Search

Abstract People living with HIV (PLWH) experience increased vulnerability to premature aging and inflammation-associated comorbidities, even when HIV replication is suppressed by antiretroviral therapy (ART). However, the factors associated with this vulnerability remain uncertain. In the general population, alterations in the N-glycans on IgGs trigger inflammation and precede the onset of aging-associated diseases. Here, we investigate the IgG N-glycans in cross-sectional and longitudinal samples from 1214 women and men, living with and without HIV. PLWH exhibit an accelerated accumulation of pro-aging-associated glycan alterations and heightened expression of senescence-associated glycan-degrading enzymes compared to controls. These alterations correlate with elevated markers of inflammation and the severity of comorbidities, potentially preceding the development of such comorbidities. Mechanistically, HIV-specific antibodies glycoengineered with these alterations exhibit a reduced ability to elicit anti-HIV Fc-mediated immune activities. These findings hold potential for the development of biomarkers and tools to identify and prevent premature aging and comorbidities in PLWH.

Abstract Background Gut dysbiosis has been linked with both HIV infection and diabetes, but its interplay with metabolic and inflammatory responses in diabetes, particularly in the context of HIV infection, remains unclear. Methods We first conducted a cross-sectional association analysis to characterize the gut microbial, circulating metabolite, and immune/inflammatory protein features associated with diabetes in up to 493 women (~ 146 with prevalent diabetes with 69.9% HIV +) of the Women’s Interagency HIV Study. Prospective analyses were then conducted to determine associations of identified metabolites with incident diabetes over 12 years of follow-up in 694 participants (391 women from WIHS and 303 men from the Multicenter AIDS Cohort Study; 166 incident cases were recorded) with and without HIV infection. Mediation analyses were conducted to explore whether gut bacteria–diabetes associations are explained by altered metabolites and proteins. Results Seven gut bacterial genera were identified to be associated with diabetes (FDR-q

Abstract 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. Video Abstract

Abstract 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.

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.

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: 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.

Abstract 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.

Abstract Background Incarceration disproportionately affects people living with HIV/AIDS. When people are released from jail or prison, they face multiple barriers to HIV care, and those who do engage in care may have suboptimal HIV treatment outcomes. A limited number of studies have investigated HIV treatment outcomes among people who have been released from incarceration. Methods We conducted a retrospective cohort study comparing HIV viral load (VL) suppression and retention in care 12 months after entry into care among patients of a post-incarceration Transitions Clinic (TC) and a comparison group who received HIV care in the same community. Of 138 participants, 38 TC patients were matched to 100 non-TC controls based on age, race/ethnicity, gender, and date of HIV care entry. Results There was no significant difference in clinical study outcomes between TC and non-TC patients: 63% vs. 67% (p = 0.67) were retained in care and 54% vs. 63% (p = 0.33) had suppressed VL at 12 months. After adjusting for substance use disorder and viral load suppression at the start of treatment, the odds ratio of TC patients’ 12-month retention was 0.60 (95% CI 0.25–1.49) and VL suppression was 0.44 (95% CI 0.16–1.23) compared with non-TC patients. Conclusions Our findings show HIV care outcomes for patients at a post-incarceration Transitions Clinic that are similar to those of community-based comparison patients. The transitions clinic model, which provides medical, behavioral health, and supportive services to formerly incarcerated people, may be an effective model of care for this population; however, more scholarship is needed to quantify the components most effective in supporting retention in care and viral load suppression.

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.

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 log10 higher time‐updated viral load: 1.22; 95% confidence interval, 1.11–1.33) was associated with greater HF risk and higher CD4+ T cell count was associated with lower HF risk (hazard ratio per 100 cells/mm3 higher time‐updated CD4 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 CD4+ T cell count were associated with higher HF risk among PLWH. Automated methods of HF ascertainment exhibited poor accuracy for PLWH and uninfected people.

Abstract Alfalfa is a high-quality forage legume species that is widely cultivated at high latitudes worldwide. However, a decrease in cold tolerance in early spring seriously affects regrowth and persistence of alfalfa. There has been limited research on the metabolomic changes that occur during de-acclimation. In this study, a liquid chromatography–mass spectrometry system was used to compare the metabolites in two alfalfa cultivars during a simulated overwintering treatment. In four pairwise comparisons, 367 differential metabolites were identified, of which 31 were annotated according to the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. Many of these metabolites were peptides, carbohydrates, and lipids. At the subclass level, 17 major pathways were revealed to be significantly enriched (P

Leymus chinensis steppe is subject to degradation under the combined stresses of climate change and human disturbance. This study aimed to determine the independent and compound effects of precipitation and clipping frequency on the community structure and species temporal stability of L. chinensis steppe. Six treatments were applied in a 9-year field study, comprising three precipitation regimes (precipitation reduced by 50%, R1; unchanged from ambient precipitation, R2; and increased by 50%, R3) and two clipping frequencies (clipping once or twice per year, C1 and C2). We evaluated the soil hydrothermal status, dry matter, importance value and temporal stability of five important species (L. chinensis, Artemisia eriopoda, Cleistogenes squarrosa, Potentilla tanacetifolia, and Stipa krylovii) in the L. chinensis community. The results showed: Change in the soil volumetric water content (±2.4%) altered the competitive capability of L. chinensis relative to its associated species. Drought was beneficial to S. krylovii, wet status was favorable to C. squarrosa and P. tanacetifolia, whereas drought and a wet regime both reduced the importance value and temporal stability of L. chinensis. Erratic precipitation, rather than clipping frequency, decreased the temporal stability of L. chinensis. Net primary productivity and dry matter of L. chinensis were strongly correlated under drought or wet regimes. Restoration of the key species L. chinensis and controlling grazing intensity in severe drought or wet conditions are recommended strategies for sustainable management of L. chinensis steppe.

This study aimed to investigate the impact of storage time on the bacterial community and fermentation profile of silage prepared with alfalfa, whole-plant corn, and their mixture. Fresh alfalfa and whole-plant corn were chopped and combined in fresh weight ratios of 1:0 (alfalfa, control), 0.8:0.2 (M1), 0.6:0.4 (M2), and 0:1 (corn). Three silos of each treatment were analyzed after 30, 60, and 90 d of storage. With storage time, pH, acetic acid, propionic acid, butyric acid, and ammonia nitrogen levels increased in alfalfa silage (p < 0.01), whereas lactic acid level decreased (p < 0.01). Compared to alfalfa silage, M1, M2, and corn silages were better fermented and more stable during storage. The dominant bacteria in M1, M2, and corn silages shifted significantly from L. plantarum, L. buchneri, and L. brevis to L. acetotolerans and L. buchneri during 30 to 60–90 d of storage, and storage time decreased the bacterial diversity of these silages. In conclusion, storage time significantly decreased the fermentation quality of alfalfa silage and remarkably optimized the bacterial community structure of well-fermented M1, M2, and corn silages. Alfalfa should be ensiled with at least 20% whole-plant corn to improve silage fermentation quality and storage stability.

Concerns about inappropriate storage, application rates, and disposal practices of pesticides prompted this case study of Vietnamese farmers' knowledge, attitudes, and practices. 128 small-scale vegetable growers in Lam Dong Province were included in field surveys, questionnaires, and interviews. Farmers reported inappropriate mixing of pesticides and disposal methods. Many also reported ill-timed applications posing potential hazards to the human health and environment. Improved training and monitoring of pesticide residues on foodstuffs and in agricultural soils and community water supplies are needed to ensure safe farmer practices. Community-based training and education, jointly funded by local, national, and international agricultural production and food safety groups, would be a cost-effective method of minimising pesticide applications and improving food safety.

The influence of mixing alfalfa with whole-plant corn in different proportions on the fermentation characteristics and bacterial community of silage was investigated. Alfalfa and whole-plant corn, harvested at dry matter content of 276.47 and 328.43 g/kg fresh weight, accordingly, were chopped to approximately 2 cm and mixed at ratios of 100:0 (C0, control), 80:20 (C20), 60:40 (C40), 40:60 (C60), 20:80 (C80) and 0:100 (C100) on a fresh weight basis, respectively. Silos of each treatment were produced in triplicate and anaerobically fermented in darkness for 100 days at room temperature (20–21 °C). At silo opening, silage fermentation characteristics and bacterial composition and diversity were analyzed. The C0 silage was weakly preserved, evidenced by a low lactic acid concentration and a high value of pH, acetic acid, propionic acid, butyric acid and ammonia nitrogen. With corn proportion in the mixture increasing from 0% to 40%, silage pH, acetic acid, butyric acid and ammonia nitrogen level decreased, whereas the value of lactic acid and lactic acid to acetic acid ratio increased. The C40, C60, C80 and C100 silages’ Flieg score, used to evaluate the overall fermentation quality, was above 80 and higher than C0 (25) and C20 (61) silages. The C0 silage contained a complex bacterial community at the genus level, consisting mainly of Enterococcus (38.86%), Enterobacteria (20.61%), Rhizobium (8.45%), Lactobacillus (8.15%), Methylobacterium (5.54%) and Weissella (5.24%). As corn percentage increased from 0% to 40%, the relative abundance of desirable Lactobacillus increased and undesirable Rhizobium and Methylobacterium population reduced. With corn proportion in the mixture increasing from 0% to 40%, inclusion of corn to alfalfa at ensiling significantly improved silage fermentation quality and shifted the bacterial community for better silage preservation. Overall, high quality silage was produced when alfalfa was combined with at least 40% whole-plant corn on a fresh weight basis.

Persistent inflammation contributes to the development of cardiovascular disease (CVD) as an HIV-associated comorbidity. Innate immune cells such as monocytes are major drivers of inflammation in men and women with HIV. The study objectives are to examine the contribution of circulating non-classical monocytes (NCM, CD14dimCD16+) and intermediate monocytes (IM, CD14+CD16+) to the host response to long-term HIV infection and HIV-associated CVD. Women with and without chronic HIV infection (H) were studied. Subclinical CVD (C) was detected as plaques imaged by B-mode carotid artery ultrasound. The study included H-C-, H+C-, H-C+, and H+C+ participants (23 of each, matched on race/ethnicity, age and smoking status), selected from among enrollees in the Women's Interagency HIV Study. We assessed transcriptomic features associated with HIV or CVD alone or comorbid HIV/CVD comparing to healthy (H-C-) participants in IM and NCM isolated from peripheral blood mononuclear cells. IM gene expression was little affected by HIV alone or CVD alone. In IM, coexisting HIV and CVD produced a measurable gene transcription signature, which was abolished by lipid-lowering treatment. In NCM, versus non-HIV controls, women with HIV had altered gene expression, irrespective of whether or not they had comorbid CVD. The largest set of differentially expressed genes was found in NCM among women with both HIV and CVD. Genes upregulated in association with HIV included several potential targets of drug therapies, including LAG3 (CD223). In conclusion, circulating monocytes from patients with well controlled HIV infection demonstrate an extensive gene expression signature which may be consistent with the ability of these cells to serve as potential viral reservoirs. Gene transcriptional changes in HIV patients were further magnified in the presence of subclinical CVD.

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.

Introduction Maps are powerful tools for visualization of differences in health indicators by geographical region, but multi‐country maps of HIV indicators do not exist, perhaps due to lack of consistent data across countries. Our objective was to create maps of four HIV indicators in North, Central, and South American countries. Methods Using data from the North American AIDS Cohort Collaboration on Research and Design (NA‐ACCORD) and the Caribbean, Central, and South America network for HIV epidemiology (CCASAnet), we mapped median CD4 at presentation for HIV clinical care, proportion retained in HIV primary care, proportion prescribed antiretroviral therapy (ART), and the proportion with suppressed plasma HIV viral load (VL) from 2010 to 2012 for North, Central, and South America. The 15 Canadian and US clinical cohorts and 7 clinical cohorts in Argentina, Brazil, Chile, Haiti, Honduras, Mexico, and Peru represented approximately 2–7% of persons known to be living with HIV in these countries. Results Study populations were selected for each indicator: median CD4 at presentation for care was estimated among 14,811 adults; retention was estimated among 87,979 adults; ART use was estimated among 84,757 adults; and suppressed VL was estimated among 51,118 adults. Only three US states and the District of Columbia had a median CD4 at presentation >350 cells/mm3. Haiti, Mexico, and several states had >85% retention in care; lower (50–74%) retention in care was observed in the US West, South, and Mid‐Atlantic, and in Argentina, Brazil, and Peru. ART use was highest (90%) in Mexico. The percentages of patients with suppressed VL in the US South and Northeast were lower than in most of Central and South America. Conclusions These maps provide visualization of gaps in the quality of HIV care and allow for comparison between and within countries as well as monitoring policy and programme goals within geographical boundaries.

HIV-infected individuals are at increased risk of right and left heart dysfunction. N-terminal-pro-brain natriuretic peptide (NT-proBNP), a marker of cardiac ventricular strain and systolic dysfunction, may be associated with all-cause mortality in HIV-infected women. The aim of this study was to determine if elevated levels of NT-proBNP is associated with increased mortality in HIV-infected women.Prospective cohort study.We measured NT-proBNP in 936 HIV-infected and 387 age-matched HIV-uninfected women early (10/11/94 to 7/17/97) and 1082 HIV-infected and 448 HIV-uninfected women late (4/1/08 to 10/7/08) in the highly active antiretroviral therapy (HAART) periods in the Women's Interagency HIV Study. An NT-proBNP >75th percentile was more likely in HIV-infected persons, but only statistically significant in the late period (27% vs. 21%, unadjusted p = 0.03). In HIV-infected participants, NT-proBNP>75th percentile was independently associated with worse 5-year survival in the early HAART period (HR 1.8, 95% CI 1.3-2.4, p

BACKGROUND:U.S. state AIDS Drug Assistance Programs (ADAPs) are federally funded to provide antiretroviral therapy (ART) as the payer of last resort to eligible persons with HIV infection. States differ regarding their financial contributions to and ways of implementing these programs, and it remains unclear how this interstate variability affects HIV treatment outcomes. METHODS:We analyzed data from HIV-infected individuals who were clinically-eligible for ART between 2001 and 2009 (i.e., a first reported CD4+