcium (CAC) may help risk stratify and prevent CAD events in these individuals. However, the current standard to quantify CAC i.e. Agatston scoring requires EKG-gated cardiac CT imaging. Objective To determine if the assessment of CAC using non-EKG-gated chest CT and the Weston scoring system is a useful surrogate for Agatston scores in HIV-infected and HIV-uninfected individuals. Methods and measurements CAC was assessed by both the Weston and Agatston score in 108 men enrolled in the Multicenter AIDS Cohort Study. Results Participants were 55.2 (IQR 50.4; 59.9) years old and 62 (57.4%) were seropositive for HIV. Inter-observer agreement (rs = 0.94, ê = 90.0%, p

AIDS-related morbidity and mortality have declined with advances in the treatment of human immunodeficiency virus (HIV) infection [1], and age-related diseases, such as cardiovascular disease (CVD), have emerged as leading causes of death among HIV-infected individuals [2–4]. In addition to higher rates of acute coronary events [5–7], HIV-infected individuals have more subclinical coronary atherosclerosis and endothelial dysfunction than HIV-uninfected persons [8–10]. Systemic inflammation, including monocyte activation and migration, contributes to atherogenesis [11]. Despite different biological mechanisms of action [12–14], circulating levels of soluble CD163 (sCD163) and soluble CD14 (sCD14), monocyte activation markers, and of monocyte chemoattractant protein 1 (CCL2), a proinflammatory chemokine, are reliable markers of inflammation [15–18]. Levels of all 3 biomarkers are also elevated in HIV-infected persons [13, 19, 20]. Higher levels of sCD163 are associated with coronary atherosclerosis in HIV-uninfected individuals [21] and, in some prior studies, in HIV-infected patients [22, 23]. While some studies of HIV-infected patients have demonstrated associations between sCD14 and CCL2 and subclinical coronary and carotid atherosclerosis [13, 20], others have not [22, 24]. The role of these biomarkers in coronary atherosclerosis among HIV-infected individuals requires further clarification. The purpose of this study was to evaluate associations between serum levels of sCD163, sCD14, and CCL2 and subclinical coronary atherosclerosis among a large group of well-characterized men with and those without HIV infection and to determine whether HIV infection modifies these relationships. Subclinical coronary atherosclerosis, which is associated with an increased risk of cardiac events [25, 26], was assessed using noncontrast cardiac computed tomography (CT), to measure coronary artery calcium levels, and coronary CT angiography, to measure coronary artery stenosis and the extent and composition of coronary plaque [27–30].

Previous studies demonstrated that blacks have less coronary artery calcification (CAC) than whites. We evaluated racial differences in plaque composition and stenosis in the Multicenter AIDS Cohort Study. HIV-positive and HIV-negative men underwent noncontrast cardiac computed tomography (CT) if they were aged 40 to 70 years, weighed136 kg, and had no history of cardiac surgery or revascularization and, if eligible, coronary CT angiography (CTA). There were 1,001 men who underwent CT scans and 759 men CTA. We measured CAC on noncontrast CT and identified total plaque, noncalcified plaque, calcified plaque, mixed plaque, and coronary stenosis50% on CTA. The association of presence and extent of plaque with race was determined after adjustment for HIV serostatus, cardiovascular risk factors, and measures of socioeconomic status. The prevalences of any plaque on CTA and noncalcified plaque were not different between black and white men; however, black men had lower prevalences of CAC (prevalence ratio [PR] 0.79, p = 0.01), calcified plaque (PR 0.69, p = 0.002), and stenosis50% (PR 0.59, p = 0.009). There were no associations between black race and extent of plaque in fully adjusted models. Using log-linear regression, black race was associated with a lower extent of any plaque on CTA in HIV-positive men (estimate = -0.24, p = 0.051) but not in HIV-negative men (0.12, p = 0.50, HIV interaction p = 0.005). In conclusion, a lower prevalence of CAC in black compared with white men appears to reflect less calcification of plaque and stenosis rather than a lower overall prevalence of plaque.

Objective: Cytokines released by epicardial fat are implicated in the pathogenesis of atherosclerosis. HIV infection and antiretroviral therapy have been associated with changes in body fat distribution and coronary artery disease. We sought to determine whether HIV infection is associated with greater epicardial fat and whether epicardial fat is associated with subclinical coronary atherosclerosis. Design: We studied 579 HIV-infected and 353 HIV-uninfected men aged 40–70 years with noncontrast computed tomography to measure epicardial adipose tissue (EAT) volume and coronary artery calcium (CAC). Total plaque score (TPS) and plaque subtypes (noncalcified, calcified, and mixed) were measured by coronary computed tomography angiography in 706 men. Methods: We evaluated the association between EAT and HIV serostatus, and the association of EAT with subclinical atherosclerosis, adjusting for age, race, and serostatus and with additional cardiovascular risk factors and tested for modifying effects of HIV serostatus. Results: HIV-infected men had greater EAT than HIV-uninfected men (P ¼ 0.001). EAT was positively associated with duration of antiretroviral therapy (P ¼ 0.02), specifically azidothymidine (P < 0.05). EAT was associated with presence of any coronary artery plaque (P ¼ 0.006) and noncalcified plaque (P ¼ 0.001), adjusting for age, race, serostatus, and cardiovascular risk factors. Among men with CAC, EAT was associated with CAC extent (P ¼ 0.006). HIV serostatus did not modify associations between EAT and either CAC extent or presence of plaque. Conclusion: Greater epicardial fat volume in HIV-infected men and its association with coronary plaque and antiretroviral therapy duration suggest potential mechanisms that might lead to increased risk for cardiovascular disease in HIV. 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins AIDS 2014, 28:1635–1644