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To characterize diet quality across a global cohort of people with HIV (PWH).Cross-sectional analysis.Leveraging REPRIEVE data from baseline across five Global Burden of Disease (GBD) regions, we analyzed participant responses to the Rapid Eating Assessment for Participants questionnaire. An overall diet quality score and scores for specific diet components were generated. Higher scores indicate better diet quality.Among 7736 participants (median age 50 years, 30% women, median BMI 25.8 kg/m 2 ) overall diet quality score (max score 30) was optimal in 13% of participants and good, suboptimal or poor in 45%, 38%, and 4% of participants, respectively; saturated fat score (max score 18) was good, suboptimal, or poor in 38%, 40%, or 7% of participants, respectively. Diet quality scores differed across GBD region with the highest scores reported in the South Asia region [median 23 (21-25)] and lowest in the sub-Saharan Africa region [median 15 (12-18)]; 61% of participants in the South Asia region reported optimal diet quality compared with only 6% in the sub-Saharan Africa region. Higher atherosclerotic cardiovascular risk scores were seen with worsening diet quality.Among PWH eligible for primary CVD prevention, diet quality was suboptimal or poor for almost half of participants, and there were substantial variations in diet quality reported by GBD region.NCT02344290.

Background People with HIV (PWH) have subclinical coronary artery disease (CAD) despite low traditional atherosclerotic cardiovascular disease (ASCVD) risk scores. Coronary plaque in PWH presents as a unique phenotype, but little is known about the contributions of specific inflammatory pathways to plaque phenotypes in PWH. Methods The REPRIEVE Mechanistic Substudy enrolled PWH on ART without known cardiovascular disease. We used a targeted discovery proteomics approach to evaluate 246 unique proteins representing cardiovascular, inflammatory, and immune pathways. Proteomic signatures were determined for presence of coronary artery calcium (CAC > 0) and presence of coronary plaque. Results Data were available for 662 participants (aged 51 [SD 6] years, ASCVD risk score 4.9% [SD 3.1%]). Among 12 proteins associated with both CAC and presence of coronary plaque, independent of ASCVD risk score, the odds ratios were highest for NRP1: 5.1 (95% confidence interval [CI], 2.3–11.4) for CAC and 2.9 (95% CI, 1.4–6.1) for presence of plaque. Proteins uniquely related to presence of plaque were CST3, LTBR, MEPE, PLC, SERPINA5, and TNFSF13B; in contrast, DCN, IL-6RA, OSMR, ST2, and VCAM1 were only related to CAC. Conclusions Distinct immune and inflammatory pathways are differentially associated with subclinical CAD phenotypes among PWH. This comprehensive set of targets should be further investigated to reduce atherosclerosis and ASCVD in PWH. Clinical Trials Registration NCT02344290.

Background Inflammasome activation is increased in people with human immunodeficiency virus (PWH), but its relationship with coronary plaque is poorly understood in this setting. Methods In a large human immunodeficiency virus cardiovascular prevention cohort, relationships between caspase-1, interleukin (IL)-1β, and IL-18 and coronary plaque indices were assessed by multivariate logistic regression. Results Higher IL-18 and IL-1β were associated with Leaman score, an integrative measure of plaque burden and composition. Conclusions As Leaman score >5 is associated with cardiovascular events in the general population, future work is needed to determine how the inflammasome relates to events and whether strategies to reduce its activation affect events or plaque progression among PWH.

Background We sought to explore multinational differences in functional status by global burden of disease (GBD) regions in the REPRIEVE cohort. Methods REPRIEVE is a prospective, double-blind, randomized, placebo-controlled, multicenter, phase III primary cardiovascular prevention study of pitavastatin calcium vs placebo among people with human immunodeficiency virus (HIV, PWH) ages 40–75 on antiretroviral therapy (ART). GBD super regions were defined using World Health Organization classifications. Participants were categorized by impairment on the Duke Activity Status Instrument (DASI: none, some, moderate, severe). Logistic regression models examined risk factors and GBD regions associated with functional impairment. The association between functional impairment and cardiometabolic risk was also explored. Results Of 7736 participants, the majority were from high-income countries (n = 4065), were male (65%), and had received ART for ≥ 10 years. The median DASI score was 58.2 (interquartile range [IQR] 50.2, 58.2); 36% reported at least some impairment. In adjusted analyses, functional impairment was significantly more frequent among participants from Southeast/East Asia. Other factors associated with greater impairment included female sex, Black race, older age, current/former smoking, higher body mass index, use of ART for ≥ 10 years, and select ART regimens; differences were seen in risks across GBD regions. Functional impairment was associated with increased cardiometabolic risk. Conclusions Over 1/3 of middle-aged and older PWH in a global cohort across diverse GBD regions demonstrate functional impairments. The associations between DASI and cardiometabolic risk suggest that a measure of functional status may improve risk prediction; these longitudinal associations will be further investigated over REPRIEVE trial follow-up.

To investigate relationships between Life's Simple 7 (LS7), an assessment of cardiovascular health (CVH), and coronary plaque among people with HIV (PWH).Cross-sectional.Coronary computed tomography angiography, immune/inflammatory biomarkers, and characterization of LS7 were collected among a subset of ART-treated PWH enrolled in REPRIEVE, a primary prevention trial. Analyses adjusted for cardiovascular disease risk (ASCVD score).Median age of the 735 participants was 51(±6) years, 16% female, and median (Q1-Q3) CVD risk was 4.5% (2.6-6.9). Forty percentage had poor (≤2 ideal components), 51% had intermediate (three or four ideal components), and only 9% had ideal CVH (≥5). Coronary plaque was present in 357 (49%); 167 (23%) had ≥1 vulnerable plaque features, 293 (40%) had noncalcified plaque, and 242 (35%) had a coronary artery calcium score0. All three phenotypes were increasingly more prevalent with poorer CVH and these relationships remained after adjusting for ASCVD risk. Poor CVH was associated with higher high-sensitivity C-reactive protein, oxidized low-density cholesterol, and interleukin-6. The relationship of LS7 to plaque remained after adjusting for these biomarkers.Among PWH, poor CVH as measured by LS7 was associated with coronary plaque presence, vulnerable features, and calcification. LS7 was also associated with selected biomarkers; adjustment for these and ASCVD score reduced but did not eliminate LS7's association with plaque, suggesting the possibility of additional protective mechanisms against atherogenesis and plaque remodeling. Clinical use of LS7 and further exploration of its relationships with coronary artery disease may enhance efforts to reduce cardiovascular morbidity and mortality in PWH.NCT02344290Graphical abstract, http://links.lww.com/QAD/C694.

People with HIV (PWH) are at an increased risk of developing nonalcoholic fatty liver disease (NAFLD). Interleukin (IL)-18 is regulated by inflammasomes in response to pathogens and danger signals and has been implicated in both the pathogenesis of NAFLD and HIV disease progression. We hypothesized that increased IL-18 may be associated with NAFLD and liver injury in PWH. This was an observational study of 125 PWH and 59 individuals without HIV in the Boston area. Participants with known hepatitis B, hepatitis C, and excessive alcohol use were excluded. IL-18 was measured in serum by enzyme-linked immunosorbent assay. Liver lipid content was assessed by liver-to-spleen computed tomography (CT) attenuation ratio. Aspartate aminotransferase (AST), alanine aminotransferase (ALT), and IL-18 levels were higher in PWH than in controls. In PWH, log(10) IL-18 was associated with log(10)AST (r = 0.34, p = .0001), log(10)ALT (r = 0.33, p = .0002), log(10)HIV RNA (r = 0.29, p = .002), and inversely associated with liver-to-spleen ratio (r = −0.24, p = .02). In addition, log(10) IL-18 was associated with log(10) triglycerides (r = 0.26, p = .003), log(10) MCP-1 (monocyte chemoattractant protein-1; r = 0.33, p = .0004), log(10)caspase-1 (r = 0.35, p

REPRIEVE, the Randomized Trial to Prevent Vascular Events in HIV, is a multicenter, primary prevention trial evaluating whether a statin can prevent major cardiovascular events in people with HIV. REPRIEVE is conducted at100 clinical research sites (CRSs) globally. Detailed, comprehensive, and novel methods for evaluating and communicating CRS performance are required to ensure trial integrity and data quality. In this analysis we describe a comprehensive multidimensional methodology for evaluating CRS performance.The REPRIEVE Data Coordinating and Clinical Coordinating Centers developed a robust system for evaluation of and communication with CRSs, designed to identify potential issues and obstacles to performance, provide real-time technical support, and make recommendations for process improvements to facilitate efficient trial execution. We describe these systems and evaluate their impact on participant retention, data management, and specimen management from 2019 to 2022, corresponding to the period from end of recruitment to present. This evaluation was based on pre-defined metrics, regular reviews, and bidirectional communication.Participant retention, data management, and specimen management all remained steady over the three-year period, although metrics varied by country of enrollment. Targeted messaging relating to certain performance metrics was effective.Site performance is vital to ensure trial integrity and achievement of key trial goals. This analysis demonstrates that utilization of a comprehensive approach allows for a thorough evaluation of CRS performance, facilitates data and specimen management, and enhances participant retention. Our approach may serve as a guidepost for maximizing future large-scale clinical trials' operational success and scientific rigor.gov Identifier: NCT02344290.

Background Cytomegalovirus (CMV) infection is thought to result in increased immune activation in people with human immunodeficiency virus (HIV, PWH). Although some data have linked asymptomatic CMV infection to cardiovascular disease among PWH, it remains unknown whether CMV is associated with increased or high-risk coronary plaque. Methods The Randomized Trial to Prevent Vascular Events in HIV (REPRIEVE) enrolled PWH aged 40–75 years on stable antiretroviral therapy (ART) with low-to-moderate atherosclerotic cardiovascular disease (ASCVD) risk. Among a subset of US REPRIEVE participants, coronary plaque was assessed by coronary computed tomography angiography. Here, we assessed the relationship between CMV immunoglobulin G (IgG) titer and (1) levels of immune activation, (2) inflammatory biomarkers, and (3) coronary plaque phenotypes at study entry. Results Of 672 participants, mean age was 51 years, 83% were men, median ASCVD risk score was 4.5%, and 66% had current CD4+ T-cell count ≥500 cells/mm3. Higher CMV IgG quartile group was associated with older age and lower current and nadir CD4+ T-cell counts. CMV IgG titer was associated with specific inflammatory biomarkers (sCD163, MCP-1, interleukin [IL]-6, hsCRP) in univariate analysis, but not after controlling for HIV-specific factors. In contrast, CMV IgG titer was not associated with coronary artery disease indexes, including presence of plaque, coronary artery calcium (CAC) score >0, vulnerable plaque presence, or Leaman score >5. Conclusions No meaningful association was seen between CMV IgG titer and coronary artery disease indexes among ART-treated PWH at study enrollment. Longitudinal assessments in REPRIEVE will determine the relationship of CMV IgG titer to plaque progression and cardiovascular events. Clinical Trials Registration NCT02344290.

While people with HIV (PWH) are living longer due to advances in antiretroviral therapy, recent data have demonstrated an increased risk of cardiovascular disease (CVD) among this population. This increased risk is thought to be due to both traditional (for example, smoking, diabetes) and HIV-specific (for example, inflammation, persistent immune activation) risk factors. This review focuses on the potential for statin therapy to mitigate this increased risk.Several randomized clinical trials have demonstrated that statins, a class of lipid-lowering medications, are effective as a primary CVD prevention strategy among people without HIV. Among PWH, statins have been shown to lower cholesterol, exert immunomodulatory effects, stabilize coronary atherosclerotic plaque, and even induce plaque regression.Prevention of CVD among the aging population of people with controlled, but chronic, HIV is vital. Data exploring primary prevention in this context are thus far limited. The Randomized Trial to Prevent Vascular Events in HIV (REPRIEVE) is ongoing; this trial will inform the field by investigating the effects of pitavastatin calcium as a primary prevention strategy for major adverse cardiovascular events among PWH on antiretroviral therapy (ART) at low-to-moderate traditional CVD risk.

August Among people with HIV (PWH), sex-differences in presentations of atherosclerotic cardiovascular disease (ASCVD) may be influenced by differences in coronary plaque parameters, immune/inflammatory biomarkers, or relationships therein.REPRIEVE, a primary ASCVD prevention trial, enrolled antiretroviral therapy (ART)-treated PWH. At entry, a subset of U.S. participants underwent coronary computed tomography angiography (CTA) and immune phenotyping (N = 755 CTA; N = 725 CTA + immune). We characterized sex-differences in coronary plaque and immune/inflammatory biomarkers and compared immune-plaque relationships by sex. Unless noted otherwise, analyses adjust for ASCVD risk score.The primary analysis cohort included 631 males and 124 females. ASCVD risk was higher among males (median 4.9% vs. 2.1%), while obesity rates were higher among females (48% vs. 21%). Prevalence of any plaque and of plaque with either ≥1 visible noncalcified portion or vulnerable features (NC/V-P) was lower among females overall and controlling for relevant risk factors [RR(95% CI) for any plaque 0.67 (0.50, 0.92); RR for NC/V-P 0.71 (0.51, 1.00) (adjusted for ASCVD risk score and BMI)]. Females showed higher levels of IL-6, hs-CRP, and D-dimer and lower levels of Lp-PLA2 (P 0.001 for all). Higher levels of Lp-PLA2, MCP-1, and oxLDL were associated with higher plaque (P 0.02) and NC/V-P prevalence, with no differences by sex. Among females but not males, D-dimer was associated with higher prevalence of NC/V-P (interaction P = 0.055).Among U.S. PWH, females had a lower prevalence of plaque and NC/V-P, as well as differences in key immune/inflammatory biomarkers. Immune-plaque relationships differed by sex for D-dimer, but not other tested parameters.Conference on Retroviruses and Opportunistic Infections (CROI), 2022; International Workshop on HIV and Women (IWHW), 2022; AIDS Clinical Trials Group Network Meeting, 2022; REPIREVE State of the Science Meeting, 2022.NCT0234429 (date of initial registration: January 22, 2015).

Because persons who identify across the transgender spectrum (PATS) are a key population in human immunodeficiency virus (HIV) yet are underreported in HIV and cardiovascular research, we aimed to characterize this population within the REPRIEVE global clinical trial (n = 7770). Acceptance of gathering gender identity was high (96%). Participation by PATS was 1.7% overall, 2.4% among natal males, 0.3% among natal females, and varied across geographic regions (from 0% in sub-Saharan Africa to 2.3% in High Income Region). Thirty percent of natal male PATS identified other than transgender. Some characteristics differed by gender. Most notably, 38% of natal male PATS receiving gender-affirming treatment had waist circumference >102 cm (compared with ≤25% in other groups). Given that PATS is a key population, HIV research should routinely report trial participation and outcomes by gender in addition to natal sex, to provide the results needed to optimize medical care to PATS.

Background People with human immunodeficiency virus (PWH) face increased risks for heart failure and adverse heart failure outcomes. Myocardial steatosis predisposes to diastolic dysfunction, a heart failure precursor. We aimed to characterize myocardial steatosis and associated potential risk factors among a subset of the Randomized Trial to Prevent Vascular Events in HIV (REPRIEVE) participants. Methods Eighty-two PWH without known heart failure successfully underwent cardiovascular magnetic resonance spectroscopy, yielding data on intramyocardial triglyceride (IMTG) content (a continuous marker for myocardial steatosis extent). Logistic regression models were applied to investigate associations between select clinical characteristics and odds of increased or markedly increased IMTG content. Results Median (Q1, Q3) IMTG content was 0.59% (0.28%, 1.15%). IMTG content was increased (> 0.5%) among 52% and markedly increased (> 1.5%) among 22% of participants. Parameters associated with increased IMTG content included age (P = .013), body mass index (BMI) ≥ 25 kg/m2 (P = .055), history of intravenous drug use (IVDU) (P = .033), and nadir CD4 count Conclusions A substantial proportion of antiretroviral therapy–treated PWH exhibited myocardial steatosis. Age, BMI ≥ 25 kg/m2, low nadir CD4 count, and history of IVDU emerged as possible risk factors for myocardial steatosis in this group. Clinical Trials Registration NCT02344290; NCT03238755.

Background People with human immunodeficiency virus (PWH) are at risk for accelerated development of physical function impairment and frailty; both associated with increased risk of falls, hospitalizations, and death. Identifying factors associated with physical function impairment and frailty can help target interventions. Methods The REPRIEVE trial enrolled participants 40–75 years of age, receiving stable antiretroviral therapy with CD4+ T-cell count >100 cells/mm3, and with low to moderate cardiovascular disease risk. We conducted a cross-sectional analysis of those concurrently enrolled in the ancillary study PREPARE at enrollment. Results Among the 266 participants, the median age was 51 years; 81% were male, and 45% were black, and 28% had hypertension. Body mass index (BMI; calculated as weight in kilograms divided by height in meters squared) was 25 to Conclusions Physical function impairment was common among middle-aged PWH; greater BMI and physical inactivity are important modifiable factors that may prevent further decline in physical function with aging. Clinical Trials Registration NCT02344290.

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.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.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.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.

Background Among antiretroviral therapy (ART)–treated people with human immunodeficiency virus (PWH), persistent systemic immune activation contributes to atherogenesis atherosclerotic, cardiovascular disease (CVD) events, and mortality. Factors associated with key immune activation indices have not previously been characterized among a global primary CVD prevention cohort of PWH. Methods Leveraging baseline Randomized Trial to Prevent Vascular Events in HIV (REPRIEVE) data, we evaluated factors associated with soluble CD14 (sCD14) and oxidized low-density lipoprotein (oxLDL). Results The primary analysis cohort included 4907 participants from 5 global-burden-of-disease regions (38% female, 48% Black, median age 50 years). In fully adjusted models for sCD14, female sex and White race (among those in high-income regions) were associated with higher sCD14 levels, while higher body mass index (BMI) and current use of nucleoside reverse transcriptase inhibitor + integrase strand transfer inhibitor ART were associated with lower sCD14 levels. In fully adjusted models for oxLDL, male sex, residence in high-income regions, White race (among those in high-income regions), and higher BMI were associated with higher oxLDL levels. In a subanalysis cohort of 1396 women with HIV, increased reproductive age was associated with higher sCD14 levels but not with higher oxLDL levels. Conclusions Factors associated with sCD14 and oxLDL, 2 key indices of immune-mediated CVD risk, differ. Future studies will elucidate ways in which medications (eg, statins) and behavioral modifications influence sCD14 and oxLDL and the extent to which dampening of these markers mediates CVD-protective effects. Clinical Trials Registration NCT0234429.

People with HIV (PWH) are at increased risk of cardiovasvular disease (CVD) and sudden cardiac death. Previous work has suggested an association between HIV infection and electrocardiographic (ECG) abnormalities. There are limited data on the burden of ECG abnormalities among PWH in a multiracial, multiethnic globally representative population.One hundred twenty sites in the Randomized Trial to Prevent Vascular Events in HIV (REPRIEVE).ECG findings were grouped into clinically relevant categories using sex-specific thresholds when indicated. We used the Fisher exact tests to assess associations of demographic characteristics and ECG abnormalities. We used logistic regression model to assess associations between demographic and HIV management measures, with adjustment.We analyzed data for 7720 PWH (99% of participants) (median age 50 years, 69% male participants). There were 3346 (43%) Black or African American, 2680 (35%) White, and 1139 (15%) Asian participants. Most of the participants (97%) had viral load that was400 copies/mL orlower limits of quantification. Nearly half of the participants had at least one ECG abnormality (44%). QTc prolongation was more common among male than female participants (9% vs. 6%, P = 0.001) and nearly twice as common among Asian participants (12%) when compared with other racial groups (7%) (P0.0001). Participants with viral load400 copies/mL had approximately twice the odds of prolonged QTc compared with those that were undetectable (adjusted OR: 2.05, 95% CI: 1.22 to 3.45).Prolonged QTc is common among male, Asian, and REPRIEVE participants with higher viral loads. These relationships warrant future investigation of linkages to ensuing CVD events among PWH.

Limited data are available regarding asymptomatic COVID-19 among people with HIV (PWH). Data on a representative subset of PWH enrolled in Randomized Trial to Prevent Vascular Events in HIV, a global clinical trial, are presented here.Randomized Trial to Prevent Vascular Events in HIV is an atherosclerotic cardiovascular disease prevention trial among 7770 PWH on antiretroviral therapy. Beginning April 2020, targeted data on coronavirus disease 2019 (COVID-19) diagnosis and symptoms were collected during routine trial visits. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection was defined as either COVID-19 clinical diagnosis or presence of SARS-CoV-2 Immunoglobulin G (IgG) or Immunoglobulin A (IgA) receptor binding domain protein (antispike) antibodies in the absence of prior COVID-19 vaccine.The group (N = 2464) had a median age 53 years, 35% female sex, 47% Black or African American race, median CD4 count 649 c/mm 3 , and 97% with HIV VL400 cp/m. SARS-CoV-2 infection occurred in 318 persons (13%): 58 with clinical diagnosis and 260 with detectable antibodies. Of these PWH, 304 completed symptom questionnaires: 121 (40%) reported symptoms, but 183 (60%) were asymptomatic. PWH with asymptomatic SARS-CoV-2 infection were more likely to be from low-income or middle-income regions, of Black or African American race, older in age, and with higher atherosclerotic cardiovascular disease risk score. Symptomatic COVID was more common with obesity, metabolic syndrome, and low HDL levels. CD4 counts and HIV viral suppression rates were similar among PWH with symptomatic vs. asymptomatic COVID.Asymptomatic SARS-CoV-2 infection is common among antiretroviral therapy-treated PWH globally. We determined that 60% of infections in PWH were asymptomatic. HIV clinicians must remain vigilant about COVID-19 testing among PWH to identify asymptomatic cases.

Little is known regarding coronavirus disease 2019 (COVID-19) vaccination rates in people with HIV (PWH), a vulnerable population with significant morbidity from COVID-19. We assessed COVID-19 vaccination rates among 6952 PWH in the Randomized Trial to Prevent Vascular Events in HIV (REPRIEVE) compared to region- and country-specific vaccination data. The global probability of COVID-19 vaccination through end of July 2021 was 55% among REPRIEVE participants with rates varying substantially by Global Burden of Disease (GBD) superregion. Among PWH, factors associated with COVID-19 vaccination included residence in high-income regions, age, white race, male sex, body mass index, and higher cardiovascular risk. Clinical Trials Registration. NCT02344290.

Background In addition to traditional cardiovascular (CV) risk factors, antiretroviral therapy, lifestyle, and human immunodeficiency virus (HIV)-related factors may contribute to future CV events in persons with HIV (PWH). Methods Among participants in the global REPRIEVE randomized trial, we characterized demographics and HIV characteristics relative to ACC/AHA pooled cohort equations (PCE) for atherosclerotic CV disease predicted risk and CV health evaluated by Life’s Simple 7 (LS7; includes smoking, diet, physical activity, body mass index, blood pressure, total cholesterol, and glucose). Results Among 7382 REPRIEVE participants (31% women, 45% Black), the median PCE risk score was 4.5% (lower and upper quartiles Q1, Q3: 2.2, 7.2); 29% had a PCE score, Measures of cardiovascular (CV) risk and health are not closely related in persons with human immunodeficiency virus (HIV) in the REPRIEVE trial. Poor health scores among low-CV-risk persons with HIV suggest a critical role for lifestyle interventions regardless of CV risk prediction.

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

Background Emerging data demonstrate that the use of integrase inhibitor (INSTI)-based antiretroviral treatment (ART) is associated with increased weight, but the cardiometabolic health consequences of increased weight remains poorly understood. Methods This analysis examined INSTI use (>6 months) at entry among REPRIEVE participants enrolled in High Income and Latin America/Caribbean Global Burden of Disease regions. Primary analyses used linear and logistic regression; secondary analyses used quantile regression to examine differences across the full data distribution. Characteristics of those with and without INSTI use were balanced using inverse probability of treatment weighting. Results Among 4500 REPRIEVE participants, 1848 were on an INSTI-based regimen at entry for an average of 2.1 ± 1.8 years. Integrase inhibitor use (vs no INSTI use) was associated with higher odds of obesity (odds ratio [OR], 1.63; 95% confidence interval [CI], 1.4–1.9) and higher mean body mass index ([BMI] +1.5kg/m2; 95% CI, 1.0–1.9) and waist circumference (+3.6cm; 95% CI, 2.6–4.6). Differences in weight related to INSTI use were greater in the upper tails of the distribution (+3.1kg/m2 [95% CI, 1.9–4.4] at the 90th centile vs +0.7kg/m2 [95% CI, 0.2–1.2] at the 50th centile) and among women and nonwhite participants, with sex and race having an additive effect on BMI. Conversely, INSTI use was not associated with differences in glucose, low-density lipoprotein cholesterol, or higher odds of metabolic syndrome or hypertension. Conclusions Differences in weight and waist circumference associated with INSTI use are (1) not uniform across people with human immunodeficiency virus, (2) greatest among women and nonwhites, and (3) concentrated at the upper tails of weight distribution. These data identify at-risk subgroups for whom long-term cardiovascular disease outcomes should be carefully assessed., INSTI-based regimens are associated with higher weight but not with increased cardiovascular risk for most INSTI users. Differences in weight are not uniform across PWH, and specific subgroups of INSTI users should be monitored for long-term CVD outcomes.

Prior studies in people living with HIV (PLWH) suggest added sweetener intake exceeds recommendations and associates with cardiometabolic abnormalities. Little is known of factors that associate with increased sweetener consumption in PLWH. This cross-sectional study explored knowledge and consumption of added sweeteners and associations of social determinants of health (SDoH) among 900 PLWH residing in the United States. Demographics, SDoH, and added sweetener knowledge and consumption were assessed via an online survey, multivariable analyses were completed. Results demonstrate that sex, race, and low educational level associated with lower sweetener knowledge. Race, age, body mass index, income, limited access to fresh fruits/vegetables, and low sweetener knowledge associated with higher sweetener consumption. Findings highlight the need for consideration of specific demographics and inequitable social circumstances when developing nutrition lifestyle strategies, inclusive of added sweetener education, that are feasible and sustainable across diverse community settings of PLWH.Estudios previos en personas que viven con el VIH (PLWH) sugieren que la ingesta adicional de edulcorantes excede las recomendaciones y se asocia con anomalías cardiometabólicas. Poco se sabe de los factores que se asocian con un mayor consumo de edulcorantes en PLWH. Este estudio transversal exploró el conocimiento y el consumo de edulcorantes agregados y las asociaciones de los determinantes sociales de la salud (SDoH) entre 900 PLWH que residen en los Estado Unidos. Lo datos demográficos, SDoH, y en conocimiento y el consumo de edulcorantes añadidos se evaluaron mediante una encuesta en línea y se completaron análisis multivariables. Los resultados demuestran que el sexo, la raza y el bajo nivel educativo se asocian con un menor conocimiento sobre edulcorantes. Raza, edad, índice de masa corporal, ingresos, acceso limitado a frutas/verduras frescas y conocimiento bajo sobre edulcorantes asociado con un mayor consumo edulcorantes. Los hallazgos resaltan la necesidad de considerar la demografía específica y las circunstancias sociales desiguales al desarrollar estrategias de estilo de vida nutricional, incluida la educación adicional sobre edulcorantes, que sean factibles y sostenibles en diversos entornos comunitarios de PLWH.

Cardiovascular disease (CVD) is more frequent among people with HIV (PWH) and may relate to traditional and nontraditional factors, including inflammation and immune activation. A critical need exists to develop effective strategies to prevent CVD in this population.The Randomized Trial to Prevent Vascular Events in HIV (REPRIEVE) (A5332) is a prospective, randomized, placebo-controlled trial of a statin strategy for the primary prevention of major adverse cardiovascular events (MACE) in PWH with low to moderate traditional risk. At least 7,500 PWH, 40-75 years of age, on stable antiretroviral therapy, will be randomized to pitavastatin calcium (4 mg/d) or identical placebo and followed for up to 8 years. Participants are enrolled based on the 2013 American College of Cardiology (ACC)/American Heart Association (AHA) atherosclerotic cardiovascular disease (ASCVD) risk score and low-density lipoprotein cholesterol (LDL-C) level with a goal to identify a low- to moderate-risk population who might benefit from a pharmacologic CVD prevention strategy. Potential participants with a risk score ≤ 15% were eligible based on decreasing LDL-C thresholds for increasing risk score7.5% (LDL-C190 mg/dL for risk score7.5%, LDL-C160 mg/dL for risk score 7.6%-10%, and LDL-C130 mg/dL for risk score 10.1%-15%). The primary objective is to determine effects on a composite end point of MACE. Formal and independent adjudication of clinical events will occur using standardized criteria. Key secondary end points include effects on MACE components, all-cause mortality, specified non-CVD events, AIDS and non-AIDS events, and safety.To date, REPRIEVE has enrolled7,500 participants at approximately 120 sites across 11 countries, generating a diverse and representative population of PWH to investigate the primary objective of the trial.REPRIEVE is the first trial investigating a primary CVD prevention strategy in PWH. REPRIEVE will inform the field of the efficacy and safety of a statin strategy among HIV-infected participants on antiretroviral therapy and provide critical information on CVD mechanisms and non-CVD events in PWH.

Background People with HIV (PWH) have increased cardiovascular events, inflammation, and high-risk coronary atherosclerosis. Statin therapy has been shown to lower the risk of cardiovascular disease (CVD) in the general population, but whether this results from reductions in coronary atherosclerosis and is mediated by decreased inflammation remains unknown. Methods REPRIEVE is a randomized, placebo-controlled trial of pitavastatin calcium (4 mg/day) vs. placebo enrolling at least 7500 PWH between 40–75 years, on antiretroviral therapy (ART), with low to moderate traditional CVD risk. The Mechanistic Substudy of REPRIEVE (A5333s) is co-enrolling 800 participants from 31 US sites. These participants undergo serial contrast enhanced coronary computed tomography angiography (CCTA) and measurements of biomarkers of inflammation and immune activation at baseline and after 2 years of follow-up. The primary objectives are to determine the effects of pitavastatin on noncalcified coronary atherosclerotic plaque (NCP) volume, low attenuation plaque, and positive remodeling and on changes in immune activation and inflammation and to assess relationships between the two. Changes in CAD will be assessed in a standardized fashion by a core lab with expert readers blinded to time points and participant information; immune activation and inflammation assessment is also performed centrally. Results To date the Mechanistic Substudy has completed planned enrollment, with 805 participants. Conclusion This study represents the first large, randomized, CCTA-based assessment of the effects of a primary prevention strategy for CVD on high-risk CAD, immune activation and inflammation among PWH. The study will assess pitavastatin’s effects on coronary plaque, and the interrelationship of these changes with biomarkers of immune activation and inflammation in PWH to determine mechanisms of CVD prevention and improved outcomes in this population.

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

Food systems are at the center of a brewing storm consisting of a rapidly changing climate, rising hunger and malnutrition, and significant social inequities. At the same time, there are vast opportunities to ensure that food systems produce healthy and safe food in equitable ways that promote environmental sustainability, especially if the world can come together at the UN Food Systems Summit in late 2021 and make strong and binding commitments toward food system transformation. The NIH-funded Nutrition Obesity Research Center at Harvard and the Harvard Medical School Division of Nutrition held their 22nd annual Harvard Nutrition Obesity Symposium entitled “Global Food Systems and Sustainable Nutrition in the 21st Century” in June 2021. This article presents a synthesis of this symposium and highlights the importance of food systems to addressing the burden of malnutrition and noncommunicable diseases, climate change, and the related economic and social inequities. Transformation of food systems is possible, and the nutrition and health communities have a significant role to play in this transformative process.

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 (IL1β, 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.

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.

Background Patterns of antiretroviral therapy (ART) use and immunologic correlates vary globally, and contemporary trends are not well described. Methods The REPRIEVE trial (Randomized Trial to Prevent Vascular Events in HIV) enrolled persons with human immunodeficiency virus (HIV) who were aged 40–75 years, receiving ART, and had low-to-moderate cardiovascular disease risk. ART use was summarized within Global Burden of Disease (GBD) super-regions, with adjusted linear and logistic regression analyses examining associations with immune parameters and key demographics. Results A total of 7770 participants were enrolled, with a median age of 50 years (interquartile range, 45–55 years); 31% were female, 43% were black or African American, 15% were Asian, 56% had a body mass index >25 (calculated as weight in kilograms divided by height in meters squared), and 49% were current or former smokers. The median CD4 T-cell count was 620/µL (interquartile range, 447–826/ µ L), and the median duration of prior ART use, 9.5 years (5.3–14.8) years. The most common ART regimens were nucleoside/nucleotide reverse-transcriptase inhibitor (NRTI) plus nonnucleoside reverse-transcriptase inhibitor (43%), NRTI plus integrase strand transfer inhibitor (25%), and NRTI plus protease inhibitor (19%). Entry ART varied by GBD region, with shifts during the trial enrollment period. In adjusted analyses, entry CD4 cell count and CD4/CD8 ratio were associated with GBD region, sex, entry regimen, duration of ART, and nadir CD4 cell count; CD4 and CD8 cell counts were also associated with body mass index and smoking status. Conclusions There were substantial variations in ART use by geographic region and over time, likely reflecting the local availability of specific medications, changes in treatment guidelines and provider/patient preferences. The analyses of CD4 cell counts and CD4/CD8 ratios may provide valuable insights regarding immune correlates and outcomes in people living with HIV. Clinical Trials Registration NCT02344290.

BackgroundChronic kidney disease is a common comorbid condition among persons living with human immunodeficiency virus (PWH). We characterized baseline kidney function in the REPRIEVE (Randomized Trial to Prevent Vascular Events in HIV) trial cohort.MethodsREPRIEVE enrolled PWH with low to moderate cardiovascular risk based on traditional risk factors to evaluate the effect of statin therapy on cardiovascular events. We determined baseline estimated glomerular filtration rate (eGFR) with the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI), Modification of Diet in Renal Disease, and Cockcroft-Gault equations, and we evaluated baseline factors associated with eGFR ResultsAmong 7770 participants enrolled, the median age was 50 years, 31% were female (natal sex), 43% black or African American and 15% Asian, the median body mass index (calculated as calculated as weight in kilograms divided by height in meters squared) was 25.8, and the median CD4 cell count 620/µL. The median CKD-EPI eGFR was 97 mL/min/1.73 m2, and 38% had an eGFR ConclusionsREPRIEVE enrolled a diverse cohort including a substantial number of PWH with reduced kidney function. Factors associated with reduced eGFR included traditional risk factors and tenofovir disoproxil fumarate exposure. Three commonly used equations have only fair agreement, with potential implications for both clinical care and epidemiologic studies.Clinical Trials RegistrationNCT02344290.

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 ± 7 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 ± 0.2 vs. 0.9 ± 0.2 mg/dl, P = 0.96) and eGFR (96 ± 22 vs. 96 ± 24 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.

OBJECTIVE Persons living with HIV (PLWH) well treated on antiretroviral therapies remain at risk for ensuing arterial disease. We investigated the relationship between adipose depots and biomarkers of arterial injury and inflammation to gain insight into the link between body composition and CVD risk. DESIGNS/METHODS One hundred and fifty-five HIV-infected and 70 non-HIV infected individuals were well phenotyped for body composition. Adipose depots were assessed via single-slice abdominal computed tomography (CT). Circulating markers of arterial disease and generalized inflammation [lipoprotein-associated phospholipase A2 (LpPLA2), oxidized low-density lipoprotein (oxLDL), high-sensitivity cardiac troponin T (hs-cTnT), high-sensitivity C-reactive protein (hsCRP)] were evaluated. RESULTS Despite similar BMI and visceral adipose tissue (VAT), HIV-infected individuals had significantly lower subcutaneous adipose tissue [SAT, 199 (126-288) vs. 239 (148-358) cm(2), P = 0.04] than non-HIV infected individuals. Among HIV-infected individuals, reduced SAT inversely correlated with LpPLA2 (ρ = -0.19, P = 0.02) and hs-cTnT (ρ = -0.24, P = 0.004), whereas increased VAT significantly and positively related to LpPLA2 (ρ = 0.25, P = 0.003), oxLDL (ρ = 0.28, P = 0.0005), hs-cTnT (ρ = 0.28, P = 0.0007) and hsCRP (ρ = 0.32, P =

Objective Fatty liver disease is increased among individuals with HIV. We sought to explore how aldosterone, a key hormone linked to insulin resistance and inflammation, relates to liver fat in the large population of individuals with HIV and metabolic abnormalities. Methods Forty-six individuals with HIV and increased waist circumference and dysglycemia were assessed for liver fat using proton magnetic resonance spectroscopy. Serum aldosterone level was obtained following strictly controlled posture conditions and a standardized sodium diet and was related to liver fat. Results Among the entire group [median (interquartile range) liver fat: 5% (3%, 12%) and homeostatic model assessment of insulin resistance: 1.74 (1.21, 2.83)], serum aldosterone significantly correlated with liver fat (r = 0.31; P = 0.049). Liver fat level was significantly higher in those with aldosterone above vs below the median [8% (3%, 20%) vs 4% (2%, 10%); P = 0.02]. In the presence of metabolic syndrome, individuals with aldosterone levels above vs below the median had markedly elevated liver fat values [14% (9%, 23%) vs 5% (3%, 12%); P = 0.005] and increased presence of fatty liver disease (FLD; 92% vs 50%; P = 0.02). Controlling for metabolic syndrome, hepatitis C virus, and alcohol use, aldosterone was a significant and independent predictor of liver fat (β estimate: 0.6038, P = 0.01; overall model r2 = 0.41, P = 0.0005) and FLD (OR: 1.38, P = 0.02; overall model r2 = 0.28, P = 0.002). Conclusion These data highlight a robust association between aldosterone and liver fat among individuals with HIV and metabolic dysregulation. Increased aldosterone may be a risk factor for liver fat accumulation among the population with HIV.

Background In high-resource settings, the HIV-attributable risk of myocardial infarction (MI) is higher among women than among men. The extent to which unique mechanisms contribute to MI risk among women vs. men with HIV remains unclear. Methods Subclinical coronary atherosclerotic plaque characteristics-including high-risk morphology plaque features-were compared among 48 HIV-infected women [48 (41, 54) years] and 97 HIV-infected men [48 (42, 52) years] on stable antiretroviral therapy (ART) without known cardiovascular disease. These individuals had previously completed coronary computed tomography angiography and metabolic/immune phenotyping as part of a prospective study. Results Extending previous analyses, now focusing exclusively on ART-treated participants, we found that HIV-infected women had a lower prevalence of any subclinical coronary atherosclerotic plaque (35% vs. 62%, P = 0.003) and a lower number of segments with plaque (P = 0.01), compared with HIV-infected men. We also report for the first time that ART-treated HIV-infected women had a lower prevalence of high-risk positively remodeled plaque (25% vs. 51%, P = 0.003) and a lower number of positively remodeled plaque segments (P = 0.002). In models adjusting for cardiovascular risk factors, we further showed that male sex remained associated with any coronary plaque [odds ratio 3.8, 95% confidence interval: (1.4 to 11.4)] and with positively remodeled plaque [odds ratio 3.7, 95% confidence interval: (1.4, 10.9)]. Conclusions ART-treated HIV-infected women (vs. HIV-infected men) had a lower prevalence and burden of subclinical coronary plaque and high-risk morphology plaque. Thus, unique sex-specific mechanisms beyond subclinical plaque may drive the higher HIV-attributable risk of MI among women vs. men.

BACKGROUND: In observational studies, HIV patients have higher levels of soluble ST2 (sST2), galectin-3, growth differentiation factor-15 (GDF-15) than non-HIV controls. As statins exert pleiotropic immunomodulatory effects that may affect markers of myocardial fibrosis, the objective of the current study is to determine if biomarkers of myocardial fibrosis reflecting subclinical pathology may be modified by statin therapy in patients with HIV. SETTING AND METHODS: 40 HIV+ men and women participated in a single center 12-month randomized, double-blind placebo controlled trial of atorvastatin 40mg qd vs. placebo. At baseline and 12-months sST2, GDF-15, galectin-3, were measured. RESULTS: The changes in sST2 were −0.310 [−4.195,2.075] vs. 1.163 [0.624, 4.715]ng/mL, median[IQR] atorvastatin vs. placebo (p=0.04). The change in sST2 was significantly related to changes in monocyte activation markers sCD14 (r=0.63, p

OBJECTIVE: Monocyte/macrophage activation is increased among people with HIV, and may contribute to the heightened risk of atherosclerosis and neurocognitive dysfunction in this population. Insulin-like growth factor 1 (IGF-1) has been shown to attenuate the innate immune response in animal models of atherosclerosis and inflammatory bowel disease. We investigated for the first time relationships of circulating IGF-1 with monocyte/macrophage-specific indices among HIV-infected individuals and uninfected controls. DESIGN: Observational. METHODS: 131 HIV-infected subjects and 65 well-matched controls without known cardiac disease or viral hepatitis were recruited previously. IGF-1, expressed as a z-score relative to the age- and sex-adjusted population mean, was related to log-transformed inflammatory markers within HIV and non-HIV groups. RESULTS: In HIV, IGF-1 inversely related to sCD163 (r = −0.28, P = 0.002), sCD14 (r = −0.29, P = 0.002), and high-sensitivity IL-6 (r = −0.27, P = 0.006). There was no association of IGF-1 with high-sensitivity CRP, MCP-1, IL-18, or LPS in HIV, or between IGF-1 and any inflammatory marker in controls. Relationships of IGF-1 with sCD163 and sCD14 remained significant in HIV after controlling for age, sex, smoking, body mass index, visceral fat, statin use, viral load, and antiretroviral therapy. For every 1-unit decline in IGF-1 z-score, sCD163 and sCD14 increased by 14% (95% CI, 0.23%, 29%) and 29% (95% CI, 1.4%, 63%), respectively. CONCLUSIONS: Low IGF-1 was robustly associated with high sCD163 and sCD14 in HIV. Prospective studies are needed to investigate augmentation of IGF-1 as a novel strategy to reduce monocyte/macrophage activation in this population.

Context HIV-infected individuals demonstrate increased renin-angiotensin-aldosterone system activation in association with visceral adiposity, insulin resistance, and inflammation. A physiologically based treatment approach targeting mineralocorticoid receptor (MR) blockade may improve metabolic and inflammatory indices in HIV. Objective To investigate effects of eplerenone on insulin sensitivity, inflammatory indices, and other metabolic parameters in HIV. Design Six-month, double-blind, randomized, placebo-controlled trial. Setting Academic clinical research center. Participants HIV-infected individuals with increased waist circumference and abnormal glucose homeostasis. Intervention Eplerenone 50 mg or placebo daily. Outcome The primary end point was change in insulin sensitivity measured by the euglycemic-hyperinsulinemic clamp technique. Secondary end points included change in body composition and inflammatory markers. Results Forty-six individuals were randomized to eplerenone (n = 25) vs placebo (n = 21). Eplerenone did not improve insulin sensitivity [0.48 (-1.28 to 1.48) vs 0.43 (-1.95 to 2.55) mg/min/μIU/mL insulin; P = 0.71, eplerenone vs placebo] when measured by the gold standard euglycemic-hyperinsulinemic clamp technique. Intramyocellular lipids (P = 0.04), monocyte chemoattractant protein-1 (P = 0.04), and high-density lipoprotein (P = 0.04) improved among those randomized to eplerenone vs placebo. Trends toward decreases in interleukin-6 (P = 0.10) and high-sensitivity C-reactive protein (P = 0.10) were also seen with eplerenone vs placebo. Plasma renin activity and aldosterone levels increased in the eplerenone vs placebo-treated group, demonstrating expected physiology. MR antagonism with eplerenone was well tolerated among the HIV population, with no considerable changes in blood pressure or potassium. Conclusion MR blockade may improve selected metabolic and inflammatory indices in HIV-infected individuals. Further studies are necessary to understand the clinical potential of MR antagonism in HIV.

Background Mechanisms underlying the heightened myocardial infarction risk among HIV-infected women (versus non-HIV-infected women) remain unclear. Our objectives were to assess epicardial adipose tissue (EAT) volume and its associations among asymptomatic women with and without HIV. Methods A total of 55 HIV-infected and 27 non-HIV-infected women without known cardiovascular disease who underwent cardiac CT and metabolic/immune phenotyping were included. EAT volume derived from CT was compared among women with and without HIV, and within-group EAT associations were assessed. Next, immune and atherosclerotic plaque parameters were compared among groups stratified by HIV serostatus and high/low EAT (defined in reference to median EAT for each serostatus group). Results Asymptomatic HIV-infected women and age-matched non-HIV-infected women with comparable mean body mass index (28 ±1 versus 29 ±1 kg/m2) had similar median (IQR) volumes of EAT (54 [41–79] versus 65 [41–78] cm3; P>0.05); however, different within-group associations were noted. Markers of monocyte activation/arterial inflammation differed by HIV serostatus/EAT volume subgroup (CXCL10 [ P=0.02], sCD163 [ P=0.004], sCD14 [ P=0.03], Lp-PLA2 [ P=0.04]; P for overall ANOVA) and were highest among HIV-infected women with excess EAT (versus HIV-infected women without excess EAT, non-HIV-infected women with excess EAT and non-HIV-infected women without excess EAT). The percentage of segments with non-calcified coronary plaque also differed by HIV serostatus/EAT volume subgroup and was highest among HIV-infected women with excess EAT. Conclusions Asymptomatic women with and without HIV have similar volumes of EAT, but drivers of EAT may differ between groups. HIV-infected women with excess EAT have highest-level immune activation and the highest percentage of non-calcified plaque. Future studies are needed to determine whether EAT contributes pathogenetically to HIV-associated cardiovascular disease in women.

BackgroundWomen's under-representation in HIV and cardiovascular disease (CVD) research suggests a need for novel strategies to ensure robust representation of women in HIV-associated CVD research.ObjectiveTo elicit perspectives on CVD research participation among a community-sample of women with or at risk for HIV, and to apply acquired insights toward the development of an evidence-based campaign empowering older women with HIV to participate in a large-scale CVD prevention trial.MethodsIn a community-based setting, we surveyed 40 women with or at risk for HIV about factors which might facilitate or impede engagement in CVD research. We applied insights derived from these surveys into the development of the Follow YOUR Heart campaign, educating women about HIV-associated CVD and empowering them to learn more about a multi-site HIV-associated CVD prevention trial: REPRIEVE.ResultsEndorsed best methods for learning about a CVD research study included peer-to-peer communication (54%), provider communication (46%) and video-based communication (39%). Top endorsed non-monetary reasons for participating in research related to gaining information (63%) and helping others (47%). Top endorsed reasons for not participating related to lack of knowledge about studies (29%) and lack of request to participate (29%). Based on survey results, the REPRIEVE Follow YOUR Heart campaign was developed. Interwoven campaign components (print materials, video, web presence) offer provider-based information/knowledge, peer-to-peer communication, and empowerment to learn more. Campaign components reflect women's self-identified motivations for research participation - education and altruism.ConclusionsInvestigation of factors influencing women's participation in HIV-associated CVD research may be usefully applied to develop evidence-based strategies for enhancing women's enrollment in disease-specific large-scale trials. If proven efficacious, such strategies may enhance conduct of large-scale research studies across disciplines.

Background People with human immunodeficiency virus (PWH) demonstrate increased atherosclerotic cardiovascular disease (ASCVD). Statins are being studied to prevent ASCVD in human immunodeficiency virus (HIV), but little is known regarding the effects of statins on a broad range of inflammatory and cardiovascular proteins in this population. Methods We used a highly specific discovery proteomic approach (Protein Extension Assay), to determine statin effects on over 350 plasma proteins in relevant ASCVD pathways among HIV and non-HIV groups. Responses to pitavastatin calcium were assessed in 89 PWH in the INTREPID trial and 46 non-HIV participants with features of central adiposity and insulin resistance. History of cardiovascular disease was exclusionary for both studies. Results Among participants with HIV, PCOLCE (enzymatic cleavage of type I procollagen) significantly increased after pitavastatin therapy and PLA2G7 (systemic marker of arterial inflammation) decreased. Among participants without HIV, integrin subunit alpha M (integrin adhesive function) and defensin alpha-1 (neutrophil function) increased after pitavastatin therapy and PLA2G7 decreased. At baseline, comparing participants with and without HIV, differentially expressed proteins included proteins involved in platelet and endothelial function and immune activation. Conclusions Pitavastatin affected proteins important to platelet and endothelial function and immune activation, and effects differed to a degree within PWH and participants without HIV.

This short communication demonstrates how conducting a focus group with members of a proposed study population of interest can help inform the suitability of study interventions and appeal of recruitment strategies prior to study commencement. People living with HIV (PLWH) were recruited to participate in a focus group to elicit feedback on the content and design of an online survey on sweetener knowledge and consumption; and usability of the survey which was ultimately launched nationally. Ten participants (age 55 years, 60% male, 70% non-Caucasian, 60% income