Coronary Microvascular Dysfunction Is Present Among Well-Treated Asymptomatic Persons With HIV and Similar to Those With Diabetes.

Background: Coronary microvascular dysfunction (CMD) could be a potential underlying mechanism for myocardial disease in HIV. Methods: Comparisons of coronary flow reserve corrected for heart rate-blood pressure product (CFRCOR) were made among people with HIV (PWH) with no known history of cardiovascular disease (CVD) or diabetes mellitus, persons without HIV (PWOH), and persons with diabetes (PWDM) and no known history of CVD or HIV. Results: PWH (n = 39, 74% male, age 55 [7] years, body mass index [BMI] 32.3 (26.8-34.9) kg/m2, duration of antiretroviral therapy 13 [5] years, CD4+ count 754 [598-961] cells/µL) were similar to PWOH (n = 69, 74% male, age 55 [8] years, BMI 32.2[25.6-36.5] kg/m2) and PWDM (n = 63, 63% male, age 55 [8] years, BMI 31.5 [28.6-35.6] kg/m2). CFRCOR was different among groups: PWOH 2.76 (2.37-3.36), PWH 2.47 (1.92-2.93), and PWDM 2.31 (1.98-2.84); overall P = .003. CFRCOR was reduced comparing PWH to PWOH (P = .04) and PWDM to PWOH (P = .007) but did not differ when comparing PWH to PWDM (P = .98). A total 31% of PWH had CFRCOR < 2.0, a critical cutoff for CMD, compared to 14% of PWOH and 27% with PWDM. A total 40% of women with HIV had a CFRCOR < 2.0 compared to 6% of women without HIV (P = .02). Conclusions: Subclinical CMD is present among chronically infected and well-treated, asymptomatic PWH who are immunologically controlled. This study demonstrates CFR is reduced in PWH compared to PWOH and comparable to PWDM, further highlighting that well-treated HIV infection is a CVD-risk enhancing factor for CMD similar to diabetes. Clinical Trials Registration: NCT02740179.

Participant perspectives on management and communication of incidental findings identified on radiographic imaging performed during a clinical research trial: A single site pilot study.

Background: Incidental findings (IFs) in radiographic imaging are unexpected discoveries unrelated to the purpose of the scan. While the protocol for communicating IFs is better defined for clinical providers, little formal guidance on communicating IFs identified on research scans to participants is available. This study explored participants' experience with communication and management of IFs found on imaging identified in a clinical research trial. Methods: Participants who completed the parent clinical trial, which included imaging, were invited to participate. A survey, developed by the study team, was administered telephonically, and consisted of multiple choice and open-ended questions. Results: Thirty participants enrolled in the survey study. Ninety-three percent of all participants (with and without IFs) reported they would participate in another research study to learn information that was important to their health. Seventeen participants reported being notified about an IF on their study scan(s). Ninety-four percent of those participants with an IF were satisfied with how the IF was communicated, and 71 % were grateful to find out about a health problem before it became an issue. Forty-one percent reported that learning about the IF led to improved health. Content analysis of the data from the open-ended questions revealed categories and themes which enriched the quantitative data. Conclusion: Participants generally wanted to know when an IF was discovered unexpectedly on their imaging scan, as they learned important information about their health. Findings underscore the importance of having a clear protocol for communicating IFs to research study participants that undergo evaluation with radiographic imaging.

Mineralocorticoid Receptor Antagonism by Eplerenone and Arterial Inflammation in HIV: The MIRABELLA HIV Study.

Importance: The risk for atherosclerotic disease is increased 1.5- to 2.0-fold among persons with HIV (PWH). Increased activation of the renin-angiotensin-aldosterone system may contribute to increased arterial inflammation in this population. Objective: To determine the effects of eplerenone on arterial inflammation among well-treated PWH without known cardiovascular disease (CVD). Design, Setting, and Participants: Well-treated PWH who participated in the double-blinded, placebo-controlled, Mineralocorticoid Receptor Antagonism for Cardiovascular Health in HIV (MIRACLE HIV) study between February 2017 and March 2022 assessing the effects of eplerenone on myocardial perfusion were invited to participate in the Mineralocorticoid Receptor Antagonism By Eplerenone to Lower Arterial Inflammation in HIV (MIRABELLA) substudy if there was no current statin use. Participants were enrolled in the MIRABELLA study and underwent additional 18F-fludeoxyglucose-positron emission tomography/computed tomography (18F-FDG PET/CT) imaging of the aorta and carotid arteries to assess arterial inflammation over 12 months of treatment with eplerenone vs placebo. Interventions: Eplerenone, 50 mg, twice a day vs identical placebo. Main Outcomes and Measures: The primary outcome was change in target to background ratio (TBR), a measure of arterial wall inflammation, in the index vessel after 12 months of treatment. The index vessel was defined as the vessel (aorta, left carotid artery, or right carotid artery) with the highest TBR at baseline in each participant. Results: A total of 26 participants (mean [SD] age, 54 [7] years; 18 male [69%]) were enrolled in the study. Treatment groups (eplerenone, 13 vs placebo, 13) were of similar age, sex, and body mass index. Eplerenone was associated with a reduction in TBR of the primary end point, the index vessel (eplerenone vs placebo: model treatment effect, -0.31; 95% CI, -0.50 to -0.11; P = .006; percentage change, -12.4% [IQR, -21.9% to -2.6%] vs 5.1% [IQR, -1.6% to 11.0%]; P = .003). We further observed a significant reduction of the TBR of the most diseased segment (MDS) of the index vessel (eplerenone vs placebo: -19.1% [IQR, -27.0% to -11.9%] vs 6.8% [IQR, -9.1% to 12.1%]; P = .007). A similar result was seen assessing the index vessel of the carotids (eplerenone vs placebo: -10.0% [IQR, -21.8% to 3.6%] vs 9.7% [IQR, -9.8% to 15.9%]; P = .046). Reduction in the TBR of MDS of the index vessel on 18F-FDG PET/CT correlated with improvement in the stress myocardial blood flow on cardiac magnetic resonance imaging (Spearman ρ = -0.67; P = .01). Conclusion and Relevance: In this small randomized clinical trial, eplerenone was associated with reduction in arterial inflammation among well-treated PWH without known CVD. In addition, reductions in arterial inflammation as measured by 18F-FDG PET/CT were related to improvements in stress myocardial perfusion. Further larger studies should explore whether eplerenone is a potential treatment strategy for inflammatory-mediated CVD in PWH. Trial Registration: ClinicalTrials.gov Identifier: NCT02740179.

Large lessons learned from small vessels: coronary microvascular dysfunction in HIV.

PURPOSE OF REVIEW: Large cohort studies have consistently shown the presence of heart failure is approximately doubled among persons with HIV (PWH). Early studies of cardiovascular disease (CVD) in HIV were primarily focused on atherosclerotic burden, and we now have a greater understanding of large vessel disease in HIV. More recent studies have begun to inform us about small vessel disease, or coronary microvascular dysfunction (CMD), in HIV. CMD is recognized to be an important risk factor for adverse events related to heart failure, associated with cardiovascular mortality, and often presents without overt atherosclerotic disease. RECENT FINDINGS: In this review, we highlight implications for CMD and relevant clinical studies in HIV. Inflammation and endothelial dysfunction, well known risk factors in HIV, may mediate the pathogenesis of CMD. Initial studies suggest that CMD worsens with ART initiation. Newer studies reveal CMD is present among well treated PWH without known CVD. In addition, myocardial flow reserve (MFR), a marker of CMD, is reduced in HIV similar to diabetes. There also appears to be sex differences, such that CMD is worse among women vs. men with HIV. SUMMARY: Alterations in the coronary microvasculature may be an important mediator of subclinical myocardial dysfunction that deserves further clinical attention among PWH without known CVD.

Visceral Adiposity Index as a Measure of Cardiovascular Disease in Persons With Human Immunodeficiency Virus.

Background: Persons with well-treated human immunodeficiency virus (HIV) demonstrate a 2-fold higher risk of cardiovascular disease (CVD), which may be related to excess visceral adipose tissue (VAT). The visceral adiposity index (VAI) is a score to approximate VAT by combining biochemical measures with anthropometrics without quantification by imaging. We evaluated VAI in association with cardiometabolic factors among persons with HIV (PWH). Methods: Forty-five PWH on antiretroviral therapy and virologically controlled with increased abdominal VAT (VAT area >110 cm2 on CT) and no known CVD were included. VAI was calculated using standard sex-specific formulas. Coronary plaque was assessed using coronary CT angiography. Results: Participants were predominantly male (73%), white (53%), and non-Hispanic (84%), with a mean age of 55 (standard deviation, 7) years. Among PWH, median VAI was calculated to be 4.9 (interquartile range [IQR], 2.8-7.3). Log VAI correlated with log VAT (r = 0.59, P < .0001) and anthropometric measures (body mass index: r = 0.36, P = .02; waist circumference: r = 0.43, P = .004; waist-to-hip ratio: r = 0.33, P = .03). Participants with coronary plaque had a higher VAI compared to those without coronary plaque (median, 5.3 [IQR, 3.4-10.5] vs 2.8 [IQR, 1.8-5.0]; P = .004). VAI (area under the curve = 0.760, P = .008) performed better than the atherosclerotic CVD risk score to predict the presence of plaque in receiver operating characteristic analyses. Conclusions: VAI may be a useful biomarker of metabolic dysfunction and increased CVD risk that may occur with VAT accumulation in PWH. Clinical Trials Registration: NCT02740179.

Randomized Placebo-Controlled Trial to Evaluate Effects of Eplerenone on Myocardial Perfusion and Function Among Persons With Human Immunodeficiency Virus (HIV)-Results From the MIRACLE HIV Study.

BACKGROUND: Increased renin angiotensin aldosterone system (RAAS) activity may contribute to excess cardiovascular disease in people with HIV (PWH). We investigated how RAAS blockade may improve myocardial perfusion, injury, and function among well-treated PWH. METHODS: Forty PWH, on stable ART, without known heart disease were randomized to eplerenone 50 mg PO BID (n = 20) or identical placebo (n = 20) for 12 months. The primary endpoints were (1) myocardial perfusion assessed by coronary flow reserve (CFR) on cardiac PET or stress myocardial blood flow (sMBF) on cardiac MRI or (2) myocardial inflammation by extracellular mass index (ECMi) on cardiac MRI. RESULTS: Beneficial effects on myocardial perfusion were seen for sMBF by cardiac MRI (mean [SD]: 0.09 [0.56] vs -0.53 [0.68] mL/min/g; P = .03) but not CFR by cardiac PET (0.01 [0.64] vs -0.07 [0.48]; P = .72, eplerenone vs placebo). Eplerenone improved parameters of myocardial function on cardiac MRI including left ventricular end diastolic volume (-13 [28] vs 10 [26] mL; P = .03) and global circumferential strain (GCS; median [interquartile range 25th-75th]: -1.3% [-2.9%-1.0%] vs 2.3% [-0.4%-4.1%]; P = .03), eplerenone versus placebo respectively. On cardiac MRI, improvement in sMBF related to improvement in global circumferential strain (ρ = -0.65, P = .057) among those treated with eplerenone. Selecting for those with impaired myocardial perfusion (CFR <2.5 and/or sMBF <1.8), there was a treatment effect of eplerenone versus placebo to improve CFR (0.28 [0.27] vs -0.05 [0.36]; P = .04). Eplerenone prevented a small increase in troponin (0.00 [-0.13-0.00] vs 0.00 [0.00-0.74] ng/L; P = .03) without effects on ECMi (0.9 [-2.3-4.3] vs -0.7 [-2.2--0.1] g/m2; P = .38). CD4+ T-cell count (127 [-38-286] vs -6 [-168-53] cells/µL; P = .02) increased in the eplerenone- versus placebo-treated groups. CONCLUSIONS: RAAS blockade with eplerenone benefitted key indices and prevented worsening of myocardial perfusion, injury, and function among PWH with subclinical cardiac disease when compared with placebo. CLINICAL TRIALS REGISTRATION: NCT02740179 (https://clinicaltrials.gov/ct2/show/NCT02740179?term=NCT02740179&draw=2&rank=1).

Primary Aldosteronism and COVID-19-related Management, Disease Severity, and Outcomes: A Retrospective Cohort Study.

Context: The SARS-CoV-2 virus is dependent on components of the renin-angiotensin-aldosterone system for infectivity. Primary aldosteronism (PA) is a form of secondary hypertension mediated by autonomous aldosterone production. The intersection of COVID-19 and PA, both which may involve components of the renin-angiotensin-aldosterone system, remains unknown. Methods: We assessed PA as a risk factor for COVID-19 infection and compared management, severity of disease, and outcomes during COVID-19 with a matched population of patients with essential hypertension (EH) by conducting a retrospective observational cohort study. Results: Of the patients with PA, 81 had a negative PCR test for COVID-19, whereas 43 had a documented positive PCR test for COVID-19. Those patients with PA who tested positive for COVID-19 tended to be female (P = .08) and the majority of those with COVID-19 infection identified as non-White race (P = .02) and Hispanic ethnicity (P = .02). In a subanalysis, 24-hour urine aldosterone on initial PA diagnosis tended to be higher those in the PA group who developed COVID-19 compared with those in the PA group who did not develop COVID-19 [median (interquartile range): 36.5 (16.9, 54.3) vs 22.0 (15.8, 26.8) mcg, P = .049] and was an independent predictor of COVID-19 infection controlling for sex, race, and ethnicity. Angiotensin-converting enzyme inhibitor, angiotensin II receptor blocker, and mineralocorticoid receptor antagonist use did not differ between those patients with PA who did and did not have COVID-19 infection. Comparing those patients with PA and matched patients with EH (n = 286) who were COVID-19 PCR positive, there was a significantly higher incidence of cardiovascular complications (12 vs 2%, P = .004) in the PA vs EH group. Conclusion: These data begin to inform us as to whether PA should be a newly identified subpopulation at risk for COVID-19-related cardiovascular disease sequelae.

Do patients with larger body sizes undergo more CT exams?

BACKGROUND: Overweight and obese patients are known to have more diseases than normal weight individuals, but it is currently unknown if there is higher utilization of computed tomography (CT) exams among those with larger body sizes. AIMS: To examine whether patients with larger body sizes undergo more CT exams and by how much more. METHODS: Using the recently described T-shirt size assessed from the lateral and transverse dimensions in CT localizer radiographs as a surrogate for body size, patients were classified into seven T-shirt sizes (XXS, XS, S, M, L, XL, XXL). This multi-center study analyzed over one million CT exams performed in 256 medical institutions in the USA to assess the frequency of CT use in patients of different body sizes. RESULTS: It was found that patients with larger body sizes (L, XL, XXL sizes) underwent 2.5-3.5 times more CT scans in the chest region and 7.8-17.7 times in the abdominopelvic region as compared to those with smaller body sizes (XXS, XS, S sizes). Further, the patients with extra-large body sizes (XL and XXL) underwent 4.6-9.9 times scans in the chest region and 39.2-187.8 times scans in the abdominopelvic region as compared to those with extra-small body sizes (XXS and XS). CONCLUSIONS: Our first-of-its-kind study demonstrating the manyfold use of CT in patients with large body sizes may be interesting for healthcare policy planning and developing guidelines for allocating resources for obese patients.

Accounting for radiation exposure from previous CT exams while deciding on the next exam: What do referring clinicians think?

PURPOSE: To obtain clinicians' views of the need to account for radiation exposure from previous CT scans and the advisability of a regulatory mechanism to control the number of CT scans for an individual patient. METHODS: A convenience survey was conducted by emailing a link to a three-question electronic survey to clinicians in many countries, mostly through radiology and radiation protection contacts. RESULTS: 505 responses were received from 24 countries. 293 respondents (58%) understand that current regulations do not limit the number of CT scans that can be prescribed for a single patient in a year. When asked whether there should be a regulation to limit the number of CT scans that can be prescribed for a single patient in one year, only a small fraction (143, 28%) answered 'No', 182 (36%) answered 'Maybe' and 166 (33%) answered 'Yes'. Most respondents (337; 67%) think that radiation risk should form part of the consideration when deciding whether to request a CT exam. A minority (138; 27%) think the decision should be based only on the medical indication for the CT exam. Comparison among the 4 countries (South Korea, Hungary, USA and Canada) with the largest number of respondents indicated wide variations in responses. CONCLUSIONS: A majority of the surveyed clinicians consider radiation risk, in addition to clinical factors, when prescribing CT exams. Most respondents are in favor of, or would consider, regulation to control the number of CT scans that could be performed on a patient annually.

Role of renin-angiotensin-aldosterone system activation and other metabolic variables in relation to arterial inflammation in HIV.

BACKGROUND: Arterial inflammation remains increased among persons with HIV (PWH) compared with persons without HIV (PWOH) even when controlling for traditional risk factors. We sought to understand whether increased renin-angiotensin-aldosterone system (RAAS) activation may be related to arterial inflammation in PWH and when compared with PWOH. DESIGN: Twenty PWH and 9 PWOH followed a controlled, standardized low and liberal sodium diet to simulate a RAAS-activated and RAAS-suppressed state, respectively. We measured serum lipoprotein-associated phospholipase A2 (LpPLA2) concentrations following both conditions to assess the physiologic dynamics of aldosterone in relation to arterial inflammation. RESULTS: LpPLA2 levels were significantly higher among PWH versus PWOH during both the RAAS-activated state[5.3(4.2, 6.1) versus 4.0(3.0, 4.8)nmol/L, median(interquartile range),p = .01]) and RAAS-suppressed state[4.4(3.9, 5.3) versus 3.8(3.4, 4.1)nmol/L,p = .01]. Among PWH, but not PWOH, LpPLA2 increased significantly with RAAS activation(p = .03). LpPLA2 levels measured during the RAAS-suppressed state among PWH remained relatively higher than LpPLA2 levels under both conditions among PWOH. Log LpPLA2 was related to log aldosterone during the RAAS-activated state(r = .39,p = .04) among all participants. Log LpPLA2 was correlated with visceral fat(r = .46,p = .04) and log systolic blood pressure(r = .57,p = .009) during a RAAS-activated state when an increase in aldosterone was stimulated in HIV. CONCLUSION: LpPLA2 is increased during a RAAS-activated state among PWH, but not among PWOH. Further, LpPLA2 was increased in both RAAS-activated and suppressed states in PWH compared with PWOH. These data suggest a biological link between increased aldosterone and arterial inflammation in this population. Future studies should test RAAS blockade on arterial inflammation as a targeted treatment approach in HIV.

Evaluation of Mineralocorticoid Receptor Antagonism on Changes in NT-proBNP Among Persons With HIV.

Subclinical myocardial dysfunction is prevalent among well-treated persons with HIV (PWH). We have previously demonstrated unique renin-angiotensin-aldosterone system physiology among PWH with metabolic dysregulation. Mineralocorticoid receptor blockade may be a targeted treatment strategy for subclinical heart disease in PWH. Forty-six PWH were randomized to receive either eplerenone 50 mg daily or placebo in a 6-month randomized, double-blinded, placebo-controlled trial. We assessed changes in N-terminal pro-B-type natriuretic peptide (NT-proBNP), a biomarker of cardiac stretch, under controlled posture and dietary conditions. The eplerenone- and placebo-treated groups demonstrated a long duration of HIV with good immunological control. NT-proBNP levels were similar between the groups at baseline (41.1 [20.2, 97.9] vs 48.9 [29.2, 65.4] ng/L, P = .80) and decreased significantly more in the eplerenone- vs placebo-treated groups after 6 months (change NT-proBNP -9.6 [-46.8, 0.3] vs -3.0 [-17.0, 39.9] ng/L, P = .02 for comparison of change between groups). Decreases in NT-proBNP were independent of changes in systolic and diastolic blood pressure, and related to decreases in high-sensitivity C-reactive protein (ρ = 0.32, P = .05) and inversely to increases in serum aldosterone (ρ = -0.33, P = .04) among all participants. Treatment with eplerenone for 6 months vs placebo significantly decreases NT-proBNP levels among PWH, independent of eplerenone's known blood pressure-lowering effects. Further studies should elucidate whether lowering NT-proBNP in this at-risk metabolic population with subclinical heart disease will offer cardioprotection. CLINICAL TRIAL REGISTRATION: NCT01405456.

Altered pattern of circulating miRNAs in HIV lipodystrophy perturbs key adipose differentiation and inflammation pathways.

We identified a microRNA (miRNA) profile characterizing HIV lipodystrophy and explored the downstream mechanistic implications with respect to adipocyte biology and the associated clinical phenotype. miRNA profiles were extracted from small extracellular vesicles (sEVs) of HIV-infected individuals with and without lipodystrophic changes and individuals without HIV, among whom we previously showed significant reductions in adipose Dicer expression related to HIV. miR-20a-3p was increased and miR-324-5p and miR-186 were reduced in sEVs from HIV lipodystrophic individuals. Changes in these miRNAs correlated with adipose Dicer expression and clinical markers of lipodystrophy, including fat redistribution, insulin resistance, and hypertriglyceridemia. Human preadipocytes transfected with mimic miR-20a-3p, anti-miR-324-5p, or anti-miR-186 induced consistent changes in latent transforming growth factor beta binding protein 2 (Ltbp2), Wisp2, and Nebl expression. Knockdown of Ltbp2 downregulated markers of adipocyte differentiation (Fabp4, Pparγ, C/ebpa, Fasn, adiponectin, Glut4, CD36), and Lamin C, and increased expression of genes involved in inflammation (IL1ß, IL6, and Ccl20). Our studies suggest a likely unique sEV miRNA signature related to dysregulation of Dicer in adipose tissue in HIV. Enhanced miR-20a-3p or depletion of miR-186 and miR-324-5p may downregulate Ltbp2 in HIV, leading to dysregulation in adipose differentiation and inflammation, which could contribute to acquired HIV lipodystrophy and associated metabolic and inflammatory perturbations.

Coronary Vasculature and Myocardial Structure in HIV: Physiologic Insights From the Renin-Angiotensin-Aldosterone System.

The landscape of HIV medicine dramatically changed with the advent of contemporary antiretroviral therapies, which has allowed persons with HIV (PWH) to achieve good virologic control, essentially eliminating HIV-related complications and increasing life expectancy. As PWH are living longer, noncommunicable diseases, such as cardiovascular disease (CVD), have become a leading cause of morbidity and mortality in PWH with rates that are 50% to 100% higher than in well-matched persons without HIV. In this review, we focus on disease of the coronary microvasculature and myocardium in HIV. We highlight a key hormonal system important to cardiovascular endocrinology, the renin-angiotensin-aldosterone system (RAAS), as a potential mediator of inflammatory driven-vascular and myocardial injury and consider RAAS blockade as a physiologically targeted strategy to reduce CVD in HIV.

Relationship of Telomere Length to Fat Redistribution in HIV.

Persons with HIV demonstrate increased risk for aging-associated complications and have reduced telomere length (TL) compared with age-matched persons without HIV. Our data show that greater visceral fat is related to reduced TL in HIV, independent of age and smoking. Fat redistribution may be a relevant mediator of TL attrition in HIV.

Measures of Adipose Tissue Redistribution and Atherosclerotic Coronary Plaque in HIV.

OBJECTIVE: People with HIV (PWH) who are well treated on antiretroviral therapy remain at increased risk for body composition changes, including increased visceral adipose tissue (VAT) and reduced subcutaneous adipose tissue (SAT), as well as increased cardiovascular disease (CVD). The relationship between adipose compartments and coronary disease is not well understood among PWH. METHODS: A total of 148 PWH and 68 uninfected individuals without CVD were well phenotyped for VAT and SAT via single-section abdominal computed tomography (CT) at L4. Coronary artery calcium (CAC) score was assessed by noncontrast cardiac CT and coronary plaque composition by coronary CT angiography. RESULTS: Increased VAT was significantly related to increased presence of plaque (OR, 1.55 per 100 cm2 ; P = 0.008) and CAC > 0 (OR, 1.56 per 100 cm2 ; P = 0.006) in the HIV group. In contrast, increased SAT was related to reduced presence of plaque (OR, 0.79 per 100 cm2 ; P = 0.057) and reduced CAC > 0 (OR, 0.69 per 100 cm2 , P = 0.007) among PWH. The VAT to SAT ratio showed a strong relationship to overall presence of calcified plaque (OR, 3.30; P = 0.03) and CAC > 0 (OR, 3.57; P < 0.001) in the HIV group. VAT and waist to hip ratio, but not SAT, were strong predictors of plaque in the uninfected group. BMI did not relate in either group. CONCLUSIONS: Fat redistribution phenotyping by simultaneous quantification of VAT and SAT as independent measures could help identify those PWH at higher risk for CVD.

Brief Report: Adipogenic Expression of Brown Fat Genes in HIV and HIV-Related Parameters.

CONTEXT: Persons with HIV are at increased risk for adipose dysfunction, which could mediate metabolic complications such as cardiovascular disease, fatty liver disease, and diabetes. We have previously reported reduced browning and beiging capacity of the subcutaneous adipose depot in HIV. OBJECTIVE: We sought to evaluate how HIV-related parameters are related to the expression of brown and beige fat genes in the abdominal subcutaneous adipose tissue. DESIGN: Eighteen persons with HIV underwent punch biopsy of abdominal subcutaneous fat to determine mRNA expression of adipose-related genes using quantitative reverse transcriptase-polymerase chain reaction. RESULTS: Duration of antiretroviral therapy use, particularly related to protease inhibitor use, was significantly related to reduced expression of multiple brown and beige fat genes (including UCP1, PGC1α, PRDM16 and others, all P ≤ 0.04) in the abdominal subcutaneous fat. In addition, duration of HIV and CD4 T-cell count were significantly correlated with reduced expression of multiple brown and beige fat genes in the abdominal subcutaneous fat (PGC1α, P2XR5, TMEM26, CD137, all P ≤ 0.05 for duration of HIV; and PGC1α, ZIC1, PRDM16, PAT2, P2RX5, TMEM26, CD137, all P ≤ 0.04). In contrast, HIV viral load did not correlate with any brown or beige fat genes. CONCLUSIONS: Key HIV-related parameters reflective of nonacute infection (increased duration of HIV and duration of antiretroviral therapy use) or relatively reduced immunologic function (lower CD4 count) were linked to reduced expression of brown and beige fat gene in the abdominal subcutaneous adipose depot. CLINICAL TRIAL REGISTRATION: NCT01098045.