Search

Background People with human immunodeficiency virus (HIV) have been reported to have increased risk of clinical and subclinical cardiovascular disease. Existing studies have focused on men and often have been uncontrolled or lacked adequate HIV-negative comparators. Methods We performed echocardiography in the Women's Interagency HIV Study to investigate associations of HIV and HIV-specific factors with cardiac phenotypes, including left ventricular systolic dysfunction (LVSD), isolated LV diastolic dysfunction (LVDD), left atrial enlargement (LAE), LV hypertrophy (LVH), and increased tricuspid regurgitation velocity (TRV). Results Of 1654 participants (age 51 ± 9 years), 70% had HIV. Sixty-three (5.4%) women with HIV (WWH) had LVSD; 71 (6.5%) had isolated LVDD. Compared with women without HIV (WWOH), WWH had a near-significantly increased risk of LVSD (adjusted relative risk = 1.69; 95% confidence interval = 1.00 to 2.86; P = .051). No significant association was noted for HIV seropositivity with other phenotypes, but there was a risk gradient for decreasing CD4+ count among WWH that approached or reached significance for isolated LVDD, LAE, and LVH. WWH with CD4+ count Conclusions This study suggests that WWH have a higher risk of LVSD compared with sociodemographically similar WWOH, but their risk for isolated LVDD, LAE, LVH, and high TRV is increased only with reduced CD4+ count. Although these findings warrant replication, they support the importance of cardiovascular risk-factor and HIV-disease control for heart disease prevention in this population.

Background: Alterations in gut microbiota and blood metabolomic profiles have been implicated in HIV infection and cardiovascular disease. However, it remains unclear whether alterations in gut microbiota may contribute to disrupted host blood metabolomic profiles in relation to atherosclerosis, especially in the context of HIV infection. Methods: We analyzed cross-sectional associations between gut microbiota features and carotid artery plaque in 361 women with or at high risk of HIV (67% HIV+), and further integrated plaque-associated microbial features with plasma lipidomic/metabolomic profiles. Furthermore, in 737 women and men, we examined prospective associations of baseline gut bacteria-associated lipidomic and metabolomic profiles with incident carotid artery plaque over 7-year follow-up. Results: We found 2 potentially pathogenic bacteria, Fusobacterium and Proteus , were associated with carotid artery plaque; while the beneficial butyrate producer Odoribacter was inversely associated with plaque. Fusobacterium and Proteus were associated with multiple lipids/metabolites which were clustered into 8 modules in network. A module comprised of 9 lysophosphatidylcholines and lysophosphatidylethanolamines and a module comprised of 9 diglycerides were associated with increased risk of carotid artery plaque (risk ratio [95% CI], 1.34 [1.09–1.64] and 1.24 [1.02–1.51] per SD increment, respectively). Functional analyses identified bacterial enzymes in lipid metabolism associated with these plasma lipids. In particular, phospholipase A1 and A2 are the key enzymes in the reactions producing lysophosphatidylcholines and lysophosphatidylethanolamines. Conclusions: Among individuals with or at high risk of HIV infection, we identified altered gut microbiota and related functional capacities in the lipid metabolism associated with disrupted plasma lipidomic profiles and carotid artery atherosclerosis.

Immune dysfunction and chronic inflammation are characteristic of HIV infection and diabetes mellitus, with CD4 + T-cell metabolism implicated in the pathogenesis of each disease. However, there is limited information on CD4 + T-cell metabolism in HIV+ persons with diabetes mellitus. We examined CD4 + T-cell glucose metabolism in HIV+ women with and without diabetes mellitus.A case-control study was used to compare CD4 + T-cell glucose metabolism in women with HIV with or without diabetes mellitus.Nondiabetic (HIV+DM-, N = 20) or type 2 diabetic HIV+ women with (HIV+DM+, N = 16) or without (HIV+DMTx+, N = 18) antidiabetic treatment were identified from the WIHS and matched for age, race/ethnicity, smoking status and CD4 + cell count. CD4 + T-cell immunometabolism was examined by flow cytometry, microfluidic qRT-PCR of metabolic genes, and Seahorse extracellular flux analysis of stimulated CD4 + T cells.HIV+DM+ displayed a significantly elevated proportion of CD4 + T cells expressing the immunometabolic marker GLUT1 compared with HIV+DMTx+ and HIV+DM- ( P = 0.04 and P = 0.01, respectively). Relative expression of genes encoding key enzymes for glucose metabolism pathways were elevated in CD4 + T cells of HIV+DM+ compared with HIV+DMTx+ and HIV+DM-. T-cell receptor (TCR)-activated CD4 + T cells from HIV+DM+ showed elevated glycolysis and oxidative phosphorylation compared with HIV+DM-.CD4 + T cells from HIV+DM+ have elevated glucose metabolism. Treatment of diabetes mellitus among women with HIV may partially correct CD4 + T-cell metabolic dysfunction.

HIV status may influence survival from non-small cell lung cancer (NSCLC). Among NSCLC patients in the Bronx, NY, we assessed (1) associations of CD4 count, CD4/CD8 ratio and HIV viral load (VL) with survival and (2) prognostic factors among persons living with HIV (PLWH). We compared survival from NSCLC diagnosis (2004-2017) between HIV-negative persons (HIV-, n=2,881) and PLWH (n=88) accounting for clinical and sociodemographic factors. HIV-survival was also compared with PLWH, dichotomized by CD4 (

Describe engagement in HIV care over time after initial engagement in HIV care, by gender identity.Observational, clinical cohort study of people with HIV engaged in routine HIV care across the United States.We followed people with HIV who linked to and engaged in clinical care (attending ≥2 visits in 12 months) in cohorts in the North American Transgender Cohort Collaboration, 2000-2018. Within strata of gender identity, we estimated the 7-year (84-month) restricted mean time spent: lost-to-clinic (stratified by pre/postantiretroviral therapy (ART) initiation); in care prior to ART initiation; on ART but not virally suppressed; virally suppressed (≤200 copies/ml); or dead (pre/post-ART initiation).Transgender women ( N = 482/101 841) spent an average of 35.5 out of 84 months virally suppressed (this was 30.5 months for cisgender women and 34.4 months for cisgender men). After adjustment for age, race, ethnicity, history of injection drug use, cohort, and calendar year, transgender women were significantly less likely to die than cisgender people. Cisgender women spent more time in care not yet on ART, and less time on ART and virally suppressed, but were less likely to die compared with cisgender men. Other differences were not clinically meaningful.In this sample, transgender women and cisgender people spent similar amounts of time in care and virally suppressed. Additional efforts to improve retention in care and viral suppression are needed for all people with HIV, regardless of gender identity.

Atherosclerosis is accompanied by a CD4 T cell response to apolipoprotein B (APOB). Major Histocompatibility Complex (MHC)-II tetramers can be used to isolate antigen-specific CD4 T cells by flow sorting. Here, we produce, validate and use an MHC-II tetramer, DRB1*07:01 APOB-p18, to sort APOB-p18-specific cells from peripheral blood mononuclear cell samples from 8 DRB1*07:01+ women with and without subclinical cardiovascular disease (sCVD). Single cell RNA sequencing showed that transcriptomes of tetramer+ cells were between regulatory and memory T cells in healthy women and moved closer to memory T cells in women with sCVD. TCR sequencing of tetramer+ cells showed clonal expansion and V and J segment usage similar to those found in regulatory T cells. These findings suggest that APOB-specific regulatory T cells may switch to a more memory-like phenotype in women with atherosclerosis. Mouse studies showed that such switched cells promote atherosclerosis.

Background Alterations in gut microbiota have been implicated in HIV infection and cardiovascular disease. However, how gut microbial alterations relate to host inflammation and metabolite profiles, and their relationships with atherosclerosis, have not been well-studied, especially in the context of HIV infection. Here, we examined associations of gut microbial species and functional components measured by shotgun metagenomics with carotid artery plaque assessed by B-mode carotid artery ultrasound in 320 women with or at high risk of HIV (65% HIV +) from the Women’s Interagency HIV Study. We further integrated plaque-associated microbial features with serum proteomics (74 inflammatory markers measured by the proximity extension assay) and plasma metabolomics (378 metabolites measured by liquid chromatography tandem mass spectrometry) in relation to carotid artery plaque in up to 433 women. Results Fusobacterium nucleatum, a potentially pathogenic bacteria, was positively associated with carotid artery plaque, while five microbial species (Roseburia hominis, Roseburia inulinivorans, Johnsonella ignava, Odoribacter splanchnicus, Clostridium saccharolyticum) were inversely associated with plaque. Results were consistent between women with and without HIV. Fusobacterium nucleatum was positively associated with several serum proteomic inflammatory markers (e.g., CXCL9), and the other plaque-related species were inversely associated with proteomic inflammatory markers (e.g., CX3CL1). These microbial-associated proteomic inflammatory markers were also positively associated with plaque. Associations between bacterial species (especially Fusobacterium nucleatum) and plaque were attenuated after further adjustment for proteomic inflammatory markers. Plaque-associated species were correlated with several plasma metabolites, including the microbial metabolite imidazole-propionate (ImP), which was positively associated with plaque and several pro-inflammatory markers. Further analysis identified additional bacterial species and bacterial hutH gene (encoding enzyme histidine ammonia-lyase in ImP production) associated with plasma ImP levels. A gut microbiota score based on these ImP-associated species was positively associated with plaque and several pro-inflammatory markers. Conclusion Among women living with or at risk of HIV, we identified several gut bacterial species and a microbial metabolite ImP associated with carotid artery atherosclerosis, which might be related to host immune activation and inflammation.

BackgroundThe perturbation of tryptophan (TRP)-kynurenine (KYN) metabolism has been linked with HIV infection and cardiovascular disease (CVD), but the interrelationship among TRP metabolites, gut microbiota, and atherosclerosis has not yet been fully understood in the context of HIV infection.MethodsWe included 361 women (241 HIV+, 120 HIV-) with carotid artery plaque assessments from the Women’s Interagency HIV Study, measured ten plasma TRP metabolites and profiled fecal gut microbiome. TRP metabolites related gut microbial features were selected through the Analysis of Compositions of Microbiomes with Bias Correction method. The associations of TRP metabolites and related microbial features with plaque were examined using multivariable logistic regression.ResultsWhile plasma kynurenic acid (KYNA) (odds ratio [OR]=1.93[1.12, 3.32] per one SD increase,P=0.02) and KYNA/TRP (OR=1.83[1.08, 3.09],P=0.02) were positively associated with plaque, indole-3-propionate (IPA) (OR=0.62 [0.40, 0.98],P=0.03) and IPA/KYNA (OR=0.51[0.33, 0.80],PRoseburia sp.,Eubacterium sp.,Lachnospira sp., andCoprobacter sp.; but no bacterial genera were found to be associated with KYNA. Furthermore, an IPA-associated-bacteria score was inversely associated with plaque (OR=0.47[0.28, 0.79],PConclusionsIn a cohort of women living with and without HIV infection, plasma IPA levels and related gut bacteria were inversely associated with carotid artery plaque, suggesting a potential beneficial role of IPA and its gut bacterial producers in atherosclerosis and CVD.

Hospitalizations among people living with HIV (PLWH) are frequent and costly. This study examined the association between psychiatric, HIV-related, and demographic factors and hospitalization rates among PLWH using data from the Einstein–Rockefeller-City University of New York Center for AIDS Research Clinical Cohort Database. Of the 10,215 PLWH included in the sample, 45% had at least one non-psychiatric hospitalization between 2009 and 2018, with significant risk factors including prior psychiatric outpatient visits, depression, or alcohol-related disorder diagnoses, female sex, older age, CD4 count

Chronic inflammation is associated with higher risk of cardiovascular disease (CVD) in people living with HIV (PLWH). We have previously shown that interleukin-32 (IL-32), a multi-isoform proinflammatory cytokine, is chronically upregulated in PLWH and is linked with CVD. However, the mechanistic roles of the different IL-32 isoforms in CVD are yet to be identified. In this study, we aimed to investigate the potential impact of IL-32 isoforms on coronary artery endothelial cells (CAEC), whose dysfunction represents a major factor for atherosclerosis. Our results demonstrated that the predominantly expressed IL-32 isoforms (IL-32β and IL-32γ) have a selective impact on the production of the proinflammatory cytokine IL-6 by CAEC. Furthermore, these two isoforms induced endothelial cell dysfunction by upregulating the expression of the adhesion molecules ICAM-I and VCAM-I and the chemoattractants CCL-2, CXCL-8 and CXCL-1. IL-32-mediated expression of these chemokines was sufficient to drive monocyte transmigration in vitro. Finally, we demonstrate that IL-32 expression in both PLWH and controls correlates with the carotid artery stiffness, measured by the cumulated lateral translation. These results suggest a role for IL-32-mediated endothelial cell dysfunction in dysregulation of the blood vessel wall and that IL-32 may represent a therapeutic target to prevent CVD in PLWH.

Introduction: Among 2-19-year-olds in the United States (US), 26.2% of Hispanic/Latino youth vs. 16.6% of non-Hispanic White youth experience obesity (body mass index [BMI] percentile ≥age- and sex-specific 95 th BMI percentile). While health behaviors are important, psychological and sociocultural measures vary across racial/ethnic groups and may underpin obesity disparities. Machine learning is one statistical approach that can be used to identify determinants of obesity. However, few studies have applied these methods to childhood obesity research, with most studies only examining traditional risk factors and creating a single model across all racial/ethnic groups. Our objective was to identify key predictors of BMI percentile in Hispanic/Latino youth to help design childhood obesity interventions that reduce health disparities. Hypothesis: We hypothesized that a BMI percentile prediction model developed for Hispanic/Latino youth would identify both traditional and novel risk factors as important determinants. Methods: Hispanic/Latino 8-16-year-olds from the 4 US sites of the Hispanic Community Children’s Health Study/Study of Latino Youth (SOL Youth) were examined ( n =1,466). BMI percentiles were determined via measured height and weight and CDC growth charts. A supervised machine learning approach, Least Absolute Shrinkage and Selection Operator (LASSO) regression, was used with BMI percentile as the outcome. There were 98 predictor variables examined spanning demographics; health behaviors; and environmental, psychological, and sociocultural measures. LASSO-selected variables were entered into a multivariable linear regression model to obtain effect estimates. P-values were adjusted for both multiple testing and the variable selection process and assessed with α Results: A LASSO model with 30 variables yielded the optimum mean squared error (MSE; R 2 =0.37), but a 12-variable solution was selected based on MSE and parsimony. Four associations were statistically significant. Perception of being larger than the “ideal” body weight (β=8.75 [95% CI: 8.21, 12.13]), reporting disordered eating (β=12.61 [95% CI: 10.64, 14.91]), and having a parent with obesity (β=4.90 [95% CI: 3.49, 17.75]) were associated with a higher BMI percentile. Spending >$5 weekly on snacks/beverages/fast food (β=-4.62 [95% CI: -19.18, -2.09]) was associated with a lower BMI percentile. Conclusions: Psychological and parental factors predicted higher BMI percentile and greater money spent on snacks/beverages/fast food predicted lower BMI percentile among Hispanic/Latino youth in the US. Addressing Hispanic/Latino youth’s relationships with food, body weight, and parents may be important in obesity interventions. Longitudinal research is needed to clarify directionality and replicate novel findings.

Insulin resistance is hypothesized to contribute to increases in blood pressure (BP) through both the renin-angiotensin-aldosterone and sympathetic nervous systems. Prior large-scale studies examining this association are confounded by overt diabetes, obesity, and antihypertensive medication use. In a cross-sectional analysis of 10 810 HCHS/SOL (Hispanic Community Health Study/Study of Latinos) participants without diabetes and not taking antihypertensive medications, we examined the associations of insulin resistance, quantified by homeostasis model assessment of insulin resistance (HOMA-IR), with systolic BP (SBP) and diastolic BP overall and stratified by sex and prediabetes status in unadjusted and adjusted analyses. The total sample included 52% women; mean (SD) age, 37.2 (13.4) years; 39% of participants had prediabetes (mean [SD] HOMA-IR, 2.8 [2.2]). Stage 1 or 2 hypertension was present in 26% of participants (mean [SD] SBP, 116.8 [15] mm Hg and diastolic BP, 71.0 [10.4] mm Hg). Overall, there was a significant linear association between HOMA-IR and both SBP (β, 2.64±0.44) and diastolic BP (β, 1.49±0.35). We found a significant interaction with sex and the association between HOMA-IR and SBP; the association was linear in men and nonlinear in women. There was no statistically significant interaction between prediabetes status and the associations between HOMA-IR and BP. In conclusion, in a large community-based sample of Hispanic/Latino adults of diverse national backgrounds not taking antihypertensive medications and free from diabetes, insulin resistance was positively associated with both SBP and diastolic BP. Future longitudinal studies, with adequate power to examine sex-specific differences, are needed to examine the independent contribution of insulin resistance to the development of hypertension.

Background Cryopreserved peripheral blood mononuclear cells (PBMCs) are frequently collected and provide disease- and treatment-relevant data in clinical studies. Here, we developed combined protein (40 antibodies) and transcript single-cell (sc)RNA sequencing (scRNA-seq) in PBMCs. Results Among 31 participants in the Women’s Interagency HIV Study (WIHS), we sequenced 41,611 cells. Using Boolean gating followed by Seurat UMAPs (tool for visualizing high-dimensional data) and Louvain clustering, we identified 50 subsets among CD4+ T, CD8+ T, B, NK cells, and monocytes. This resolution was superior to flow cytometry, mass cytometry, or scRNA-seq without antibodies. Combined protein and transcript scRNA-seq allowed for the assessment of disease-related changes in transcriptomes and cell type proportions. As a proof-of-concept, we showed such differences between healthy and matched individuals living with HIV with and without cardiovascular disease. Conclusions In conclusion, combined protein and transcript scRNA sequencing is a suitable and powerful method for clinical investigations using PBMCs.

Summary In women with HIV, higher activation and exhaustion of CD4+ T cells were associated with risk of non-HIV-related mortality during a median of 13.3 years of follow-up, independent of baseline demographic, behavioral, HIV-related, and cardiometabolic factors and longitudinal HIV disease progression. Background Dysregulation of adaptive immunity is a hallmark of human immunodeficiency virus (HIV) infection that persists on antiretroviral therapy (ART). Few long-term prospective studies have related adaptive immunity impairments to mortality in HIV, particularly in women. Methods Among 606 women with HIV in the Women’s Interagency HIV Study, peripheral blood mononuclear cells collected from 2002 to 2005 underwent multiparameter flow cytometry. Underlying cause of death was ascertained from the National Death Index up to 2018. We examined associations of CD4+ and CD8+ T-cell activation (%CD38+HLA-DR+), senescence (%CD57+CD28–), exhaustion (%PD-1+), and nonactivation/normal function (%CD57–CD28+) with natural-cause, HIV-related, and non-HIV-related mortality. Results At baseline, median participant age was 41, and 67% were on ART. Among 100 deaths during a median of 13.3 years follow-up, 90 were natural-cause (53 non-HIV-related, 37 HIV-related). Higher activation and exhaustion of CD4+ T cells were associated with risk of natural-cause and non-HIV-related mortality, adjusting for age, demographic, behavioral, HIV-related, and cardiometabolic factors at baseline. Additional adjustment for time-varying viral load and CD4+ T-cell count did not attenuate these associations. CD8+ T-cell markers were not associated with any outcomes adjusting for baseline factors. Conclusions Persistent CD4+ T-cell activation and exhaustion may contribute to excess long-term mortality risk in women with HIV, independent of HIV disease progression.

BACKGROUND: Data on clinical characteristics and outcomes of people living with HIV (PLWH) hospitalized with coronavirus disease 2019 (COVID-19) who develop acute kidney injury (AKI) are limited. SETTING: Large tertiary health care system in the Bronx, NY. METHODS: We performed a retrospective cohort study of 83 PLWH and 4151 patients without HIV hospitalized with COVID-19 from March 10, 2020, to May 11, 2020. We compared the clinical characteristics and outcomes associated with AKI by HIV serostatus and evaluated HIV-related factors for AKI among PLWH. AKI was defined and staged using Kidney Disease Improving Global Outcomes criteria. RESULTS: The incidence of AKI in hospitalized patients with COVID-19 did not differ significantly by HIV serostatus (54.2% in PLWH vs 49.5% in patients without HIV, P = 0.6). Despite a higher incidence of stage 3 AKI (28.9% vs 17.1% P = 0.05) in PLWH compared with those without HIV, there was no significant difference in the need for renal replacement therapy (22.2% vs 13.4% P = 0.12), renal recovery (76.9% vs 82.5% P = 0.61), or dependence on renal replacement therapy (7.7% vs 3.8% P = 0.27). CD4 T-cell count, HIV-1 RNA viral suppression, and antiretroviral therapy use were not associated with AKI. AKI was associated with increased need for invasive ventilation and in-hospital death, but HIV was not an independent risk factor of in-hospital death after AKI [adjusted hazard ratio 1.01 (95% CI: 0.59 to 1.72), P = 0.98]. CONCLUSIONS: HIV-related factors were not associated with increased risk of AKI in PLWH hospitalized with COVID-19. PLWH hospitalized with COVID-19 had more stage 3 AKI, but outcomes after AKI were similar to those without HIV.

BACKGROUND Persistent inflammation in HIV infection is associated with elevated cardiovascular disease (CVD) risk, even with viral suppression. Identification of novel surrogate biomarkers can enhance CVD risk stratification and suggest novel therapies. We investigated the potential of interleukin 32 (IL-32), a proinflammatory multi-isoform cytokine, as a biomarker for subclinical carotid artery atherosclerosis in virologically suppressed women living with HIV (WLWH). METHODS AND RESULTS Nested within the Women's Interagency HIV Study, we conducted a cross-sectional comparison of IL-32 between 399 WLWH and 100 women without HIV, followed by a case-control study of 72 WLWH (36 carotid artery plaque cases vs. 36 age-matched controls without plaque). Plasma IL-32 protein was measured by ELISA, and mRNA of IL-32 isoforms (IL-32α, β, γ, D, e, and θ) was quantified by reverse transcription polymerase chain reaction from peripheral blood mononuclear cells. Plasma IL-32 protein levels were higher in WLWH compared with women without HIV (P = 0.02). Among WLWH, although plasma IL-32 levels did not differ significantly between plaque cases and controls, expression of IL-32 isoforms α, β, and e mRNA was significantly higher in peripheral blood mononuclear cells from cases (P = 0.01, P = 0.005, and P = 0.018, respectively). Upregulation of IL-32β and IL-32e among WLWH with carotid artery plaque persisted after adjustment for age, race/ethnicity, smoking, systolic blood pressure, body mass index, and history of hepatitis C virus (P = 0.04 and P = 0.045); the adjusted association for IL-32α was marginally significant (P = 0.07). CONCLUSIONS IL-32 isoforms should be studied further as potential CVD biomarkers. This is of particular interest in WLWH by virtue of altered IL-32 levels in this population.

PURPOSE: HIV research among transgender and gender nonbinary (TGNB) people is limited by lack of gender identity data collection. We designed an EHR-based algorithm to identify TGNB people among patients living with HIV (PLWH) when gender identity was not systematically collected. METHODS: We applied EHR-based search criteria to all PLWH receiving care at a large urban health system between 1997–2017, then confirmed gender identity by chart review. We compared patient characteristics by gender identity and screening criteria, then calculated positive predictive values (PPVs) for each criterion. RESULTS: Among 18,086 PLWH, 213 (1.2%) met criteria as potential TGNB patients and 178/213 were confirmed. PPVs were highest for free-text keywords (91.7%) and diagnosis codes (77.4%). Verified TGNB patients were younger (median 32.5 vs. 42.5 years, p

Background Food insecurity is associated with increased morbidity and mortality in people with human immunodeficiency virus (HIV) on antiretroviral therapy, but its relationship with immune dysregulation, a hallmark of HIV infection and comorbidity, is unknown. Methods In 241 women participating in the Women’s Interagency HIV Study, peripheral blood mononuclear cells were characterized by flow cytometry to identify cell subsets, comprising surface markers of activation (%CD38+HLADR+), senescence (%CD57+CD28−), exhaustion (%PD-1+), and co-stimulation (%CD57− CD28+) on CD4+ and CD8+ T cells. Mixed-effects linear regression models were used to assess the relationships of food insecurity with immune outcomes, accounting for repeated measures at ≤3 study visits and adjusting for sociodemographic and clinical factors. Results At the baseline study visit, 71% of participants identified as non-Hispanic Black, 75% were virally suppressed, and 43% experienced food insecurity. Food insecurity was associated with increased activation of CD4+ and CD8+ T cells, increased senescence of CD8+ T cells, and decreased co-stimulation of CD4+ and CD8+ T cells (all P 40 copies/mL and CD4 Conclusions Food insecurity may contribute to the persistent immune activation and senescence in women with HIV on antiretroviral therapy, independently of HIV control. Reducing food insecurity may be important for decreasing non–AIDS-related disease risk in this population.

BackgroundHIV and HCV have been linked to an increased risk of cardiovascular disease (CVD). Their impact on long-term outcomes following ST-segment myocardial infarction (STEMI) has not been previously studied.MethodsWe leveraged data from a STEMI registry (n=1208) at an inner-city health system to assess the influence of HIV and HCV on post-STEMI outcomes. Cox regression was used to compare HIV-monoinfected (n=22), HCV-monoinfected (n=26) and HIV-HCV-coinfected patients (n=8) with the neither-infected group (n=1152) with regard to death, death or any readmission, and death or CVD readmission.ResultsThe cohort was majority black or Hispanic. Median follow-up was 4.3 years. Compared to the neither-infected group, the HIV-monoinfected group showed near-significantly higher risks of death or any readmission (HR=1.62, 95% CI=0.96, 2.74) and death or CVD readmission (HR=1.82, 95% CI=0.98, 3.39) after full adjustment. On similar comparison, the HCV-monoinfected group exhibited significantly higher risks of death (HR=2.09, 95% CI=1.05, 4.15) and death or any readmission (HR=1.68, 95% CI=1.07, 2.65), whereas the HIV-HCV-coinfected group showed higher risk of death (HR=6.51, 95% CI=2.28, 18.61).ConclusionsIn this cohort composed mostly of race-ethnic minorities, HIV monoinfection tended to be associated with 1.6-to-1.8-fold higher risk of death or readmission for any cause or CVD over long-term follow-up compared to neither infection, whereas HCV monoinfection was associated with 1.7-to-2.1-fold higher risk of death and death or any readmission, and HIV-HCV coinfection with 6.5-fold higher risk of death. These associations require further study in larger populations, but highlight the importance of identifying and treating HIV and HCV in patients presenting with STEMI.

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.

Using a tool integrated into the electronic health record, we determined prevalence of 10 social needs among 377 people with HIV (PWH) and 27,833 patients without HIV receiving care in the Montefiore Health System. PWH (median age 53) were 55% women, 41% Black, 44% Hispanic. 33% of PWH reported at least one social need vs. 18% among patients without HIV, with healthcare transportation and housing needs significantly higher in PWH in adjusted analyses. PWH reporting transportation needs were 27% less likely to be virologically suppressed (

Using a tool integrated into the electronic health record, we determined prevalence of 10 social needs among 377 people with HIV (PWH) and 27,833 patients without HIV receiving care in the Montefiore Health System. PWH (median age 53) were 55% women, 41% Black, 44% Hispanic. 33% of PWH reported at least one social need vs. 18% among patients without HIV, with healthcare transportation and housing needs significantly higher among PWH in adjusted analyses. PWH reporting transportation needs were 27% less likely to be virologically suppressed ( 200 copies/mL, adjusted prevalence ratio 0.73, 95% CI 0.55-0.96) compared with PWH without transportation needs.Por medio del uso de encuestas integradas en el registro electrónico de salud, determinamos la prevalencia de 10 necesidades sociales entre 377 personas con VIH (PCV) y 27 833 pacientes sin VIH que reciben atención en el Montefiore Health System. PCV (edad mediana de 53 años) fueron 55% mujeres, 41% negras, 44% hispanas. 33% de PCV reportó al menos una necesidad social vs. 18% de los pacientes sin VIH, siendo las necesidades de transporte a cuidados de salud y de vivienda significativamente mayores en PCV en análisis multivariable ajustado. PCV con necesidades de transportación fueron 27% menos probables de tener supresión viral ( 200 copias/ml, razón de prevalencias ajustada 0.73, IC 95% 0.55–0.96) comparada con PCV sin necesidades de transportación.

We examined associations of micro-scale environment attributes (e.g., sidewalks, street crossings) with three physical activity (PA) measures among Hispanic/Latino adults (n = 1776) living in San Diego County, CA. Systematic observation was used to quantify micro-scale environment attributes near each participant's home. Total PA was assessed with accelerometers, and PA for transportation and recreation were assessed by validated self-report. Although several statistically significant interactions between individual and neighborhood characteristics were identified, there was little evidence micro-scale attributes were related to PA. An important limitation was restricted environmental variability for this sample which lived in a small area of a single county.

In response to the opioid overdose crisis in the United States, many states implemented policies to guide opioid prescribing, but their impact on overdose mortality (prescription and non-prescription) remains poorly understood. We examined the impact of U.S. state opioid-prescribing policies on opioid overdose mortality following implementation.We calculated opioid overdose mortality rates from 1999-2016 by U.S. state using the CDC WONDER database, overall and separately for overdose deaths from prescription and non-prescription opioids. For each state, policies active on 1/1/2014 were reviewed for the presence and strength of six provisions recommending judicious opioid prescribing practices; "strong" provisions used the words "should," "shall," or "must". Interrupted time series (ITS) tested the association of each strong provision with overdose mortality, overall and separately for prescription and non-prescription opioids, in the two years following implementation. Sensitivity analyses compared between states, used time-lagged analyses, and excluded synthetic opioids from non-prescription opioid deaths.All six provisions had consistent direction of effect in ITS and sensitivity analyses. Strong provisions for prescriber training and limits on opioid dose reduced the slope of overall and prescription opioid overdose mortality in both ITS and sensitivity analyses. Reduced non-prescription opioid overdose mortality was only associated with strong provision for prescriber training. Some provisions had a negative impact. In ITS, strong provision for prescriber response to misuse increased the slope of non-prescription opioid overdose mortality. Strong provision for mandatory prescription drug monitoring program use had no relationship with overdose mortality in ITS and was associated with increased overall, prescription and non-prescription opioid overdose mortality in between-state sensitivity analysis.Opioid prescribing policies in U.S. states at the peak of the prescription opioid epidemic had modest mortality benefit, and did not reduce non-prescription opioid overdose mortality. A strong provision for prescriber training was the only provision associated with reduced prescription and non-prescription opioid overdose mortality. These findings can inform future efforts addressing prescription drug epidemics.

Transgender women (transwomen) are frequently conflated with cisgender sexual minority men (cis-SMM) in HIV research. We examined the impact of socioeconomic and health conditions, and gender-affirming hormones in comparing HIV-related outcomes between cis-SMM and transwomen.Large tertiary care health system in the Bronx, NY.Retrospective cohort study of people with HIV receiving care in 2008-2017. We compared retention in care, antiretroviral therapy (ART) prescription, and viral suppression between cis-SMM and transwomen, using modified Poisson regression, adjusting for demographic and clinical factors. Transwomen were further stratified by receipt of estrogen prescription.We included 166 transwomen (1.4%), 1936 cis-SMM (17%), 4715 other cisgender men (41%), and 4745 cisgender women (41%). Transwomen were more likely to have public insurance (78% vs 65%) and mental health (49% vs 39%) or substance use (43% vs 33%) diagnoses than cis-SMM. Compared with cis-SMM, transwomen prescribed estrogen (67% of transwomen) were more likely to be retained [adjusted risk ratio (aRR) 1.15, 95% confidence interval (CI) 1.08 to 1.23), prescribed ART (aRR 1.06, CI 1.01 to 1.11), and virally suppressed (aRR 1.08, CI 1.01 to 1.16). Transwomen not prescribed estrogen were less likely to be retained (aRR 0.92, CI 0.83 to 1.02), prescribed ART (aRR 0.90, CI 0.82 to 0.98), or virally suppressed (aRR 0.85, CI 0.76 to 0.95).In the context of HIV, socioeconomic factors, comorbidities, and gender-affirming care distinguish transwomen from cis-SMM. Compared with cis-SMM, transwomen who were prescribed estrogen had better HIV care continuum outcomes; transwomen not prescribed estrogen had worse outcomes. These differences should be accounted for in HIV-related research.

Current U.S. dietary guidelines recommend a daily potassium intake of 3400 mg/day for men and 2600 mg/day for women. Sub-optimal access to nutrient-rich foods may limit potassium intake and increase cardiometabolic risk. We examined the association of neighborhood characteristics related to food availability with potassium intake in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL). 13,835 participants completed a 24-h dietary recall assessment and had complete covariates. Self-reported potassium intake was calibrated with an objective 24-h urinary potassium biomarker, using equations developed in the SOL Nutrition &amp, Physical Activity Assessment Study (SOLNAS, N = 440). Neighborhood population density, median household income, Hispanic/Latino diversity, and a retail food environment index by census tract were obtained. Linear regression assessed associations with 24-h potassium intake, adjusting for individual-level and neighborhood confounders. Mean 24-h potassium was 2629 mg/day based on the SOLNAS biomarker and 2702 mg/day using multiple imputation and HCHS/SOL biomarker calibration. Compared with the lowest quartile of neighborhood population density, living in the highest quartile was associated with a 26% lower potassium intake in SOLNAS (adjusted fold-change 0.74, 95% CI 0.59–0.94) and a 39% lower intake in HCHS/SOL (adjusted fold-change 0.61 95% CI 0.45–0.84). Results were only partially explained by the retail food environment. The mechanisms by which population density affects potassium intake should be further studied.

Objective: Daily tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) use as HIV preexposure prophylaxis (PrEP) is monitored by identifying TDF/FTC prescriptions from pharmacy databases and applying diagnosis codes and antiretroviral data to algorithms that exclude TDF/FTC prescribed for HIV postexposure prophylaxis (PEP), HIV treatment, and hepatitis B virus (HBV) treatment. We evaluated the accuracy of 3 algorithms used by the Centers for Disease Control and Prevention (CDC), Gilead Sciences, and the New York State Department of Health (NYSDOH) using a reference population in Bronx, New York. Methods: We extracted diagnosis codes and data on all antiretroviral prescriptions other than TDF/FTC from an electronic health record database for persons aged ≥16 prescribed TDF/FTC during July 2016–June 2018 at Montefiore Medical Center. We reviewed medical records to classify the true indication of first TDF/FTC use as PrEP, PEP, HIV treatment, or HBV treatment. We applied each algorithm to the reference population and compared the results with the medical record review. Results: Of 2862 patients included in the analysis, 694 used PrEP, 748 used PEP, 1407 received HIV treatment, and 13 received HBV treatment. The algorithms had high specificity (range: 98.4%-99.0%), but the sensitivity of the CDC algorithm using a PEP definition of TDF/FTC prescriptions ≤30 days was lower (80.3%) than the sensitivity of the algorithms developed by Gilead Sciences (94.7%) or NYSDOH (96.1%). Defining PEP as TDF/FTC prescriptions ≤28 days improved CDC algorithm performance (sensitivity, 95.8%; specificity, 98.8%). Conclusions: Adopting the definition of PEP as ≤28 days of TDF/FTC in the CDC algorithm should improve the accuracy of national PrEP surveillance.

C1q/tumor necrosis factor (TNF)-related proteins (CTRPs) have been linked to energy homeostasis and vascular health. People with HIV are susceptible to cardiometabolic disease, but the contributions of different CTRPs are unknown. We investigated the associations of HIV and related factors with serum CTRPs, and CTRPs' relationships with cardiometabolic phenotypes. This involved a cross-sectional analysis of participants in the Women's Interagency HIV Study aged ≥35 with (n = 209) and without (n = 92) HIV who underwent carotid ultrasound in 2004–2005 and had stored serum available for measurement of total adiponectin and CTRPs 1, 3, 5, and 9. The Benjamini/Hochberg procedure was used to control the study-wide false-positive rate. HIV-positive women had significantly higher adiponectin than HIV-negative women after adjustment for sociodemographic, behavioral, and clinical variables [beta = 0.29 (95% confidence interval 0.11–0.47)]. Among HIV-positive women, lower CD4 count was associated with higher adiponectin and history of AIDS with higher CTRP9, but these were only nominally significant. There was no relationship between HIV status and CTRP 1, 3, or 5, nor was antiretroviral therapy or viral load associated with any CTRP. In the entire cohort, higher adiponectin was associated with significantly lower fasting glucose and insulin resistance, while higher CTRP5 [beta = -0.02 (−0.033 to −0.007)]—and, at a nominal level, CTRPs 1 and 3—was associated with significantly lower carotid intima-media thickness. In conclusion, in this sample of middle-aged women, HIV serostatus was positively associated with adiponectin, but not CTRPs. In turn, serum adiponectin was inversely associated with glucose dysregulation, whereas CTRP5 was inversely associated with carotid intima-media thickness. Further research is needed to determine CTRPs' role in atherosclerosis.

Background Human immunodeficiency virus (HIV) may affect the risk of death due to cardiovascular disease (CVD) differently in men versus women. Methods We examined CVD mortality rates between 2007 and 2017 among all New York City residents living with HIV and aged 13+ by sex, using data from city HIV surveillance and vital statistics and the National Death Index. Residents without HIV were enumerated using modified US intercensal estimates. We determined associations of HIV status with CVD mortality by sex and neighborhood poverty, defined as the percent of residents living below the federal poverty level, after accounting for age, race/ethnicity, and year. Results There were 3234 CVD deaths reported among 147 915 New Yorkers living with HIV, with the proportion of deaths due to CVD increasing from 11% in 2007 to 22% in 2017. The age-standardized CVD mortality rate was 2.7/1000 person-years among both men and women with HIV. The relative rate of CVD mortality associated with HIV status was significantly higher among women (adjusted rate ratio [aRR] 1.7, 95% confidence interval [CI] 1.6–1.8) than men (aRR 1.2, 95% CI 1.1–1.3) overall, and within strata defined by neighborhood poverty. Sex differences in CVD mortality rates were the greatest when comparing individuals living with HIV and having detectable HIV RNA and CD4+ T-cell counts Conclusions Among people with HIV, 1 in 5 deaths is now associated with CVD. HIV providers should recognize the CVD risk among women with HIV, and reinforce preventive measures (eg, smoking cessation, blood pressure control, lipid management) and viremic control among people living with HIV regardless of neighborhood poverty to reduce CVD mortality. Human immunodeficiency virus (HIV) increases cardiovascular disease mortality risks to a greater degree among women than men, even after accounting for neighborhood poverty. HIV providers should emphasize cardiovascular disease prevention (eg, smoking cessation, hypertension control, lipid management) and viremic control.

BACKGROUND High sodium and low potassium consumption are risk factors for hypertension. The objectives of this study were to describe usual daily intake of sodium and potassium among US Hispanics/Latinos of diverse background groups and estimate the proportion meeting guidelines for dietary sodium and potassium intake. METHODS We studied 16,171 participants of the Hispanic Community Health Study/Study of Latinos (HCHS/SOL), a diverse group of self-identified Hispanics/Latinos aged 18–74 years from 4 US communities. In 2008–2011, all HCHS/SOL participants underwent a standardized examination. Median usual daily intake of dietary sodium and potassium were derived from two 24-hour diet recalls; standard errors and 95% confidence intervals (CIs) were calculated using boot strap methods. Meeting 2015 US Department of Agriculture guidelines was defined as an intake of RESULTS Among US Hispanics/Latinos, median usual daily intake of sodium was 2,574 mg (95% CI: 2,547, 2,600) among women and 3,747 mg (95% CI: 3,697, 3,796) among men. Median usual daily intake of potassium was 2,069 mg (95% CI: 2,046, 2,092) among women and 2,649 mg (95% CI: 2,615, 2,683) among men. Overall, only 21.3% (95% CI: 20.2%, 22.4%) of the US Hispanic/Latino population met 2015 recommendations for sodium and 0.6% (95% CI: 0.4%, 0.8%) for potassium. CONCLUSIONS Among US Hispanics/Latinos intake of sodium is too high and potassium too low. Strategies to reduce sodium intake while simultaneously increasing intake of potassium in this US population are warranted.

HIV and HCV have each been linked with cardiac dysfunction. Studies of HIV have often lacked appropriate controls and primarily involved men, whereas data for HCV are sparse.We performed repeat echocardiography over a median interval of 12 years in participants from the Women's Interagency HIV Study in order to evaluate the relationships of HIV and HCV with incident left ventricular (LV) dysfunction (systolic or diastolic).Of the 311 women included (age 39 ± 9), 70% were HIV-positive and 20% HCV-positive. Forty three participants (13.8%) developed LV dysfunction, of which 79.1% was diastolic. Compared with participants with neither infection, the group with HIV--HCV coinfection showed a significantly increased risk of incident LV dysfunction after adjustment for risk factors [RR = 2.96 (95% CI = 1.05-8.31)], but associations for the HCV monoinfected and HIV monoinfected groups were not statistically significant [RR = 2.54 (0.83-7.73) and RR = 1.66 (0.65-4.25), respectively]. Comparison of HCV-positive and HCV-negative women showed a significantly increased risk independent of covariates [RR = 1.96 (1.02-3.77)] but this was not the case for HIV-positive vs. HIV-negative women [RR = 1.43 (0.76-2.69)]. There was no evidence of HCV-by-HIV interaction. A more restrictive definition of LV diastolic dysfunction led to fewer incident cases, but a similar, though nonsignificant, risk estimate for HCV.Among mostly middle-aged women, HCV but not HIV infection was associated with a pronounced risk of incident LV dysfunction. Although the influence of residual confounding cannot be excluded, these findings bolster the potential benefits that could be realized by adopting recent recommendations for expanding HCV screening and treatment.

Despite the success of antiretroviral therapy (ART), people living with HIV (PLWH) are still at higher risk for cardiovascular diseases (CVDs) that are mediated by chronic inflammation. Identification of novel inflammatory mediators with the inherent potential to be used as CVD biomarkers and also as therapeutic targets is critically needed for better risk stratification and disease management in PLWH. Here, we investigated the expression and potential role of the multi-isoform proinflammatory cytokine IL-32 in subclinical atherosclerosis in PLWH (n=49 with subclinical atherosclerosis and n=30 without) and HIV- controls (n=25 with subclinical atherosclerosis and n=24 without). While expression of all tested IL-32 isoforms (α, β, γ, D, ϵ, and θ) was significantly higher in peripheral blood from PLWH compared to HIV- controls, IL-32D and IL-32θ isoforms were further upregulated in HIV+ individuals with coronary artery atherosclerosis compared to their counterparts without. Upregulation of these two isoforms was associated with increased plasma levels of IL-18 and IL-1β and downregulation of the atheroprotective protein TRAIL, which together composed a unique atherosclerotic inflammatory signature specific for PLWH compared to HIV- controls. Logistic regression analysis demonstrated that modulation of these inflammatory variables was independent of age, smoking, and statin treatment. Furthermore, our in vitro functional data linked IL-32 to macrophage activation and production of IL-18 and downregulation of TRAIL, a mechanism previously shown to be associated with impaired cholesterol metabolism and atherosclerosis. Finally, increased expression of IL-32 isoforms in PLWH with subclinical atherosclerosis was associated with altered gut microbiome (increased pathogenic bacteria; Rothia and Eggerthella species) and lower abundance of the gut metabolite short-chain fatty acid (SCFA) caproic acid, measured in fecal samples from the study participants. Importantly, caproic acid diminished the production of IL-32, IL-18, and IL-1β in human PBMCs in response to bacterial LPS stimulation. In conclusion, our studies identified an HIV-specific atherosclerotic inflammatory signature including specific IL-32 isoforms, which is regulated by the SCFA caproic acid and that may lead to new potential therapies to prevent CVD in ART-treated PLWH.

BACKGROUND HIV and HCV have each been linked with cardiac dysfunction. Studies of HIV have often lacked appropriate controls and primarily involved men, whereas data for HCV are sparse. METHODS We performed repeat echocardiography over a median interval of 12 years in participants from the Women's Interagency HIV Study in order to evaluate the relationships of HIV and HCV with incident left ventricular (LV) dysfunction (systolic or diastolic). RESULTS Of the 311 women included (age 39 ± 9), 70% were HIV-positive and 20% HCV-positive. Forty three participants (13.8%) developed LV dysfunction, of which 79.1% was diastolic. Compared with participants with neither infection, the group with HIV--HCV coinfection showed a significantly increased risk of incident LV dysfunction after adjustment for risk factors [RR = 2.96 (95% CI = 1.05-8.31)], but associations for the HCV monoinfected and HIV monoinfected groups were not statistically significant [RR = 2.54 (0.83-7.73) and RR = 1.66 (0.65-4.25), respectively]. Comparison of HCV-positive and HCV-negative women showed a significantly increased risk independent of covariates [RR = 1.96 (1.02-3.77)] but this was not the case for HIV-positive vs. HIV-negative women [RR = 1.43 (0.76-2.69)]. There was no evidence of HCV-by-HIV interaction. A more restrictive definition of LV diastolic dysfunction led to fewer incident cases, but a similar, though nonsignificant, risk estimate for HCV. CONCLUSION Among mostly middle-aged women, HCV but not HIV infection was associated with a pronounced risk of incident LV dysfunction. Although the influence of residual confounding cannot be excluded, these findings bolster the potential benefits that could be realized by adopting recent recommendations for expanding HCV screening and treatment.

Machine learning is a class of algorithms able to handle a large number of predictors with potentially nonlinear relationships. By applying machine learning to obesity, researchers can examine how risk factors across multiple settings (e.g., school and home) interact to best predict childhood obesity risk. In this narrative review, we provide an overview of studies that have applied machine learning to predict childhood obesity using a combination of sociodemographic and behavioral risk factors. The objective is to summarize the key determinants of obesity identified in existing machine learning studies and highlight opportunities for future machine learning applications in the field. Of 15 peer-reviewed studies, approximately half examined early childhood (0-24 months of age) determinants. These studies identified child's weight history (e.g., history of overweight/obesity or large increases in weight-related measures between birth and 24 months of age) and parental overweight/obesity (current or prior) as key risk factors, whereas the remaining studies indicated that social factors and physical inactivity were important in middle childhood and late childhood/adolescence. Across age groups, findings suggested that race/ethnic-specific models may be needed to accurately predict obesity from middle childhood onward. Future studies should consider using existing large data sets to take advantage of the benefits of machine learning and should collect a wider range of novel risk factors (e.g., psychosocial and sociocultural determinants of health) to better predict childhood obesity. Ultimately, such research can aid in the development of effective obesity prevention interventions, particularly ones that address the disproportionate burden of obesity experienced by racial/ethnic minorities.

Background Presence of cardiovascular disease (CVD) risk factors (RFs) should prompt patients and their providers to work aggressively towards controlling those that are modifiable. The extent to which a greater CVD RF burden is related to CVD RF control in a contemporary and diverse Hispanic/Latino population is not well-understood. Methods Using multicenter community-based data from the Hispanic Community Health Study/Study of Latinos, we assessed the self-reported prevalence of hypertension, hypercholesterolemia, diabetes, and prevalent CVD (ischemic heart disease or stroke). We used contemporaneous guidelines to define RF control. Multivariable logistic regression for complex survey sampling was used to examine whether having more CVD RFs was associated with CVD RF control (adjusting for age, sex, Hispanic background group, education, and health insurance). Results Our sample included 8521 participants with at least one CVD RF or prevalent CVD. The mean age in HCHS/SOL target population was 49 (SE 0.3) years and 56% were women. Frequency of one, two, or three self-reported CVD RFs was 57%, 26%, 8%, respectively, and overall 9% of participants had prevalent CVD. After adjusting for sociodemographic factors, compared to those reporting one CVD RF, individuals with three CVD RFs were the least likely to have blood pressure, cholesterol, and glucose optimally controlled (odds ratio [OR]: 0.56; 95% confidence interval [CI]: 0.40–0.80). However, those with prevalent CVD were more likely to have all three risk factors controlled, (OR: 1.43; 95% CI: 1.01–2.01). Conclusion Hispanic/Latino adults with three major CVD RFs represent a group with poor overall CVD RF control. Secondary CVD prevention fares better. The potential contributors to inadequate CVD RF control in this highly vulnerable group warrants further investigation.

ObjectivesAntiretroviral therapy (ART) use is associated with disrupted lipid and glucose metabolism in people with HIV-infection. We aimed to identify plasma lipid species associated with risk of diabetes in the context of HIV infection.Research Design and MethodsWe profiled 211 plasma lipid species in 491 HIV-infected and 203 HIV-uninfected participants aged 35-55 years from the Women’s Interagency HIV study and the Multicenter AIDS Cohort Study. Cox proportional hazards model was used to examine associations between baseline lipid species and incident diabetes (166 diabetes cases were identified during a median follow-up of 12.6 years).ResultsWe identified 11 lipid species, representing independent signals for 8 lipid classes/subclasses, associated with risk of diabetes (PConclusionsThis study identified multiple plasma lipid species associated with incident diabetes. Regardless of the directions of their associations with diabetes, most diabetes-associated lipid species were elevated in ART-treated people with HIV-infection. This suggests a complex role of lipids in the link between ART and diabetes in HIV infection.

Cryopreserved peripheral blood mononuclear cells (PBMCs) are frequently collected and provide disease- and treatment-relevant data in clinical studies. Here, we developed combined protein (40 antibodies) and transcript single cell (sc)RNA sequencing in PBMCs. Among 31 participants in the WIHS Study, we sequenced 41,611 cells. Using Boolean gating followed by Seurat UMAPs and Louvain clustering, we identified 58 subsets among CD4 T, CD8 T, B, NK cells and monocytes. This resolution was superior to flow cytometry, mass cytometry or scRNA-sequencing without antibodies. Since the transcriptome was not needed for cell identification, combined protein and transcript scRNA-Seq allowed for the assessment of disease-related changes in transcriptomes and cell type proportion. As a proof-of-concept, we showed such differences between healthy and matched individuals living with HIV with and without cardiovascular disease. In conclusion, combined protein and transcript scRNA sequencing is a suitable and powerful method for clinical investigations using PBMCs.

Aims During virally suppressed chronic HIV infection, persistent inflammation contributes to the development of cardiovascular disease (CVD), a major comorbidity in people living with HIV (LWH). Classical blood monocytes (CMs) remain activated during antiretroviral therapy and are a major source of pro-inflammatory and pro-thrombotic factors that contribute to atherosclerotic plaque development and instability. Methods and results Here, we identify transcriptomic changes in circulating CMs in peripheral blood mononuclear cell samples from participants of the Women’s Interagency HIV Study, selected by HIV and subclinical CVD (sCVD) status. We flow-sorted CM from participants of the Women’s Interagency HIV Study and deep-sequenced their mRNA (n = 92). CMs of HIV+ participants showed elevated interleukin (IL)-6, IL-1β, and IL-12β, overlapping with many transcripts identified in sCVD+ participants. In sCVD+ participants LWH, those reporting statin use showed reduced pro-inflammatory gene expression to a level comparable with healthy (HIV−sCVD−) participants. Statin non-users maintained an elevated inflammatory profile and increased cytokine production. Conclusion Statin therapy has been associated with a lower risk of cardiac events, such as myocardial infarction in the general population, but not in those LWH. Our data suggest that women LWH may benefit from statin therapy even in the absence of overt CVD.

Objectives: Nonclassical monocytes (NCM) have patrolling functions relevant to atherosclerosis. While NCM have low surface CXCR4 expression in people with concurrent HIV and CVD (Mueller Cardiovasc Res 2019), the extent of CVD-related gene expression and the pathways involved are unknown. We described the gene transcription signature of NCM to provide insight into potential mechanisms of HIV-associated CVD. Methods: We identified transcriptomic changes in circulating NCM among women with and without chronic HIV infection. CVD was defined by plaques found on B-mode carotid artery ultrasound. The study included 23 HIV - CVD - , 21 HIV + CVD - , 20 HIV - CVD + , and 21 HIV + CVD + women, with these four groups matched by age (median = 45), race (95% minority) and smoking (86% ever-smokers). Using cryopreserved cells, we flow-sorted NCM (CD14 dim CD16+) and deep-sequenced their mRNA (average depth >40 million reads) to identify differentially expressed genes (DEG) contrasting HIV alone, CVD alone, and concurrent HIV + CVD + groups, versus HIV - CVD - , based on FDR-adjusted P Results: After filtering to genes with raw counts >10 in >60% of participants, 11,343 protein coding genes were analyzed. HIV alone was associated with 10 DEGs on NCM (Figure). Women affected by both HIV and CVD had 93 DEGs, only six of which were shared by the HIV alone DEG signal. CVD alone was associated only with upregulated CDK18, which was also identified as a DEG in the HIV + CVD + group. Conclusion: Concurrent HIV and CVD (HIV + CVD + ) is associated with altered gene expression in NCMs relative to HIV - CVD - , generating responses that involve interleukins (IL32, IL4R), immune checkpoint inhibition (LAG3), chemokines (CCL4, CCL5) and lipid homeostasis (ABCD2).

Introduction: Cardiovascular disease is a major contributor to morbidity and mortality among women living with HIV (WLWH). We previously found HIV infection to be associated with carotid artery plaque, a marker of subclinical atherosclerosis. Plaque morphology and composition may predict plaque rupture and cardiovascular disease events. We characterized the association of HIV-related factors with carotid plaque echomorphology in the WIHS. Methods: Using B-mode ultrasound, we characterized plaque (focal intima-media thickness >1.5 mm) at 6 locations in the right carotid artery in 1,722 participants (1,230 HIV+, 492 HIV-) of the WIHS, a cohort study of women with or at risk for HIV at 6 US sites. Plaque echomorphologic features included relative echogenicity (>50% of plaque is echolucent vs >50% of plaque is echogenic) and surface morphology (smooth vs irregular, i.e., height variations along contour of plaque). We used multinomial logistic regression to assess the odds of each feature vs no plaque comparing HIV+ and HIV- women, adjusting for demographic (e.g., age, race/ethnicity, socioeconomic status), behavioral (e.g., drug/alcohol use, smoking, HCV infection, smoking), cardiometabolic (e.g., systolic blood pressure, BMI, lipids, diabetes) and HIV-related risk factors (e.g., antiretroviral therapy use, current CD4+ T-cell count, AIDS). We further stratified WLWH by CD4+ count ( Results: Among 1,722 women (median age 40, IQR 33-46, 59% black, 29% Hispanic, 71% HIV+), 160 (9%) had at least one carotid plaque (128 HIV+, 32 HIV-). In unadjusted analyses, WLWH had more echolucent plaque (5.3% vs 2.6%, p=0.02) and plaques with smooth surface (2.7% vs 0.6%, p=0.005) than HIV-negative women. After covariate adjustment, HIV serostatus remained significantly associated with smooth plaque (odds ratio [OR] 3.45, 95% CI 1.12-10.62) but not with echolucent plaque (OR 1.60, 95% CI 0.84-3.05). Stratified by HIV viremia, WLWH with unsuppressed HIV viremia had significantly more smooth plaque (OR 3.34, 95% CI 1.26-8.87) than HIV- women, whereas suppressed WLWH did not (OR 1.79, 95% CI 0.55-5.83). In a dose-response manner, lower CD4+ count among WLWH was associated with smooth plaque (e.g., OR for Conclusions: Unsuppressed viremia and low CD4+ count, which are markers of suboptimal HIV care, were associated with certain echomorphologic features of carotid plaque. Further work should assess whether these features differentially lead to cardiovascular morbidity and mortality in WLWH.

Diabetes mellitus (DM) is associated with expansion of proinflammatory lymphocyte subsets. We investigated the relationship of total white blood cell (WBC) count and lymphocyte subsets with incident DM in the Women's Interagency HIV Study (WIHS). Higher CD4 and CD8 T cell counts, lymphocyte count, and total WBC count were associated with incident DM among both women with and without HIV, although the association of CD8 was not statistically significant among women without HIV.

AimsTo test whether human immunodeficiency virus (HIV) infection and subclinical cardiovascular disease (sCVD) are associated with expression of CXCR4 and other surface markers on classical, intermediate, and non-classical monocytes in women.Methods and resultssCVD was defined as presence of atherosclerotic lesions in the carotid artery in 92 participants of the Women’s Interagency HIV Study (WIHS). Participants were stratified into four sets (n = 23 each) by HIV and sCVD status (HIV−/sCVD−, HIV−/sCVD+, HIV+/sCVD−, and HIV+/sCVD+) matched by age, race/ethnicity, and smoking status. Three subsets of monocytes were determined from archived peripheral blood mononuclear cells. Flow cytometry was used to count and phenotype surface markers. We tested for differences by HIV and sCVD status accounting for multiple comparisons. We found no differences in monocyte subset size among the four groups. Expression of seven surface markers differed significantly across the three monocyte subsets. CXCR4 expression [median fluorescence intensity (MFI)] in non-classical monocytes was highest among HIV−/CVD− [628, interquartile range (IQR) (295–1389)], followed by HIV+/CVD− [486, IQR (248–699)], HIV−/CVD+ (398, IQR (89–901)), and lowest in HIV+/CVD+ women [226, IQR (73–519)), P = 0.006 in ANOVA. After accounting for multiple comparison (Tukey) the difference between HIV−/CVD− vs. HIV+/CVD+ remained significant with P = 0.005 (HIV−/CVD− vs. HIV+/CVD− P = 0.04, HIV−/CVD− vs. HIV−/CVD+ P = 0.06, HIV+/CVD+ vs. HIV+/CVD− P = 0.88, HIV+/CVD+ vs. HIV−/CVD+ P = 0.81, HIV+/CVD− vs. HIV−/CVD+, P = 0.99). All pairwise comparisons with HIV−/CVD− were individually significant (P = 0.050 vs. HIV−/CVD+, P = 0.028 vs. HIV+/CVD−, P = 0.009 vs. HIV+/CVD+). CXCR4 expression on non-classical monocytes was significantly higher in CVD− (501.5, IQR (249.5–887.3)) vs. CVD+ (297, IQR (81.75–626.8) individuals (P = 0.028, n = 46 per group). CXCR4 expression on non-classical monocytes significantly correlated with cardiovascular and HIV−related risk factors including systolic blood pressure, platelet and T cell counts along with duration of antiretroviral therapy (P ConclusionCXCR4 expression in non-classical monocytes was significantly lower among women with both HIV infection and sCVD, suggesting a potential atheroprotective role of CXCR4 in non-classical monocytes.