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BackgroundPeople with HIV (PWH) have an increased risk of cardiovascular disease (CVD). Cardiac magnetic resonance (CMR) has documented higher myocardial fibrosis, inflammation and steatosis in PWH, but studies have mostly relied on healthy volunteers as comparators and focused on men.MethodsWe investigated the associations of HIV and HIV-specific factors with CMR phenotypes in female participants enrolled in the Women's Interagency HIV Study's New York and San Francisco sites. Primary phenotypes included myocardial native (n) T1 (fibro-inflammation), extracellular volume fraction (ECV, fibrosis) and triglyceride content (steatosis). Associations were evaluated with multivariable linear regression, and results pooled or meta-analyzed across centers.ResultsAmong 261 women with HIV (WWH, total n = 362), 76.2% had undetectable viremia at CMR. For the 82.8% receiving continuous antiretroviral therapy (ART) in the preceding 5 years, adherence was 51.7%, and 71.3% failed to achieve persistent viral suppression (42.2% with peak viral load

BackgroundHeavy drinking, smoking, and depression are common among people with HIV. Little is known about the co-occurring, synergistic effect of having two or more of these conditions long-term -a sustained syndemic - on mortality among women with HIV (WWH).MethodsData from 3282 WWH of the Women's Interagency HIV Study from 1994 to 2017 were utilized. National Death Index review identified cause of death (n=616). Sustained syndemic phenotypes were based on membership in high-risk groups defined by group-based trajectory models of repeated self-reported alcohol use, smoking, and depressive symptoms and their co-occurrence. Cox proportional hazard models estimated associations of sustained syndemic phenotypes with all-cause, non-AIDS, and non-overdose mortality, adjusting for age, race/ethnicity, education, enrollment wave, illicit drug use, and time-varying HIV viral load and CD4+ T-cell count.ResultsWWH were 58% Black and 26% Hispanic, with a mean baseline age of 36.7 years. Syndemic phenotypes included zero (45%, n=1463), heavy drinking only (1%, n=35), smoking only (28%, n=928), depressive symptoms only (9%, n=282), and 2+ trajectories (17%, n=574). Compared to zero trajectories, having 2+ trajectories was associated with 3.93 times greater all-cause mortality risk (95% CI 3.07, 5.04) after controlling for confounders and each high-risk trajectory alone. These findings persisted in sensitivity analyses, removing AIDS- and overdose-related mortalities.ConclusionsClustering of 2+ conditions of heavy drinking, smoking, and depression affected nearly one in five WWH and was associated with higher mortality than zero or one condition. Our findings underscore the need for coordinated screening and parsimonious treatment strategies for these co-occurring conditions.

Heart failure is a prevalent disorder whose prognosis remains poor despite advances in treatment. Women with or at risk for HIV may be particularly susceptible, yet the metabolic pathways that promote myocardial disease and heart failure in this context remain incompletely characterized.To evaluate the metabolomic signatures of cardiac magnetic resonance measured phenotypes, we used available plasma metabolomic measures from participants in the Women's Interagency HIV Study who underwent cardiac magnetic resonance imaging. Our primary outcomes were myocardial extracellular volume fraction (MECV) and intramyocardial triglyceride content (IMTG). We applied partial least squares and identified the top 10 lipid and polar metabolites associated with MECV and IMTG. We used multivariable linear regression to evaluate these metabolites' individual associations with each phenotype.The mean age of participants (n = 153) was 53 ± 7, 93% were Black or Hispanic, and 74% were HIV positive. Phenylacetylglutamine, a microbial metabolite, was positively associated with MECV after full adjustment and false discovery rate correction. Three phosphatidylcholine species, N-acetylaspartic acid, and a lysophosphatidylcholine species were inversely associated with IMTG, while prolylglycine, methionine sulfoxide, sphingosine, taurine, and phosphorylcholine were positively associated with this phenotype. We found no evidence of interaction by HIV for the observed associations, but there was effect modification by hepatitis C virus of taurine's and phosphorylcholine's associations with IMTG.Among women with or at risk for HIV, we related various lipid and polar metabolites to cardiac fibrosis or steatosis, of which phenylacetylglutamine, N-acetylaspartic acid, and prolylglycine are novel. These findings implicate plausible mechanisms that could be targetable for therapeutics.

The original article [1] contained significant errors in Fig 1A which necessitated correction; the figure has since been updated to the corrected version.

BackgroundCryopreserved 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.ResultsAmong 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.ConclusionsIn conclusion, combined protein and transcript scRNA sequencing is a suitable and powerful method for clinical investigations using PBMCs.

ObjectiveAmong 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.DesignNested cohort study.MethodsParticipants 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.ResultsAmong 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.ConclusionCarotid artery plaque was predictive of mortality, with differences observed by sex and HIV serostatus.

BackgroundMonocytes and monocyte-derived macrophages promote atherosclerosis through increased inflammation and vascular remodeling. This may be especially true in chronic human immunodeficiency virus (HIV) infection.MethodsWe examined 778 women (74% HIV+) in the Women's Interagency HIV Study and 503 men (65% HIV+) in the Multicenter AIDS Cohort Study who underwent repeated B-mode carotid artery ultrasound imaging in 2004-2013. We assessed baseline associations of the serum macrophage inflammation markers soluble (s)CD163, sCD14, galectin-3 (Gal-3), and Gal-3 binding protein (Gal-3BP) with carotid plaque formation (focal intima-media thickness >1.5 mm) over 7 years.ResultsMarker levels were higher in HIV+ persons versus HIV- persons. Presence of focal plaque increased over time: from 8% to 15% in women, and 24% to 34% in men. After adjustment for demographic, behavioral, and cardiometabolic factors, and CRP and interleukin-6, each standard deviation increase in sCD14 was associated with increased plaque formation (risk ratio [RR] 1.24, 95% confidence interval [CI] 1.07-1.43). This pattern was consistentby sex. sCD163 was associated with plaque formation in virally suppressed HIV+ men (RR 1.52, 95% CI 1.04-2.22); Gal-3BP and Gal-3 were not associated with increased plaque.ConclusionssCD14 and sCD163 may play important roles in atherogenesis among HIV+ persons.

Introduction: Nocturia is a complex and multifactorial condition, associated with several genitourinary abnormalities as well as a host of conditions beyond the urinary tract, and thus often poses a significant diagnostic challenge in real‐world practice. Sleep Disorders, Comorbidities, Actions, Lower Urinary Tract Dysfunction, and Medications, the so‐called "Sleep C.A.L.M." factors, are five common causes of nocturia requiring judicious evaluation according to current consensus guidelines. This study aims to assess the prevalence of the Sleep C.A.L.M. factors in a nocturia clinical population. Methods: Retrospective analysis of frequency‐volume charts from men with ≥2 nocturnal voids as well as concurrent demographic, clinical, and medical history data to identify patients with each of the Sleep C.A.L.M. factors. Comorbidities and medications were classified as a single group. Results: A total of 213 subjects met the criteria for inclusion (median age 68.0 [63.5‐75.5] years). The prevalence of 1) sleep disorders, 2) comorbidities and/or medication use, 3) actions (i.e., modifiable behaviors/lifestyle factors), and 4) lower urinary tract dysfunction was 31%, 31%, 19%, and 41%, respectively. Among included participants, 73% were found to have at least 1 Sleep C.A.L.M. factor, and 33% had multiple Sleep C.A.L.M. factors. Results were similar upon stratification by age and nocturnal polyuria status. Conclusions: The Sleep C.A.L.M. factors are highly common among nocturia patients in the clinical urology setting. Although many of these factors are strongly associated with advanced age in community‐based nocturia study samples, they appear common even among younger men in a nocturia patient population; the differential effect of age and individual Sleep C.A.L.M. factors on nocturia pathophysiology requires further investigation. [ABSTRACT FROM AUTHOR]

BackgroundIndividuals infected with human immunodeficiency virus (HIV) live longer as a result of effective treatment, but long-term consequences of infection, treatment, and immunological dysfunction are poorly understood.MethodsWe prospectively examined 1011 women (74% HIV-infected) in the Women's Interagency HIV Study and 811 men (65% HIV-infected) in the Multicenter AIDS Cohort Study who underwent repeated B-mode carotid artery ultrasound imaging in 2004-2013. Outcomes included changes in right common carotid artery intima-media thickness (CCA-IMT) and new focal carotid artery plaque formation (IMT >1.5 mm) over median 7 years. We assessed the association between HIV serostatus and progression of subclinical atherosclerosis, adjusting for demographic, behavioral, and cardiometabolic risk factors.ResultsUnadjusted mean CCA-IMT increased (725 to 752 µm in women, 757 to 790 µm in men), but CCA-IMT progression did not differ by HIV serostatus, either in combined or sex-specific analyses. Focal plaque prevalence increased from 8% to 15% in women and 25% to 34% in men over 7 years. HIV-infected individuals had 1.6-fold greater risk of new plaque formation compared with HIV-uninfected individuals (relative risk [RR] 1.61, 95% CI, 1.12-2.32), adjusting for cardiometabolic factors; the association was similar by sex. Increased plaque occurred even among persistently virologically suppressed HIV-infected individuals compared with uninfected individuals (RR 1.56, 95% CI, 1.07-2.27). HIV-infected individuals with baseline CD4+ ≥ 500 cells/µL had plaque risk not statistically different from uninfected individuals.ConclusionsHIV infection is associated with greater increases in focal plaque among women and men, potentially mediated by factors associated with immunodeficiency or HIV replication at levels below current limits of detection.