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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.

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 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 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.

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.

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.

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.

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.

BACKGROUND Vascular stiffness is associated with aging and cognitive impairment in older populations without HIV. HIV has been linked to increased vascular stiffness. We examined whether vascular stiffness relates to cognitive decline at younger ages in women with or at risk for HIV. METHODS We evaluated the association of carotid artery stiffness with decline in neuropsychological test performance among participants in the Women's Interagency HIV Study and assessed whether HIV modified the association. Baseline carotid stiffness, defined by the distensibility index, was determined at a single visit using carotid artery ultrasound. Longitudinal neuropsychological testing from 2004-2016 included Trail Making Tests A and B and the Symbol Digit Modalities Test. Relationships were assessed with linear mixed-effect models adjusted for demographic, behavioral, cardiometabolic, and neuropsychological factors. RESULTS Among 1662 women (1192 [72%] HIV+), median baseline age was 41 years (interquartile range 34-47), with 60% non-Hispanic black and 28% Hispanic. Lower baseline distensibility (greater carotid stiffness) was associated with greater decline in neuropsychological test scores over 10-year follow-up as measured by Symbol Digit Modalities Test (adjusted β = -0.06 per SD, P < 0.001), Trail Making Test A (β = -0.08 per SD; P < 0.001), and Trail Making Test B (β = -0.08 per SD; P < 0.001). Changes in cognitive function did not differ by HIV serostatus, or HIV-related factors. CONCLUSIONS Higher carotid stiffness was independently associated with faster decline in executive functioning, information processing, and psychomotor speed even in mostly middle-aged minority women and regardless of HIV serostatus. Our study highlights the need for cardiovascular risk factor modification to prevent premature cognitive deterioration in this at-risk population.

We examined associations of 5 plasma choline metabolites with carotid plaque among 520 HIV-infected and 217 HIV-uninfected participants (112 incident plaque cases) over 7 years. After multivariable adjustment, higher gut microbiota-related metabolite trimethylamine-N-oxide (TMAO) was associated with an increased risk of carotid plaque in HIV-infected participants (risk ratio = 1.25 per standard deviation increment; 95% confidence interval, 1.05-1.50; P = .01). TMAO was positively correlated with biomarkers of monocyte activation and inflammation (sCD14, sCD163). Further adjustment for these biomarkers attenuated the association between TMAO and carotid plaque (P = .08). Among HIV-infected individuals, plasma TMAO was associated with carotid atherosclerosis progression, partially through immune activation and inflammation.

Individuals with a negative HIV test before a positive one (seroconverters) may represent missed opportunities for prevention. To inform HIV prevention strategies, we aimed to characterize patients who seroconverted despite accessing care. We identified patients at a large, urban healthcare system who seroconverted between 2009 and 2014. Demographics, visits, and HIV-related variables were extracted from the medical records. We performed descriptive statistics, assessed for trends, and tested for associations according to sex. 220 seroconverters were identified: 45% were female, 87% were non-Hispanic Black or Hispanic, and median number of negative tests prior to diagnosis was 2 (IQR 1–3). Overall, 49% reported heterosexual contact as their risk factor and the proportion with heterosexual risk increased over time (24% in 2009 vs. 56% in 2014, p = 0.03). Compared to men, women were older at the time of diagnosis (35 vs. 26 years old, p < 0.01), had more visits between their latest negative and positive HIV test (4 vs. 2, p < 0.01), and were more likely to be diagnosed in the context of screening (64% vs. 56%, p = 0.05). We identified a population that became HIV-infected despite multiple healthcare encounters and undergoing HIV testing multiple times. Patients were mostly heterosexual and almost half were female. To avoid missed opportunities for those already accessing care, HIV prevention efforts should include strategies tailored to individuals with less frequently recognized risk profiles.

BACKGROUND: Data on associations between abdominal fat depot mass and subclinical atherosclerosis are limited, especially in women with HIV. METHODS: We assessed cross-sectional associations of dual X-ray absorptiometry scan-derived estimates of visceral adipose tissue (VAT) and abdominal subcutaneous adipose tissue (SAT) with 3 measures of subclinical carotid artery atherosclerosis-- carotid artery stiffness (Young’s modulus of elasticity), presence of carotid artery lesions, and carotid artery intima-media thickness (cIMT)-- in a subsample of participants in the Women’s Interagency HIV Study. Statistical models adjusted for demographic variables, HIV serostatus, behavioral variables, and cardiovascular risk factors. RESULTS: There were 244 women with and 99 without HIV infection (median age 42, 62% black). VAT mass (but not SAT) was associated with greater carotid artery stiffness in a fully adjusted linear regression model, including adjustment for SAT (β = 11.3 log 10(3) N*M(−2) per kg VAT, 95% confidence interval [1.0, 21.7]). Greater SAT mass was associated with lower odds of having a carotid artery lesion in a fully adjusted model, including adjustment for VAT (adjusted odds ratio, 0.49 per kg of SAT [0.25, 0.94]). Neither VAT nor SAT was associated with cIMT. The VAT/SAT ratio was not statistically associated with any of the outcomes after covariate adjustment. CONCLUSIONS: In our cross-sectional study of women, the majority of whom had HIV, greater VAT mass was associated with increased carotid artery stiffness whereas greater SAT mass was associated with a reduced odds of prevalent carotid artery lesions.

HIV-infected undocumented immigrants face unique barriers to care yet little is known about their clinical outcomes. We performed a retrospective cohort study of HIV-infected adults in clinical care from 2006 to 2014 at a large academic medical center in a setting where medical insurance is available to HIV-infected undocumented immigrants. Undocumented status was assessed based on Social Security number and insurance status and verified through medical chart review. Using Poisson regression models, we compared undocumented and documented patients with respect to retention in care (≥2 HIV-related laboratory tests ≥90 days apart), antiretroviral therapy (ART) prescription (≥3 active antiretroviral agents prescribed in a year), and viral suppression (HIV RNA

Background People living with HIV have an increased risk of left ventricular diastolic dysfunction ( LVDD ) and heart failure. HIV ‐associated LVDD may reflect both cardiomyocyte and systemic metabolic derangements, but the underlying pathways remain unclear. Methods and Results To explore such pathways, we conducted a pilot study in the Bronx and Brooklyn sites of the WIHS (Women's Interagency HIV Study) who participated in concurrent, but separate, metabolomics and echocardiographic ancillary studies. Liquid chromatography tandem mass spectrometry–based metabolomic profiling was performed on plasma samples from 125 HIV‐infected (43 with LVDD) and 35 HIV‐uninfected women (9 with LVDD). Partial least squares discriminant analysis identified polar metabolites and lipids in the glycerophospholipid‐metabolism and fatty‐acid‐oxidation pathways associated with LVDD . After multivariable adjustment, LVDD was significantly associated with higher concentrations of diacylglycerol 30:0 (odds ratio [ OR ], 1.60, 95% CI [1.01–2.55]); triacylglycerols 46:0 ( OR 1.60 [1.04–2.48]), 48:0 ( OR 1.63 [1.04–2.54]), 48:1 ( OR 1.62 [1.01–2.60]), and 50:0 ( OR 1.61 [1.02–2.53]); acylcarnitine C7 ( OR 1.88 [1.21–2.92]), C9 ( OR 1.99 [1.27–3.13]), and C16 ( OR 1.80 [1.13–2.87]); as well as lower concentrations of phosphocholine ( OR 0.59 [0.38–0.91]). There was no evidence of effect modification of these relationships by HIV status. Conclusions In this pilot study, women with or at risk of HIV with LVDD showed alterations in plasma metabolites in the glycerophospholipid‐metabolism and fatty‐acid‐oxidation pathways. Although these findings require replication, they suggest that improved understanding of metabolic perturbations and their potential modification could offer new approaches to prevent cardiac dysfunction in this high‐risk group.

Introduction: Population health surveys inform and demonstrate the impact of public health policies. However, the performance of such surveys in specific groups of interest (e.g., Hispanics/Latinos in a neighborhood of New York City) is rarely studied. Method: We compared measures for obesity, hypertension, diabetes, and current smoking based on the New York City Community Health Survey (CHS, a telephone survey of New York City adults) with the Hispanic Community Health Survey/Study of Latinos (HCHS/SOL), an in-person survey of Hispanic/Latino adults in four communities in the United States (2008-2011), including the Bronx. CHS data were limited to Hispanic/Latinos living in the HCHS/SOL Bronx catchment area. Results: Compared with CHS, HCHS/SOL estimated higher prevalence of obesity (in HCHS/SOL, PHCHS/SOL = 45.0% vs. in CHS, PCHS = 30.6%, p < .01) and current smoking (PHCHS/SOL = 21.2% vs. PCHS = 16.2%, p < .01) but similar for hypertension (PHCHS/SOL = 33.1% vs. PCHS = 33.8%, p > .05) and diabetes (PHCHS/SOL = 15.2% vs. PCHS = 15.7%, p > .05). Stratified estimates (by age, sex, education, and Hispanic/Latino heritage) followed similar trends. Conclusion: Our study emphasizes the importance of assessing potential bias in population-based surveys of Hispanics/Latinos and other populations of interest and highlights the complex nature of measuring health outcomes via population-based surveys.

Background Expression of tissue factor (TF) on the surface of activated monocytes may trigger thrombosis, leading to clotting risk, inflammation, and atherosclerosis. TF-positive microparticles (MP-TF) represent a functionally active form of TF that may be promulgated by long-term HIV infection. We hypothesized that greater MP-TF activity is associated with carotid artery plaque in HIV+ women. Setting In a case-control study nested within the Women's Interagency HIV Study (WIHS), eligible HIV+ participants underwent B-mode carotid artery ultrasound at 2 study visits occurring 7 years apart. Cases were defined by the presence of at least 1 carotid artery plaque assessed at either visit. Cases were matched 1:2 to controls who were found not to have carotid artery plaques. Methods Conditional logistic regression estimated the association of MP-TF activity with the presence of carotid artery plaque, adjusting for demographic and behavioral characteristics, HIV-related factors, cardiometabolic risk factors, and serum inflammation biomarkers (high-sensitivity C-reactive protein, IL-6, sCD14, sCD163, Gal-3, and Gal-3BP). Results Elevated MP-TF activity (>0.537 pg/mL) was found to be significantly associated with greater odds of plaque (adjusted odds ratio 3.86, 95% confidence interval: 1.06 to 14.07, P = 0.04). The association was attenuated after further adjustment for IL-6 but was unaffected by adjustment for other biomarkers including those denoting monocyte activation. Conclusions Our findings suggest a link among HIV infection, innate immune system perturbation, coagulation, and atherosclerosis.

PURPOSE: To investigate the association between undocumented immigration status and anxiety, depression and use of anxiolytic or antidepressant medications in the Hispanic Community Health Study/Study of Latinos. METHODS: Cross-sectional analysis of data collected between 2014–2017. Participants were categorized as US-born citizens, naturalized citizens, documented non-citizens, or undocumented non-citizens. We calculated prevalence and prevalence ratios (PRs) for anxiety, depression and use of anxiolytic or antidepressant medication, by immigration status. RESULTS: Of 9,257 participants, 1403 (15%) were undocumented non-citizens, 2872 (31%) were documented non-citizens, 3766 (41%) were naturalized citizens, and 1216 (13%) were US-born citizens. Prevalence of anxiety was lower among undocumented compared to documented noncitizens (9 vs 15%, p

Objective We developed and validated the first-ever sleep apnea (SA) risk calculator in a large population-based cohort of Hispanic/Latino subjects. Methods Cross-sectional data on adults from the Hispanic Community Health Study/Study of Latinos (2008-2011) were analyzed. Subjective and objective sleep measurements were obtained. Clinically significant SA was defined as an apnea-hypopnea index ≥ 15 events per hour. Using logistic regression, four prediction models were created: three sex-specific models (female-only, male-only, and a sex × covariate interaction model to allow differential predictor effects), and one overall model with sex included as a main effect only. Models underwent 10-fold cross-validation and were assessed by using the C statistic. SA and its predictive variables; a total of 17 variables were considered. Results A total of 12,158 participants had complete sleep data available; 7,363 (61%) were women. The population-weighted prevalence of SA (apnea-hypopnea index ≥ 15 events per hour) was 6.1% in female subjects and 13.5% in male subjects. Male-only (C statistic, 0.808) and female-only (C statistic, 0.836) prediction models had the same predictor variables (ie, age, BMI, self-reported snoring). The sex-interaction model (C statistic, 0.836) contained sex, age, age × sex, BMI, BMI × sex, and self-reported snoring. The final overall model (C statistic, 0.832) contained age, BMI, snoring, and sex. We developed two websites for our SA risk calculator: one in English ( https://www.montefiore.org/sleepapneariskcalc.html ) and another in Spanish ( http://www.montefiore.org/sleepapneariskcalc-es.html ). Conclusions We created an internally validated, highly discriminating, well-calibrated, and parsimonious prediction model for SA. Contrary to the study hypothesis, the variables did not have different predictive magnitudes in male and female subjects.

Background Age and human immunodeficiency virus (HIV) treatment may affect the association of HIV infection with atherosclerosis. Methods We used identical carotid artery B-mode ultrasonographic methods in 5 cohorts participating in the National Heart, Lung, and Blood Institute HIV-CVD Collaborative to measure intima-media thickness of the right far wall of the common carotid artery (CCA-IMT) and carotid artery bifurcation (BIF-IMT) between 2010 and 2013. Participants aged 6-75 years were either HIV infected or uninfected. Linear regression assessed associations of CCA-IMT and BIF-IMT with HIV infection and cardiovascular disease risk factors, within age and HIV treatment groups. Adjustment variables included sex, race/ethnicity, smoking, height, weight, and use of antihypertensive and lipid-lowering drugs. Results We studied 867 HIV-infected and 338 HIV-uninfected male and 696 HIV-infected and 246 HIV-uninfected female participants. Among both middle-aged (30-49 years) and older adults (50-75 years), HIV-infected participants had CCA-IMT and BIF-IMT values that were similar to or lower than those in HIV-uninfected participants. In contrast, among those aged 6-29 years, HIV infection was associated with higher CCA-IMT and BIF-IMT values. Among HIV-infected participants, associations of higher systolic blood pressure and lower high-density lipoprotein cholesterol with Carotid artery intima-media thickness strengthened with age. Conclusions The effects of HIV on carotid artery structure may differ across the lifespan, with traditional determinants of cardiovascular disease burden playing a larger role and HIV playing a lesser role in older adults than in young adults and children.

Background: Ceramides have been implicated in the pathophysiology of HIV infection and cardiovascular disease. However, no study, to our knowledge, has evaluated circulating ceramide levels in association with subclinical cardiovascular disease risk among HIV-infected individuals. Methods: Plasma levels of 4 ceramide species (C16:0, C22:0, C24:0, and C24:1) were measured among 398 women (73% HIV+) and 339 men (68% HIV+) without carotid artery plaques at baseline from the Women’s Interagency HIV Study and the Multicenter AIDS Cohort Study. We examined associations between baseline plasma ceramides and risk of carotid artery plaque formation, assessed by repeated B-mode carotid artery ultrasound imaging over a median 7-year follow-up. Results: Plasma levels of C16:0, C22:0, and C24:1 ceramides were significantly higher in HIV-infected individuals compared with those without HIV infection (all P P r =0.70–0.94; all P r =0.42–0.58; all P r =0.24–0.42; all P r =0.30 between C16:0 ceramide and soluble CD14; P + T-cell activation. A total of 112 participants developed carotid artery plaques over 7 years, and higher levels of C16:0 and C24:1 ceramides were significantly associated with increased risk of carotid artery plaques (relative risk [95% CI]=1.55 [1.29, 1.86] and 1.51 [1.26, 1.82] per standard deviation increment, respectively; both P Conclusions: In 2 HIV cohorts, elevated plasma levels of C16:0 and C24:1 ceramides, correlating with immune activation and inflammation, were associated with antiretroviral therapy use and progression of carotid artery atherosclerosis.

Background Prior studies suggest that transgender women (TW) with human immunodeficiency virus (HIV) are less likely to be virally suppressed than cisgender women (CW) and cisgender men (CM). However, prior data are limited by small sample sizes and cross-sectional designs. We sought to characterize the HIV care continuum comparing TW to CW and CM in the United States and Canada. Methods We analyzed annual HIV care continuum outcomes by gender status from January 2001 through December 2015 among adults (aged ≥18 years) in 15 clinical cohorts. Outcomes were retention in care and viral suppression. Results The study population included TW (n = 396), CW (n = 14 094), and CM (n = 101 667). TW had lower proportions retained in care than CW and CM (P < .01). Estimates of retention in care were consistently lower in TW, with little change over time within each group. TW and CW had similar proportions virally suppressed over time (TW, 36% in 2001 and 80% in 2015; CW, 35% in 2001 and 83% in 2015) and were lower than CM (41% in 2001 and 87% in 2015). These differences did not reach statistical significance after adjusting for age, race, HIV risk group, and cohort. Conclusions TW experience challenges with retention in HIV care. However, TW who are engaged in care achieve viral suppression that is comparable to that of CW and CM of similar age, race, and HIV risk group. Further research is needed to understand care engagement disparities.

Background The risk of mortgage foreclosure disproportionately burdens Hispanic/Latino populations perpetuating racial disparities in health. In this study, we examined the relationship between area-level mortgage foreclosure risk, homeownership, and the prevalence of cardiovascular disease risk factors among participants of the Hispanic Community Health Study/Study of Latinos (HCHS/SOL). Methods HCHS/SOL participants were age 18–74 years when recruited from four U.S. metropolitan areas. Mortgage foreclosure risk was obtained from the U.S. Department of Housing and Urban Development. Homeownership, sociodemographic factors, and cardiovascular disease risk factors were measured at baseline interview between 2008 and 2011. There were 13,856 individuals contributing to the analysis (median age 39 years old, 53% female). Results Renters in high foreclosure risk areas had a higher prevalence of hypertension and hypercholesterolemia but no association with smoking status compared to renters in low foreclosure risk areas. Renters were more likely to smoke cigarettes than homeowners. Conclusion Among US Hispanic/Latinos in urban cities, area foreclosure and homeownership have implications for risk of cardiovascular disease.

Background: People living with HIV are at risk of increased myocardial infarction (MI). Cumulative HIV viral load (VL) has been proposed as a better measure of HIV inflammation than other measures of VL, like baseline VL, but its associations with MI are not known. Methods: The multisite Centers for AIDS Research Network of Integrated Clinical Systems (CNICS) cohort includes clinical data and centrally adjudicated MI with distinction between atheroembolic MI (type 1) and MI related to supply-demand mismatch (type 2). We examined CNICS participants who were not on antiretroviral therapy (ART) at enrollment. Cumulative VL (copy-days of virus) from 6 months after enrollment was estimated with a time-weighted sum using the trapezoidal rule. We modeled associations of cumulative and baseline VL with MI by type using marginal structural Cox models. We contrasted the 75% percentile of the VL distribution with the 25% percentile. Results: Among 11,324 participants, 218 MIs occurred between 1996 and 2016. Higher cumulative VL was associated with risk of all MI (hazard ratio [HR] = 1.72; 95% confidence interval [CI] = 1.26, 2.36), type 1 MI (HR = 1.23; 95% CI = 0.78, 1.96), and type 2 MI (HR = 2.52; 95% CI = 1.74, 3.66). While off ART, cumulative VL had a stronger association with type 1 MI (HR = 2.13; 95% CI = 1.15, 3.94) than type 2 MI (HR = 1.25; 95% CI = 0.70, 2.25). Baseline VL was associated with all MI (HR = 1.60; 95% CI = 1.28, 2.01), type 1 MI (HR = 1.73; 95% CI = 1.26, 2.38), and type 2 MI (HR = 1.51; 95% CI = 1.10, 2.08). Conclusions: Higher cumulative and baseline VL is associated with all MI, with a particularly strong association between cumulative VL and type 2 MI.

Background HIV is associated with elevated risk of heart failure ( HF ). Despite poor agreement between automated, administrative code–based HF definitions and physician‐adjudicated HF , no studies have evaluated incident adjudicated HF for people living with HIV ( PLWH ). Methods and Results We analyzed PLWH and uninfected controls receiving care in an urban medical system from January 1, 2000, to July 12, 2016. Physicians reviewed data from medical records to adjudicate HF diagnoses. We used multivariable‐adjusted Cox models to analyze incident HF for PLWH versus controls and HIV ‐related factors associated with incident HF . We also analyzed the performance of automated versus physician‐adjudicated HF definitions. Incident adjudicated HF occurred in 97 of 4640 PLWH (2.1%; mean: 6.8 years to HF ) and 55 of 4250 controls (1.3%; mean: 6.7 years to HF ; multivariable‐adjusted hazard ratio: 2.10; 95% confidence interval, 1.38–3.21). Among PLWH , higher HIV viral load ( hazard ratio per log 10 higher time‐updated viral load: 1.22; 95% confidence interval, 1.11–1.33) was associated with greater HF risk and higher CD 4+ T cell count was associated with lower HF risk ( hazard ratio per 100 cells/mm 3 higher time‐updated CD 4 count: 0.80; 95% confidence interval, 0.69–0.92). In exploratory analyses, the most accurate automated HF definitions had sensitivities of 67% to 75% and positive predictive values of 54% to 60%. Conclusions In a cohort with rigorous HF adjudication, PLWH had greater risks of HF than uninfected people after adjustment for demographics and cardiovascular risk factors. Higher HIV viral load and lower CD 4+ T cell count were associated with higher HF risk among PLWH . Automated methods of HF ascertainment exhibited poor accuracy for PLWH and uninfected people.

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

Objective The aim of this study was to determine the associations between visceral adipose tissue (VAT) and abdominal subcutaneous adipose tissue (SAT) mass with homeostatic model assessment-insulin resistance (HOMA-IR) and incidence of diabetes mellitus in women with and without HIV infection. Design Cross-sectional design for associations between abdominal fat and HOMA-IR; longitudinal design for associations between abdominal fat and incident diabetes. Methods We assessed associations between dual X-ray absorptiometry scan-derived VAT and SAT with HOMA-IR in a subsample from the Women's Interagency HIV Study (n = 226 with and n = 100 without HIV) using linear regression. We evaluated associations of VAT, SAT and HOMA-IR with incident diabetes mellitus using Cox proportional hazards models. Results VAT mass was positively associated with log HOMA-IR in fully adjusted linear regression models stratified by HIV serostatus, including adjustment for SAT. During median follow-up of 10.6 years, incidence of diabetes was 1.63 [95% confidence interval (95% CI) 1.15-2.31] and 1.32 [95% CI 0.77-2.28] cases per 100 person-years in women with and without HIV (P = 0.52). In a fully adjusted model, baseline VAT (hazard ratio 2.64 per kg; 95% CI 1.14-6.12; P = 0.023) and SAT (hazard ratio 1.34 per kg; 95% CI 0.73-2.45; P = 0.35) were associated with incident diabetes, but the latter was not statistically significant. Conclusion VAT mass was independently associated with HOMA-IR in women with and without HIV and was independently associated with future development of diabetes.

While mortality rates related to cardiovascular disease (CVD) have decreased over time among adults with HIV, excess risk of CVD in the HIV-infected population may persist despite highly active antiretroviral therapy (HAART) treatment and aggressive CVD risk factor control. Beyond atherosclerotic CVD, recent studies suggest that HIV infection may be associated with left ventricular systolic and diastolic function, interstitial myocardial fibrosis, and increased cardiac fat infiltration. Thus, with the increasing average age of the HIV-infected population, heart failure and arrhythmic disorders may soon rival coronary artery disease as the most prevalent forms of CVD. Finally, the question of whether HIV infection should be considered in clinical risk stratification has never been resolved, and this question has assumed new importance with recent changes to lipid treatment guidelines for prevention of CVD.

Objective HIV is a cardiovascular disease (CVD) risk factor. However, CVD risk is often underestimated in HIV-infected women. C-reactive protein (CRP) may improve CVD prediction in this population. We examined the association of baseline plasma CRP with subclinical CVD in women with and without HIV. Design Retrospective cohort study. Methods A total of 572 HIV-infected and 211 HIV-uninfected women enrolled in the Women's Interagency HIV Study underwent serial high-resolution B-mode carotid artery ultrasonography between 2004 and 2013 to assess carotid intima-media thickness (CIMT) and focal carotid artery plaques. We used multivariable linear and logistic regression models to assess the association of baseline high (≥3 mg/l) high-sensitivity (hs) CRP with baseline CIMT and focal plaques, and used multivariable linear and Poisson regression models for the associations of high hsCRP with CIMT change and focal plaque progression. We stratified our analyses by HIV status. Results Median (interquartile range) hsCRP was 2.2 mg/l (0.8-5.3) in HIV-infected, and 3.2 mg/l (0.9-7.7) in HIV-uninfected, women (P = 0.005). There was no statistically significant association of hsCRP with baseline CIMT [adjusted mean difference -3.5 μm (95% confidence interval:-19.0 to 12.1)] or focal plaques [adjusted odds ratio: 1.31 (0.67-2.67)], and no statistically significant association of hsCRP with CIMT change [adjusted mean difference 11.4 μm (-2.3 to 25.1)]. However, hsCRP at least 3 mg/l was positively associated with focal plaque progression in HIV-uninfected [adjusted rate ratio: 5.97 (1.46-24.43)], but not in HIV-infected [adjusted rate ratio: 0.81 (0.47-1.42)] women (P = 0.042 for interaction). Conclusion In our cohort of women with similar CVD risk factors, higher baseline hsCRP is positively associated with carotid plaque progression in HIV-uninfected, but not HIV-infected, women, suggesting that subclinical CVD pathogenesis may be different HIV-infected women.

BACKGROUND: It is unknown whether disrupted tryptophan catabolism is associated with cardiovascular disease (CVD) in human immunodeficiency virus (HIV)–infected individuals. METHODS: Plasma tryptophan and kynurenic acid were measured in 737 women and men (520 HIV+, 217 HIV−) from the Women’s Interagency HIV Study and the Multicenter AIDS Cohort Study. Repeated B-mode carotid artery ultrasound imaging was obtained from 2004 through 2013. We examined associations of baseline tryptophan, kynurenic acid, and kynurenic acid-to-tryptophan (KYNA/TRP) ratio, with risk of carotid plaque. RESULTS: After a 7-year follow-up, 112 participants developed carotid plaque. Compared to those without HIV infection, HIV-infected participants had lower tryptophan (P < .001), higher KYNA/TRP (P = .01), and similar kynurenic acid levels (P = .51). Tryptophan, kynurenic acid, and KYNA/TRP were correlated with T-cell activation (CD38+HLA-DR+) and immune activation markers (serum sCD14, galectin-3) but had few correlations with interleukin-6, C-reactive protein, or CVD risk factors (blood pressure, lipids). Adjusted for demographic and behavioral factors, each standard deviation (SD) increment in tryptophan was associated with a 29% (95% confidence interval [CI], 17%–38%) decreased risk of carotid plaque (P < .001), while each SD increment in kynurenic acid (P = .02) and KYNA/TRP (P < .001) was associated with a 34% (6%–69%) and a 47% (26%–73%) increased risk of carotid plaque, respectively. After further adjustment for CVD risk factors and immune activation markers, these associations were attenuated but remained significant. CONCLUSIONS: Plasma tryptophan-kynurenine metabolites are altered in HIV infection and associated with progression of carotid artery atherosclerosis.

Migrants living in high-income countries are disproportionately affected by HIV infection and frequently have characteristics associated with poor HIV clinical outcomes. HIV epidemiology among migrants is influenced by changes in migration patterns and variations in transmission risk behaviors. Here we review the recently published literature on known HIV outcomes among migrants from low-income and middle-income countries living in high-income countries.High proportions of migrants acquire HIV after migration, and this group frequently presents to care late. Once established in care, migrants are often more likely to experience worse HIV treatment outcomes compared with native populations. Multiple individual and structural factors influence HIV diagnosis and treatment outcomes among migrants, including disruption of social networks, increased sexual risk behaviors, communication barriers, limited access to care, and stigma. Few studies have examined interventions targeted at improving HIV outcomes among migrants.Stigma and limited access to care appear to be primary drivers of poor HIV outcomes among migrants in high-income countries. Addressing these disparities is limited by difficulties in identifying and monitoring this population as well as a lack of evidence regarding appropriate interventions for migrants living with HIV. Improving outcomes for this group requires interventions that are specifically targeted at this marginalized and growing population.

BACKGROUND: Prevention of mother-to-child transmission of human immunodeficiency virus (HIV) with antiretroviral therapy (ART) has been highly successful. However, HIV-exposed uninfected (HIV-EU) infants might be at increased risk for low birth weight and/or preterm birth. We compared the birth weights and gestational ages of HIV-EU infants to those of HIV-unexposed control infants in Bronx, New York, an epicenter of the HIV epidemic in the United States. METHODS: This study was performed with a retrospective cohort of HIV-EU infants born at Montefiore Medical Center between 2008 and 2012 and HIV-unexposed control infants. Each HIV-EU infant was matched according to year of birth with 5 HIV-unexposed controls from the New York City Department of Health and Mental Hygiene birth certificate database. We used regression models to assess the association between HIV exposure and birth weight while controlling for potential confounders. A secondary analysis was performed to determine the association of maternal protease inhibitor–based ART use and birth weight among HIV-EU infants. RESULTS: We included 155 HIV-EU infants born between 2008 and 2012 (51% female, 61% black, 32% Hispanic) and 775 HIV-unexposed infants. The mean (± standard deviation) unadjusted birth weights were 2971 ± 616 g (HIV-EU infants) and 3163 ± 644 g (HIV-unexposed infants) (P < .01). Multivariable regression revealed significantly lower birth weight for the HIV-EU infants (difference, −101.5 g [95% confidence interval, −181.4 to −21.6]). We found no difference in mean birth weight or gestational age with maternal protease inhibitor–based ART use when compared to the use of other regimens. CONCLUSIONS: We found significantly lower birth weight among HIV-EU infants. Long-term prospective studies are necessary to determine the implications of this finding on infant growth and development.

Cardiovascular disease (CVD) is a major comorbidity among HIV-infected individuals. Common carotid artery intima-media thickness (cCIMT) is a valid and reliable subclinical measure of atherosclerosis and is known to predict CVD. We performed genome-wide association (GWA) and admixture analysis among 682 HIV-positive and 288 HIV-negative Black, non-Hispanic women from the Women’s Interagency HIV study (WIHS) cohort using a combined and stratified analysis approach. We found some suggestive associations but none of the SNPs reached genome-wide statistical significance in our GWAS analysis. The top GWAS SNPs were rs2280828 in the region intergenic to mediator complex subunit 30 and exostosin glycosyltransferase 1 (MED30 | EXT1) among all women, rs2907092 in the catenin delta 2 (CTNND2) gene among HIV-positive women, and rs7529733 in the region intergenic to family with sequence similarity 5, member C and regulator of G-protein signaling 18 (FAM5C | RGS18) genes among HIV-negative women. The most significant local European ancestry associations were in the region intergenic to the zinc finger and SCAN domain containing 5D gene and NADH: ubiquinone oxidoreductase complex assembly factor 1 (ZSCAN5D | NDUF1) pseudogene on chromosome 19 among all women, in the region intergenic to vomeronasal 1 receptor 6 pseudogene and zinc finger protein 845 (VN1R6P | ZNF845) gene on chromosome 19 among HIV-positive women, and in the region intergenic to the SEC23-interacting protein and phosphatidic acid phosphatase type 2 domain containing 1A (SEC23IP | PPAPDC1A) genes located on chromosome 10 among HIV-negative women. A number of previously identified SNP associations with cCIMT were also observed and included rs2572204 in the ryanodine receptor 3 (RYR3) and an admixture region in the secretion-regulating guanine nucleotide exchange factor (SERGEF) gene. We report several SNPs and gene regions in the GWAS and admixture analysis, some of which are common across HIV-positive and HIV-negative women as demonstrated using meta-analysis, and also across the two analytic approaches (i.e., GWA and admixture). These findings suggest that local European ancestry plays an important role in genetic associations of cCIMT among black women from WIHS along with other environmental factors that are related to CVD and may also be triggered by HIV. These findings warrant confirmation in independent samples.