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People with human immunodeficiency virus (HIV, PWH) face an increased risk of cardiovascular disease (CVD) compared to the general population. We previously demonstrated that people with (versus without) HIV have higher macrophage-specific arterial infiltration in relation to systemic monocyte activation. We now show that select T lymphocyte subpopulations (naïve CD4+, effector memory CD4+, and central memory CD8+) are differentially associated with macrophage-specific arterial infiltration among participants with versus without HIV, with evidence of interaction by HIV status. Our results suggest that among PWH, circulating T lymphocytes associate with macrophage-specific arterial infiltration, of relevance to atherogenesis and CVD risk. CLINICAL TRIALS REGISTRATION: NCT02542371.
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The intrauterine environment plays a critical role in shaping chronic disease risk over the life course. We prospectively evaluated cardiometabolic outcomes in toddlers born to mothers with versus without prenatal severe acute respiratory syndrome coronavirus 2 infection. Children with in utero severe acute respiratory syndrome coronavirus 2 exposure had higher left ventricular mass in association with altered maternal immunologic indices.
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OBJECTIVE: Tesamorelin is the only FDA-approved therapy to treat abdominal fat accumulation in people with HIV (PWH). Phase III clinical trials were conducted prior to the introduction of integrase inhibitors (INSTIs), which are now a mainstay of HIV antiretroviral therapy. DESIGN: We leveraged a randomized double-blind trial of 61 PWH and metabolic dysfunction-associated steatotic liver disease to evaluate the efficacy and safety of tesamorelin 2âmg once daily vs. identical placebo among participants on INSTI-based regimens at baseline. METHODS: In the parent clinical trial, visceral fat cross-sectional area, hepatic fat fraction, and trunk-to-appendicular fat ratio were quantified using magnetic resonance imaging, proton magnetic resonance spectroscopy, and dual-energy x-ray absorptiometry, respectively, at baseline and 12âmonths. Metabolic and safety outcomes were compared between treatment arms. RESULTS: Among 38 participants on INSTI-based regimens at baseline, 15 individuals on tesamorelin and 16 individuals on placebo completed the 12-month study. Tesamorelin led to significant declines in visceral fat (median [interquartile range]: -25 [-93, -2] vs. 14 [3, 41] cm 2 , P â=â0.001), hepatic fat (-4.2% [-12.3%, -2.7%] vs. -0.5% [-3.9%, 2.7%], P â=â0.01), and trunk-to-appendicular fat ratio (-0.1 [-0.3, 0.0] vs. 0.0 [-0.1, 0.1], P â=â0.03). Tesamorelin was well tolerated with a similar frequency of adverse events, including hyperglycemia, between groups. CONCLUSIONS: The current analysis provides the first dedicated data on the efficacy and safety of tesamorelin among PWH on INSTI-based regimens. Despite the association of INSTI use with weight gain and adipose tissue dysfunction, tesamorelin had beneficial effects on body composition with no exacerbation of glycemic control.
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Hormona Liberadora de Hormona del Crecimiento , Infecciones por VIH , Humanos , Masculino , Femenino , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/complicaciones , Persona de Mediana Edad , Método Doble Ciego , Hormona Liberadora de Hormona del Crecimiento/análogos & derivados , Hormona Liberadora de Hormona del Crecimiento/uso terapéutico , Hormona Liberadora de Hormona del Crecimiento/antagonistas & inhibidores , Adulto , Resultado del Tratamiento , Placebos/administración & dosificación , Imagen por Resonancia Magnética , Absorciometría de Fotón , Inhibidores de Integrasa VIH/uso terapéutico , Inhibidores de Integrasa VIH/efectos adversos , Efectos Colaterales y Reacciones Adversas Relacionados con MedicamentosRESUMEN
PURPOSE OF REVIEW: People with HIV (PWH) on antiretroviral therapy (ART) globally are disproportionately affected by obesity, with prevalence rates highest among women with HIV. The purpose of this review is to discuss rates of obesity, factors associated with obesity, and adverse consequences of obesity among PWH. RECENT FINDINGS: Among PWH on ART, rates of obesity have increased over the last several decades and tend to be higher than the general population. Weight gain with the initiation of new ART regimens such as integrase strand transfer inhibitor (INSTI)-based regimens are thought to contribute to higher rates of obesity among PWH on ART. Other factors, such as sex and ethnicity, also are associated with obesity among PWH on ART. Higher obesity rates among PWH may contribute to heightened cardiometabolic disease risk and lower health-related quality of life. SUMMARY: Prospective studies which identify factors associated with increased obesity prevalence and weight gain among PWH are necessary for the development and implementation of obesity prevention and treatment strategies among PWH on ART and, in turn, reduce the prevalence of obesity in this population.
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Infecciones por VIH , Inhibidores de Integrasa VIH , Humanos , Femenino , Estudios Prospectivos , Calidad de Vida , Infecciones por VIH/complicaciones , Infecciones por VIH/epidemiología , Obesidad/complicaciones , Obesidad/epidemiología , Aumento de PesoRESUMEN
BACKGROUND: Gender minorities and cisgender women face barriers to healthcare access. Prior work suggests cost may represent a particular barrier to accessing care for transgender and gender diverse (TGD) individuals. OBJECTIVE: To examine odds of delaying care for any reason and, secondarily, for 7 specific reasons among TGD individuals and cisgender women compared with cisgender men in the All of Us Research Program. DESIGN: We calculated the odds of delayed care by gender identity relative to cisgender men using multivariable-adjusted logistic regression, with adjustment for age, race, income, education, and Charlson comorbidity index. PARTICIPANTS: We examined 117,806 All of Us participants who completed the healthcare access and utilization survey. MAIN MEASURES: The primary outcome was self-reported delayed care in the past 12 months for any of 7 potential reasons: cost (out-of-pocket cost, co-payment costs, and/or high deductible), lack of childcare, lack of eldercare, nervousness associated with visiting the healthcare provider, rurality, inability to take time off work, and lack of transportation. KEY RESULTS: Compared with cisgender men, the multivariable-adjusted odds ratio (OR) for delaying care for any reason was 1.48 (95% CI, 1.44-1.53; P < 0.001) among cisgender women, 1.65 (95% CI, 1.24-2.21; P < 0.001) among TGD individuals assigned male at birth, and 2.76 (95% CI, 2.26-3.39; P < 0.001) among TGD individuals assigned female at birth. Results were consistent across multiple sensitivity analyses. TGD individuals were substantially more likely to cite nervousness with visiting a healthcare provider as a barrier, whereas cisgender women were more likely to delay care due to lack of childcare coverage. CONCLUSIONS: Cisgender women and TGD individuals were more likely to delay seeking heath care compared with cisgender men, and for partially different reasons. These findings highlight the need to address common and distinct barriers to care access among marginalized groups.
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Plasma vascular endothelial growth factor (VEGF) coreceptor neuropilin-1 (NRP-1) had the largest association with coronary plaque in the Randomized Trial to Prevent Vascular Events in HIV (REPRIEVE) proteomics analysis. With little known about NRP-1 in people with human immunodeficiency virus (PWH), we explored its relation to other proteins in REPRIEVE and validated our findings through a Centers for AIDS Research Network of Integrated Clinical Systems (CNICS) case-cohort study by assessing its relation to host factors and incident cardiovascular disease and cancer. Within REPRIEVE, NRP-1 was associated with proteins involved in angiogenesis, signal transduction, immunoregulation, and cell migration/adhesion. Within CNICS, NRP-1 was associated with key host factors, including older age and male sex. NRP-1 was associated with an increased hazard of multiple cancers but a decreased prostate cancer risk. Finally, NRP-1 was most strongly associated with mortality and type 2 myocardial infarction. These data suggest that NRP-1 is part of a clinically relevant immunoregulatory pathway related to multiple comorbidities in PWH. Clinical Trials Registration. NCT02344290.
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BACKGROUND: Sodium-glucose transporter 2 (SGLT2) inhibitors have been approved for treatment of diabetes mellitus (DM), chronic kidney disease, and heart failure, but little is known about prescription levels and safety profiles among people with HIV (PWH). METHODS: We leveraged data from the US Mass General Brigham electronic healthcare database to determine the use/uptake of SGLT2 inhibitors among PWH with type II diabetes (DM2) (with or without chronic kidney disease, proteinuria, or heart failure) and to assess rates of adverse events among PWH with DM2 taking SGLT2 inhibitors. RESULTS: Among eligible PWH with DM2 receiving care at US Mass General Brigham (N = 907), SGLT2 inhibitors were prescribed to 8.8%. SGLT2 inhibitors were prescribed to a fraction of eligible PWH with DM2 and a concomitant diagnosis of chronic kidney disease (3.8%), proteinuria (13.2%), or heart failure (8.2%). PWH with DM2 on SGLT2 inhibitors experienced side effects (urinary tract infection, diabetic ketoacidosis, and acute kidney injury) at rates comparable with PWH with DM2 prescribed glucagon-like peptide-1 agonists. Rates of mycotic genitourinary infections were higher among those prescribed SGLT2 inhibitors (5% vs. 1%, P = 0.17), but no cases of necrotizing fasciitis ensued. CONCLUSIONS: Additional studies are needed to characterize population-specific salutary and adverse effects of SGLT2 inhibitors among PWH and potentially augment prescription rates when guideline indicated.
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Diabetes Mellitus Tipo 2 , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Infecciones por VIH , Insuficiencia Cardíaca , Insuficiencia Renal Crónica , Inhibidores del Cotransportador de Sodio-Glucosa 2 , Humanos , Inhibidores del Cotransportador de Sodio-Glucosa 2/efectos adversos , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Infecciones por VIH/complicaciones , Infecciones por VIH/tratamiento farmacológico , Insuficiencia Renal Crónica/complicaciones , Insuficiencia Renal Crónica/inducido químicamente , Insuficiencia Cardíaca/complicaciones , Proteinuria , Hipoglucemiantes/uso terapéuticoRESUMEN
BACKGROUND: People with human immunodeficiency virus (HIV) have heightened incidence/risk of diastolic dysfunction and heart failure. Women with HIV have elevated cardiac fibrosis, and plasma osteopontin (Opn) is correlated to cardiac pathology. Therefore, this study provides mechanistic insight into the relationship between osteopontin and cardiac fibrosis during HIV infection. METHODS: Mouse embryonic fibroblasts (MEFs) modeled cardiac fibroblasts in vitro. Simian immunodeficiency virus (SIV)-infected macaques with or without antiretroviral therapy and HIV-infected humanized mice modeled HIV-associated cardiac fibrosis. RESULTS: Lipopolysaccharide-stimulated MEFs were myofibroblast-like, secreted cytokines, and produced Opn transcripts. SIV-infected animals had elevated plasma Opn at necropsy, full-length Opn in the ventricle, and ventricular interstitial fibrosis. Regression modeling identified growth differentiation factor 15, CD14+CD16+ monocytes, and CD163 expression on CD14+CD16+ monocytes as independent predictors of plasma Opn during SIV infection. HIV-infected humanized mice showed increased interstitial fibrosis compared to uninfected/untreated animals, and systemic inhibition of osteopontin by RNA aptamer reduced left ventricle fibrosis in HIV-infected humanized mice. CONCLUSIONS: Since Opn is elevated in the plasma and left ventricle during SIV infection and systemic inhibition of Opn reduced cardiac fibrosis in HIV-infected mice, Opn may be a potential target for adjunctive therapies to reduce cardiac fibrosis in people with HIV.
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Cardiomiopatías , Infecciones por VIH , Síndrome de Inmunodeficiencia Adquirida del Simio , Virus de la Inmunodeficiencia de los Simios , Humanos , Animales , Femenino , Ratones , Infecciones por VIH/patología , Osteopontina/genética , Osteopontina/metabolismo , Fibroblastos , Corazón , Cardiomiopatías/patología , Virus de la Inmunodeficiencia de los Simios/fisiología , Fibrosis , Macaca/metabolismo , VIHRESUMEN
CONTEXT: Since the initial outbreak of coronavirus disease 2019 (COVID-19), a novel population of children with in utero exposure to maternal infection has emerged whose health outcomes are largely unknown. OBJECTIVE: To compare longitudinal growth trajectories among infants with vs without in utero COVID-19 exposure. METHODS: We conducted a longitudinal cohort study leveraging a prospectively enrolled perinatal biorepository among 149 infants with in utero COVID-19 exposure and 127 unexposed controls. Weight, length, and body mass index (BMI) were abstracted from health records at 0, 2, 6, and 12 months and standardized using World Health Organization growth charts. Analyses were adjusted for maternal age, ethnicity, parity, insurance, and BMI as well as infant sex, birthdate, and breastfeeding. RESULTS: Infants with in utero COVID-19 exposure vs controls exhibited differential trajectories of weight and BMI, but not length, z-score over the first year of life (study group × time interaction, P < .0001 for weight and BMI). Infants born to mothers with prenatal COVID-19 had lower BMI z-score at birth (effect size: -0.35, 95% CI -0.66 to -0.03) and greater gain in BMI z-score from birth to 12 months (effect size: 0.53, 95% CI 0.06 to 0.99). Birth weight z-score mediated a significant proportion of the relationship between COVID-19 exposure and postnatal growth (estimate ± SE, 32 ± 14%, P = .02). CONCLUSION: Infants with in utero COVID-19 exposure exhibited lower birth weight and accelerated weight gain in the first year of life, which may be harbingers of downstream cardiometabolic pathology. Further studies are needed to delineate cardiometabolic sequelae among this emerging global population.
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COVID-19 , Enfermedades Cardiovasculares , Recién Nacido , Niño , Femenino , Embarazo , Lactante , Humanos , Estudios Longitudinales , Peso al Nacer , COVID-19/epidemiología , Aumento de Peso , Índice de Masa CorporalAsunto(s)
Cardiología , Sistema Cardiovascular , Minorías Sexuales y de Género , Humanos , Políticas , Recursos HumanosRESUMEN
Purpose: Through a survey-based approach, we sought to investigate regional differences in gender-affirming hormone therapy (GAHT) prescribing practices, as well as HIV screening and prevention practices among clinicians providing care to transgender individuals. Methods: Our survey was disseminated between December 2019 and January 2021 to clinicians who prescribe GAHT within New England (United States). Between-group differences in GAHT prescribing and HIV screening/prevention practices were evaluated by practice setting and subspecialty. Results: Of the 20 survey respondents, 55% practiced in health care settings affiliated with an academic institution, 45% practiced in a community-based health care setting, and 30% were Endocrinologists. Clinicians in community-based health care settings reported more frequently prescribing oral 17ß-estradiol (p=0.02) and spironolactone (p=0.007) for feminizing GAHT compared with clinicians in health care settings affiliated with an academic institution, who reported more frequently prescribing leuprolide (p=0.03). For masculinizing GAHT, clinicians from health care settings affiliated with an academic institution reported more frequently prescribing topical testosterone (p=0.03). There were no significant between-group differences in reported barriers to initiation or reasons for stopping GAHT. While non-Endocrinologists reported "often" or "always" offering HIV screening, most Endocrinologists reported "rarely" or "never" offering HIV screening and "rarely" or "never" offering pre-exposure or postexposure prophylaxis to their transgender patients. Conclusions: Regional GAHT prescribing practices varied by setting. Additional research is needed to better understand whether these differences translate to differences in GAHT efficacy and side-effects. Further, HIV screening/prevention practices varied by subspecialty. Integrated GAHT and HIV screening/prevention across subspecialties could help reduce the disproportionate burden of HIV faced by the transgender community.
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OBJECTIVE: Accumulating evidence demonstrates that gender affirming hormone therapy (GAHT) improves mental health outcomes in transgender persons. Data specific to the risks associated with GAHT for transgender persons continue to emerge, allowing for improvements in understanding, predicting, and mitigating adverse outcomes while informing discussion about desired effects. Of particular concern is the risk of venous thromboembolism (VTE) in the context of both longitudinal GAHT and the perioperative setting. Combining what is known about the risk of VTE in cisgender individuals on hormone therapy (HT) with the evidence for transgender persons receiving HT allows for an informed approach to assess underlying risk and improve care in the transgender community. OBSERVATIONS: Hormone formulation, dosing, route, and duration of therapy can impact thromboembolic risk, with transdermal estrogen formulations having the lowest risk. There are no existing risk scores for VTE that consider HT as a possible risk factor. Risk assessment for recurrent VTE and bleeding tendencies using current scores may be helpful when assessing individual risk. Gender affirming surgeries present unique perioperative concerns, and certain procedures include a high likelihood that patients will be on exogenous estrogens at the time of surgery, potentially increasing thromboembolic risk. CONCLUSIONS AND RELEVANCE: Withholding GAHT due to potential adverse events may cause negative impacts for individual patients. Providers should be knowledgeable about the management of HT in transgender individuals of all ages, as well as in the perioperative setting, to avoid periods in which transgender individuals are off GAHT. Treatment decisions for both anticoagulation and HT should be individualized and tailored to patients' overall goals and desired outcomes, given that the physical and mental health benefits of gender affirming care may outweigh the risk of VTE.
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Personas Transgénero , Transexualidad , Tromboembolia Venosa , Humanos , Tromboembolia Venosa/epidemiología , Tromboembolia Venosa/inducido químicamente , Identidad de Género , Personas Transgénero/psicología , Transexualidad/terapia , EstradiolRESUMEN
BACKGROUND: Human immunodeficiency virus (HIV)-associated nonalcoholic fatty liver disease (NAFLD) is characterized by a high prevalence of hepatic fibrosis as a strong clinical predictor of all-cause and liver-specific mortality risk. METHODS: We leveraged data from an earlier clinical trial to define the circulating proteomic signature of hepatic fibrosis in HIV-associated NAFLD. A total of 183 plasma proteins within 2 high-multiplex panels were quantified at baseline and at 12 months (Olink Cardiovascular III; Immuno-Oncology). RESULTS: Twenty proteins were up-regulated at baseline among participants with fibrosis stages 2-3 versus 0-1. Proteins most differentially expressed included matrix metalloproteinase 2 (P < .001), insulin-like growth factor-binding protein 7 (P = .001), and collagen α1(I) chain (P = .001). Proteins were enriched within pathways including response to tumor necrosis factor and aminopeptidase activity. Key proteins correlated directly with visceral adiposity and glucose intolerance and inversely with CD4+ T-cell count. Within the placebo-treated arm, 11 proteins differentially increased among individuals with hepatic fibrosis progression over a 12-month period (P < .05). CONCLUSIONS: Among individuals with HIV-associated NAFLD, hepatic fibrosis was associated with a distinct proteomic signature involving up-regulation of tissue repair and immune response pathways. These findings enhance our understanding of potential mechanisms and biomarkers of hepatic fibrosis in HIV.
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Infecciones por VIH , Enfermedad del Hígado Graso no Alcohólico , Humanos , Enfermedad del Hígado Graso no Alcohólico/complicaciones , Metaloproteinasa 2 de la Matriz/metabolismo , Regulación hacia Arriba , VIH , Proteómica , Cirrosis Hepática/etiología , Hígado/patología , Infecciones por VIH/patología , InmunidadRESUMEN
OBJECTIVE: Women with HIV (WWH) have heightened heart failure risk. Plasma OPN (osteopontin) is a powerful predictor of heart failure outcomes in the general population. Limited data exist on relationships between plasma OPN and surrogates of HIV-associated heart failure risk. DESIGN: Prospective, cross-sectional. METHODS: We analyzed relationships between plasma OPN and cardiac structure/function (assessed using cardiovascular magnetic resonance imaging) and immune activation (biomarkers and flow cytometry) among 20 WWH and 14 women without HIV (WWOH). RESULTS: Plasma OPN did not differ between groups. Among WWH, plasma OPN related directly to the markers of cardiac fibrosis, growth differentiation factor-15 (ρâ=â0.51, Pâ=â0.02) and soluble interleukin 1 receptor-like 1 (ρâ=â0.45, Pâ=â0.0459). Among WWH (but not among WWOH or the whole group), plasma OPN related directly to both myocardial fibrosis (ρâ=â0.49, Pâ=â0.03) and myocardial steatosis (ρâ=â0.46, Pâ=â0.0487). Among the whole group and WWH (and not among WWOH), plasma OPN related directly to the surface expression of C-X3-C motif chemokine receptor 1 (CX3CR1) on nonclassical (CD14-CD16+) monocytes (whole group: ρâ=â0.36, Pâ=â0.04; WWH: ρâ=â0.46, Pâ=â0.04). Further, among WWH and WWOH (and not among the whole group), plasma OPN related directly to the surface expression of CC motif chemokine receptor 2 (CCR2) on inflammatory (CD14+CD16+) monocytes (WWH: ρâ=â0.54, Pâ=â0.01; WWOH: ρâ=â0.60, Pâ=â0.03), and in WWH, this held even after controlling for HIV-specific parameters. CONCLUSION: Among WWH, plasma OPN, a powerful predictor of heart failure outcomes, related to myocardial fibrosis and steatosis and the expression of CCR2 and CX3CR1 on select monocyte subpopulations. OPN may play a role in heart failure pathogenesis among WWH. CLINICALTRIALSGOV REGISTRATION: NCT02874703.
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Infecciones por VIH , Insuficiencia Cardíaca , Humanos , Femenino , Osteopontina/metabolismo , Estudios Transversales , Estudios Prospectivos , Infecciones por VIH/complicaciones , Fibrosis , Receptores de Quimiocina , Monocitos/metabolismoRESUMEN
BACKGROUND: Women with HIV (WWH) face heightened risks of heart failure; however, insights on immune/inflammatory pathways potentially contributing to left ventricular (LV) systolic dysfunction among WWH remain limited. SETTING: Massachusetts General Hospital, Boston, Massachusetts. METHODS: Global longitudinal strain (GLS) is a sensitive measure of LV systolic function, with lower cardiac strain predicting incident heart failure and adverse heart failure outcomes. We analyzed relationships between GLS (cardiovascular magnetic resonance imaging) and monocyte activation (flow cytometry) among 20 WWH and 14 women without HIV. RESULTS: WWH had lower GLS compared to women without HIV (WWH vs. women without HIV: 19.4±3.0 vs. 23.1±1.9%, P<0.0001). Among the whole group, HIV status was an independent predictor of lower GLS. Among WWH (but not among women without HIV), lower GLS related to a higher density of expression of HLA-DR on the surface of CD14+CD16+ monocytes (ρ = -0.45, P = 0.0475). Further, among WWH, inflammatory monocyte activation predicted lower GLS, even after controlling for CD4+ T-cell count and HIV viral load. CONCLUSIONS: Additional studies among WWH are needed to examine the role of inflammatory monocyte activation in the pathogenesis of lower GLS and to determine whether targeting this immune pathway may mitigate risks of heart failure and/or adverse heart failure outcomes. TRIAL REGISTRATION: Clinical trials.gov registration: NCT02874703.
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Infecciones por VIH , Insuficiencia Cardíaca , Disfunción Ventricular Izquierda , Humanos , Femenino , Monocitos , Corazón , Función Ventricular Izquierda/fisiología , Volumen Sistólico/fisiologíaRESUMEN
BACKGROUND: Persistent immune activation is thought to contribute to heightened atherosclerotic cardiovascular disease (ASCVD) risk among people with human immunodeficiency virus (PWH). METHODS: Participants (≥18 years) with or without human immunodeficiency virus (HIV) and without history of clinical ASCVD were enrolled. We hypothesized that increased macrophage-specific arterial infiltration would relate to plaque composition and systemic immune activation among PWH. We applied a novel targeted molecular imaging approach (technetium-99m [99mTc]-tilmanocept single photon emission computed tomography [SPECT]/CT) and comprehensive immune phenotyping. RESULTS: Aortic 99mTc-tilmanocept uptake was significantly higher among PWH (n = 20) than participants without HIV (n = 10) with similar 10-year ASCVD risk (P = .02). Among PWH, but not among participants without HIV, noncalcified aortic plaque volume related directly to aortic 99mTc-tilmanocept uptake at different uptake thresholds. An interaction (P = .001) was seen between HIV status and noncalcified plaque volume, but not calcified plaque (P = .83). Systemic levels of caspase-1 (P = .004), CD14-CD16+ (nonclassical/patrolling/homing) monocytes (P = .0004) and CD8+ T cells (P = .005) related positively and CD4+/CD8+ T-cell ratio (P = .02) inversely to aortic 99mTc-tilmanocept uptake volume. CONCLUSIONS: Macrophage-specific arterial infiltration was higher among PWH and related to noncalcified aortic plaque volume only among PWH. Key systemic markers of immune activation relating to macrophage-specific arterial infiltration may contribute to heightened ASCVD risk among PWH. CLINICAL TRIALS REGISTRATION: NCT02542371.
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Aterosclerosis , Infecciones por VIH , Placa Aterosclerótica , Humanos , Placa Aterosclerótica/diagnóstico por imagen , Infecciones por VIH/tratamiento farmacológico , Macrófagos , VIHRESUMEN
Hematopoietic stem cells (HSCs) are polyfunctional, regenerating all blood cells via hematopoiesis throughout life. Clonal hematopoiesis (CH) is said to occur when a substantial proportion of mature blood cells is derived from a single dominant HSC lineage, usually because these HSCs have somatic mutations that confer a fitness and expansion advantage. CH strongly associates with aging and enrichment in some diseases irrespective of age, emerging as an independent causal risk factor for hematologic malignancies, cardiovascular disease, adverse disease outcomes, and all-cause mortality. Defining the molecular mechanisms underlying CH will thus provide a framework to develop interventions for healthy aging and disease treatment. Here, we review the most recent advances in understanding the molecular basis of CH in health and disease.
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Hematopoyesis Clonal , Neoplasias Hematológicas , Hematopoyesis Clonal/genética , Neoplasias Hematológicas/genética , Hematopoyesis/genética , Células Madre Hematopoyéticas , Humanos , MutaciónRESUMEN
PURPOSE OF REVIEW: Transgender individuals are at disproportionate risk for HIV infection, with prevalence rates highest among transgender women of color. Antiretroviral therapy (ART)-treated people with HIV (PWH) are at increased risk for cardiovascular disease (CVD), in relation to persistent systemic immune activation and metabolic dysregulation. The purpose of this review is to examine parameters which may affect CVD risk among transgender PWH. RECENT FINDINGS: Among transgender women and men, prospective longitudinal studies have shown that gender-affirming hormonal therapy (GAHT) is associated with select deleterious cardiometabolic effects such as increases in visceral adipose tissue. Retrospective studies among transgender women and men suggest an increase in CVD risk, such as venous thromboembolism, cerebrovascular accidents, and myocardial infarction. Studies among transgender PWH adhering to GAHT and ART suggest heightened systemic immune activation/inflammation. Prospective longitudinal studies assessing factors associated with increased CVD events among transgender PWH are needed to guide the development of CVD prevention strategies in this at-risk population.
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Enfermedades Cardiovasculares , Infecciones por VIH , Personas Transgénero , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/etiología , Femenino , Infecciones por VIH/complicaciones , Infecciones por VIH/tratamiento farmacológico , Factores de Riesgo de Enfermedad Cardiaca , Humanos , Masculino , Estudios Prospectivos , Estudios RetrospectivosRESUMEN
Women with HIV (WWH) transitioning through menopause have heightened cardiovascular disease (CVD) risk. In the general population, hot flash burden relates to CVD risk indices. We found higher hot flash burden among women with vs without HIV. Further, among WWH, hot flash burden related to select CVD risk indices. CLINICALTRIALSGOV REGISTRATION: NCT02874703.
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The NOD-like receptor protein family pyrin domain containing 3 (NLRP3) inflammasome, activated in the setting of HIV, contributes to pro-atherogenic inflammation. Among antriretroviral therapy-naïve people with HIV (vs controls), levels of caspase-1-a key component of the NLRP3 inflammasome-were significantly increased. Six months of elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate significantly decreased caspase-1 levels in association with CD4+/CD8+ ratio recovery.Trial registration. ClinicalTrials.gov NCT01766726.