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The COVID-19 pandemic has profoundly influenced the effort to achieve global health equity. This has been particularly the case for HIV/AIDS, tuberculosis, and malaria control initiatives in low- and middle-income countries, with significant outcome setbacks seen for the first time in decades. Lost in the calls for compensatory funding increases for such programs, however, is the plight of endemic tropical heart diseases, a group of disorders that includes rheumatic heart disease, Chagas disease, and endomyocardial fibrosis. Such endemic illnesses affect millions of people around the globe and remain a source of substantial mortality, morbidity, and health disparity. Unfortunately, these conditions were already neglected before the pandemic, and thus those living with them have disproportionately suffered during the time of COVID-19. In this perspective, we briefly define endemic tropical heart diseases, summarizing their prepandemic epidemiology, funding, and control statuses. We then describe the ways in which people living with these disorders, along with the healthcare providers and researchers working to improve their outcomes, have been harmed by the ongoing COVID-19 pandemic. We conclude by proposing the path forward, including approaches we may use to leverage lessons learned from the pandemic to strengthen care systems for these neglected diseases.

Low-density lipoprotein cholesterol (LDL-C) is typically estimated from total cholesterol, high-density lipoprotein cholesterol, and triglycerides. The Friedewald, Martin-Hopkins, and National Institutes of Health equations are widely used but may estimate LDL-C inaccurately in certain patient populations, such as those with HIV. We sought to investigate the utility of machine learning for LDL-C estimation in a large cohort of women with and without HIV.We identified 7397 direct LDL-C measurements (5219 from HIV-infected individuals, 2127 from uninfected controls, and 51 from seroconvertors) from 2414 participants (age 39.4 ± 9.3 years) in the Women's Interagency HIV Study and estimated LDL-C using the Friedewald, Martin-Hopkins, and National Institutes of Health equations. We also optimized 5 machine learning methods [linear regression, random forest, gradient boosting, support vector machine (SVM), and neural network] using 80% of the data (training set). We compared the performance of each method using root mean square error, mean absolute error, and coefficient of determination (R2) in the holdout (20%) set.SVM outperformed all 3 existing equations and other machine learning methods, achieving the lowest root mean square error and mean absolute error, and the highest R2 (11.79 and 7.98 mg/dL, 0.87, respectively, compared with those obtained using the Friedewald equation: 12.45 and 9.14 mg/dL, 0.87). SVM performance remained superior in subgroups with and without HIV, with nonfasting measurements, in LDL70 mg/dL and triglycerides400 mg/dL.In this proof-of-concept study, SVM is a robust method that predicts directly measured LDL-C more accurately than clinically used methods in women with and without HIV. Further studies should explore the utility in broader populations.

People with HIV (PWH) experience a high frequency of symptoms that are associated with poor clinical outcomes. We conducted a secondary analysis of data from an observational study to examine whether diet, muscle strength, or physical activity were associated with symptoms among PWH and their HIV-uninfected peers. One-hundred ninety-one individuals (105 PWH and 86 HIV uninfected) with similar age and race were included. Symptoms were examined using the Patient-Reported Outcomes Measurement Information System (PROMIS-29) questionnaire, for which lower scores indicate higher function or fewer symptoms. The total healthy eating index score and carbohydrates, sugar sweet beverages, alcohol, and fiber consumption per day were obtained through 24-hour dietary recalls. A dynamometer was used to determine muscle strength. Steps per day were examined through 7 days of actigraphy. Linear regression analyses were used to determine the relationship between symptoms and diet, muscle strength, and steps per day. Participants were, on average, 54 years, 83% were African American, and 58% were male. In PWH, less healthy eating, fiber intake, and muscle strength were associated with poorer physical function; more steps per day were associated with fatigue; less daily carbohydrate consumption was associated with more pain. HIV-uninfected individuals demonstrated an association between fewer steps per day and poorer physical function and more pain, and less carbohydrate intake and more sleep disturbance. The relationships between diet, muscle strength, steps per day and PROMIS-29 health domains differed by HIV status.

BACKGROUND People with HIV (PWH) are at an increased risk of both heart and kidney disease, but the relationship between kidney disease and cardiac structure and function in this population has not been well studied. In particular, whether the relationship between kidney disease and cardiac structure and function is stronger for PWH compared with uninfected controls is unknown. METHODS One hundred PWH on antiretroviral therapy were compared with 100 age-matched and sex-matched controls without HIV in Uganda. Multivariable regression models were used to examine associations between creatinine-based and cystatin C-based estimated glomerular filtration rate (eGFR), albumin-creatinine ratio, and echocardiographic measures of cardiac structure and function. RESULTS PWH had lower eGFRcr (β -7.486, 95% confidence interval: -13.868 to -1.104, P = 0.022) and a higher rate of albumin-creatinine ratio ≥30 (odds ratio 2.146, 95% confidence interval: 1.027 to 4.484, P = 0.042) after adjustment for traditional risk factors. eGFR was inversely associated with both left ventricular mass index and diastolic dysfunction in adjusted models but not with systolic function. Albuminuria was associated with more diastolic dysfunction among PWH but not controls (P for interaction = 0.046). The association of HIV with a higher left ventricular mass index (P = 0.005) was not substantially affected by adjusting for eGFRcr. CONCLUSION Among Ugandans, eGFR is associated with elevated LV mass and diastolic dysfunction. The association between albuminuria and diastolic dysfunction is particularly strong for PWH.

Background After achieving viral suppression, it is critical for persons living with HIV (PLWH) to focus on prevention of non-AIDS comorbidities such as cardiovascular disease (CVD) in order to enhance their quality of life and longevity of life. Despite PLWH elevated risk of developing CVD compared to individuals without HIV, PLWH do not often meet evidence-based treatment goals for CVD prevention; the reasons for PLWH not meeting guideline recommendations are poorly understood. The objective of this study was to identify the factors associated with adherence to CVD medications for PLWH who have achieved viral suppression. Methods Qualitative data were obtained from formative research conducted to inform the adaptation of a nurse-led intervention trial to improve cardiovascular health at three large academic medical centers in the United States. Transcripts were analyzed using content analysis guided by principles drawn from grounded theory. Results Fifty-one individuals who had achieved viral suppression (

Objectives: Group A β-hemolytic Streptococcus (GAS), also known as Streptococcus pyogenes, is responsible for an annual 600 million cases of acute pharyngitis globally, with 92% of those infections occurring in low-resource settings. Further knowledge of the acute streptococcal pharyngitis burden in low-resource settings is essential if serious post-streptococcal complications – rheumatic fever (RF) and its long-term sequel rheumatic heart disease (RHD) – are to be prevented. Methods: Two studies were conducted in school-aged children (5–16 years): a cross-sectional study of streptococcal pharyngeal carriage followed by a prospective cohort study of streptococcal sore throat over 4 weeks from March to April 2017. Results: The cross-sectional study revealed an overall prevalence of GAS carriage of 15.9% (79/496, 95% confidence interval 12.8–19.5%). Among 532 children enrolled in the prospective cohort study, 358 (67%) reported 528 sore throats, with 221 (41.1%) experiencing at least one GAS-positive sore throat. The overall GAS-positive rate for sore throat was 41.8% (221/528). Conclusions: The GAS pharyngeal carriage rates seen in Uganda (15.9%, 95% confidence interval 12.8–19.5%) are higher than the most recent pooled results globally, at 12% (range 6–28%). Additionally, pilot data suggest a substantially higher percentage of sore throat that was GAS-positive (41.8%) compared to pooled global rates when active recruitment is employed. Keywords: Group A β-hemolytic Streptococcus, Uganda, Rheumatic fever, Rheumatic heart disease

Introduction Little is known about the epidemiology of coronary artery disease (CAD) in sub‐Saharan Africa, where the majority of people living with HIV (PLHIV) live. We assessed the association of HIV with CAD and explored relationships with monocyte activation in sex‐stratified analyses of older PLHIV and people without HIV (PWOH) in Uganda. Methods The Ugandan Study of HIV effects on the Myocardium and Atherosclerosis (mUTIMA) follows 100 PLHIV on antiretroviral therapy (ART) and 100 age‐ and sex‐matched PWOH controls in Kampala, Uganda; all >45 years of age with >1 cardiovascular disease risk factor. At the year 2 exam (2017–2019), 189 participants had available coronary calcium score and 165 had coronary CT angiography (CCTA) for this analysis. A subset of participants (n = 107) had both CCTA and fresh whole blood flow cytometry for monocyte phenotyping. Results Median age was 57.8 years and 63% were females. Overall, 88% had hypertension, 37% had diabetes and 4% were smokers. Atherosclerotic cardiovascular disease (ASCVD) risk was modestly higher for PWOH, but not statistically significant (median 10‐year ASCVD risk 7.2% for PLHIV vs. 8.6% for PWOH, p = 0.09). Median duration of ART was 12.7 years and 86% had suppressed viral load. Despite a high prevalence of risk factors, only 34/165 (21%, 95% CI 15–28%) had any coronary plaque. After adjustment for ASCVD risk score, HIV status was not associated with CAD (OR 0.55, 95% CI 0.23–1.30) but was associated with more severe CAD (segment severity score>3) among those with disease (OR 10.9, 95% CI 1.67–70.45). Females had a trend towards higher odds of CAD among PLHIV (OR 4.1, 95% CI 0.4–44.9), but a trend towards lower odds of CAD among PWOH (OR 0.30; 95% CI 0.07–1.3; HIV*sex interaction p = 0.019). CAD was positively correlated with classical monocytes (r = 0.3, p = 0.012) and negatively correlated with CX3CR1 expression (r = –0.31, p = 0.011) in PLHIV and negatively correlated with patrolling monocytes (r = –0.36, p = 0.031) and tissue factor expression (r = –0.39, p = 0.017) in PWOH. Conclusions Our results suggest that HIV may be associated more with severity rather than the presence of CAD in Uganda. Sex differences in the HIV effect suggest that tailored CAD prevention strategies may be required in this setting.

People living with HIV (PLHIV) experience high rates of fatigue which can be improved with physical activity. We examined the relationship between HIV infection, fatigue, cardiorespiratory fitness, physical activity, and myokines. Twenty HIV-positive and 20 HIV-uninfected adults completed an assessment of fatigue, a maximal cardiometabolic exercise test (VO(2) peak, VE/VO(2,) VO(2) at anaerobic threshold), serum measures of myokines (Il-15, IL-7, FGF-21, adiponectin), and wore an accelerometer for seven days. Measures were completed at baseline, 3 and 6 months. At baseline, PLHIV had more fatigue (4.7 ±2.6 vs 2.8 ±2.5, p=0.01) and higher peak VE/VCO(2) (33 ±5.5 vs. 30.2 ±2.5, p=0.06). Fifty percent of PLHIV engaged in at least one 10-minute bout of physical activity in the past week, compared to 65% of the control group. Over time, HIV infection and FGF-21 were associated with fatigue (p

Background There is geographical overlap between areas endemic for rheumatic heart disease (RHD) and those endemic for HIV. A recent pilot study demonstrated that children living with HIV might be at less risk for RHD development; however, the sample size was too small to make definitive conclusions. Our objective was to determine the prevalence of RHD among HIV-positive children in Uganda. Methods We conducted a prospective, cross-sectional study of HIV-positive children (5-15 years of age) receiving care at the Baylor Uganda HIV Clinic, Kampala, Uganda. A focused echocardiogram and chart review was performed. A sample size of 988 children was needed to provide 80% power to detect a difference in population prevalence between HIV-positive children and the general population, 2.97% [95% confidence interval (CI): 2.70-3.24%], based on previous reports. Results Screening echocardiography of 993 HIV-positive children found 15 individuals (1.5%; 95% CI: 0.88%-2.54%) with RHD. Of these 15, 2 were classified as definite RHD and 13 as borderline RHD. The majority of children had isolated mitral valve disease (93%). Children found to have RHD were older than those without RHD, 12 versus 10 years of age (P = 0.004). When separated based on geographic location, the prevalence of RHD among HIV-positive children from Kampala was 1.28% (95% CI: 0.63%-2.51%) compared with 2.1% (95% CI: 0.89%-4.89%) in those from outside Kampala. Conclusions Children living with HIV have a lower prevalence of RHD than the general pediatric population. Further studies are needed to explore this protective association.

Aim Human Immunodeficiency Virus (HIV) patients commonly experience dyspnea for which an immediate cause may not be always apparent. In this prospective cohort study of HIV patients with exercise limitation, we use cardiopulmonary exercise testing (CPET) coupled with exercise cardiovascular magnetic resonance (CMR) to elucidate etiologies of dyspnea. Methods and results Thirty-four HIV patients on antiretroviral therapy with dyspnea and exercise limitation (49.7 years, 65% male, mean absolute CD4 count 700) underwent comprehensive evaluation with combined rest and maximal exercise treadmill CMR and CPET. The overall mean oxygen consumption (VO2) peak was reduced at 23.2 ± 6.9 ml/kg/min with 20 patients (58.8% of overall cohort) achieving a respiratory exchange ratio > 1. The ventilatory efficiency (VE)/VCO2 slope was elevated at 36 ± 7.92, while ventilatory reserve (VE: maximal voluntary ventilation (MVV)) was within normal limits. The mean absolute right ventricular (RV) and left ventricular (LV) contractile reserves were preserved at 9.0% ± 11.2 and 9.4% ± 9.4, respectively. The average resting and post-exercise mean average pulmonary artery velocities were 12.2 ± 3.9 cm/s and 18.9 ± 8.3 respectively, which suggested lack of exercise induced pulmonary artery hypertension (PAH). LV but not RV delayed enhancement were identified in five patients. Correlation analysis found no relationship between peak VO2 measures of contractile RV or LV reserve, but LV and RV stroke volume correlated with PET CO2 (p = 0.02, p = 0.03). Conclusion Well treated patients with HIV appear to have conserved RV and LV function, contractile reserve and no evidence of exercise induced PAH. However, we found evidence of impaired ventilation suggesting a non-cardiopulmonary etiology for dyspnea.

Objective To examine the effect of a lifestyle behavior intervention (SystemCHANGE) on physical activity and diet quality among sedentary people living with HIV (PLHIV). All participants expressed a desire to improve lifestyle health behaviors. Methods One hundred and seven HIV+ adults were randomized to either the intervention (6, in-person, standardized group sessions focusing on improving lifestyle behaviors) or a control condition (general advice on AHA diet and exercise guidelines). All participants wore an ActiGraph accelerometer and completed 24-hour dietary recalls at baseline, 3, and 6 months. Generalized estimating equations were used to examine intervention effects. The primary activity outcome was time spent in moderate-to-vigorous physical activity, and the primary dietary outcome was Healthy Eating Index. Results Mean age was 53 years, 65% were male, and 86% African American. Approximately 90% attended at least half of the sessions and 60% attended 5 or more sessions. The intervention did not significantly improve our primary lifestyle behavior endpoints (P ≥ 0.05); however, intervention participants consumed fewer carbohydrates-primarily sugar-sweetened beverages-per day and lost 0.732 kg body weight compared with a 0.153 weight gain in the control group (P = 0.03). Conclusions Among sedentary PLHIV at high risk of cardiovascular disease, the SystemCHANGE intervention reduced daily carbohydrate intake and body weight, but did not increase physical activity or improve overall diet quality. Future work should identify fundamental personal, interpersonal, and contextual factors that will increase physical activity and improve overall diet quality among this population, and integrate these factors into tailored, lifestyle interventions for aging PLHIV.

Background Lifestyle physical activity (ie, moderate physical activity during routine daily activities most days of the week) may benefit human immunodeficiency virus (HIV)-positive adults who are at high risk for cardiovascular disease. Objective The aims of this study were to describe lifestyle physical activity patterns in HIV-positive adults and to examine the influence of lifestyle physical activity on markers of cardiovascular health. Our secondary objective was to compare these relationships between HIV-positive adults and well-matched HIV-uninfected adults. Methods A total of 109 HIV-positive adults and 20 control participants wore an ActiGraph accelerometer, completed a maximal graded cardiopulmonary exercise test, completed a coronary computed tomography, completed anthropomorphic measures, and had lipids and measures of insulin resistance measured from peripheral blood. Results Participants (N = 129) had a mean age of 52 ± 7.3 years, 64% were male (n = 82), and 88% were African American (n = 112). On average, HIV-positive participants engaged in 33 minutes of moderate-to-vigorous physical activity per day (interquartile range, 17-55 minutes) compared with 48 minutes in controls (interquartile range, 30-62 minutes, P = .05). Human immunodeficiency virus-positive adults had poor fitness (peak oxygen uptake [VO2], 16.8 ± 5.2 mL/min per kg; and a ventilatory efficiency, 33.1 [4.6]). A marker of HIV disease (current CD4+ T cell) was associated with reduced peak VO2 (r = -0.20, P Conclusion Human immunodeficiency virus-positive adults have poor physical activity patterns and diminished cardiovascular health. Future longitudinal studies should examine whether HIV infection blunts the beneficial effects of physical activity on cardiovascular health.

PURPOSE OF REVIEW The review aims to summarize the literature describing the clinical impact of cardiac fat depots in patients with HIV infection. RECENT FINDINGS People living with HIV (PLHIV) have accelerated rates of cardiovascular disease, and are prone to the development of ectopic fat deposition. Specifically, PLHIV have higher volumes of epicardial and intracardiac fat quantified by noninvasive imaging. Higher volumes of epicardial fat may be related to antiretroviral therapy duration and chronic inflammation, independently of other measures of body adiposity such as BMI. They have been associated with increased coronary artery calcium, myocardial perfusion defects, death, and myocardial infarction. The association with risk may be partly mediated through direct actions of cytokines and adipokines produced by the adipose tissue. Furthermore, HIV-infected patients have increased myocardial fat deposition that is also associated with antiretroviral therapy duration, and may be responsible for myocardial systolic and diastolic dysfunction. SUMMARY PLHIV have increased fat deposition surrounding and inside the heart that may serve as an important imaging marker of risk but may also directly mediate coronary artery disease and cardiac dysfunction. Although robust data of targeted therapies is lacking, some pharmacotherapies may be able to reduce cardiac fat volumes. In the meantime, as the evidence grows, physicians may consider intensifying preventive strategies and monitoring in patients with abnormal heart fat on noninvasive imaging.

Cardiac rehabilitation (CR) has proven morbidity and mortality benefits in cardiovascular disease, which directly correlates with exercise performance achieved. Many patients in CR exercise at sub-optimal levels, without obvious limitations. Occult lower-extremity peripheral artery disease (PAD) may be a determinant of diminished exercise capacity and reduced benefit obtained from traditional CR. In this prospective study of 150 consecutive patients enrolled in Phase II CR, we describe the prevalence of PAD, the utility of externally validated screening questionnaires, and the observed impact on CR outcomes. Abnormal ankle–brachial indices (ABI) (1.4) were observed in 19% of those studied. The Edinburgh Claudication Questionnaire was insensitive for detecting PAD by low ABI in this population, and the Walking Impairment Questionnaire and a modified Gardner protocol demonstrated a lack of typical symptoms with low levels of activity. Importantly, at completion of traditional CR, exercise improvement measured in metabolic equivalents (METs) was worse in those with a low ABI compared to those with a normal ABI (+1.39 vs +2.41 METs, p=0.002). In conclusion, PAD is common in patients in Phase II CR and often clinically occult. Screening based on standard questionnaires appears insensitive in this population, suggesting a need for a broad-based screening strategy with ABI measurements. In this study, undiagnosed PAD significantly attenuated improvements in exercise performance, which potentially has bearings on future clinical events.

To describe the relationship between a novel measurement of peri-arotic root fat and ultrasound measures of carotid artery remodeling.We studied 1492 consecutive subjects (mean age: 51.04 ± 8.97 years, 27% females) who underwent an annual cardiovascular risk survey in Taiwan. Peri-aortic root fat (PARF) was assessed by cardiac CT using three-dimensional (3D) volume assessment. Carotid artery morphology and remodeling were assessed by ultrasound. We explored the relationships between PARF volumes, cardiometabolic risk profiles and carotid morphology and remodeling.Mean PARF volume in current study was 20.8 ± 10.6 ml. PARF was positively correlated with measures of general adiposity, systemic inflammation, and several traditional cardiometabolic risk profiles (all p0.001) and successfully predicted metabolic syndrome (MetS) (AUROC: 0.75, 95%, confidence interval: 0.72-0.77). Higher PARF was independently associated with increased carotid artery intima-media thickness (IMT) (β-coef.: 0.08) and diameter (β-coef.: 0.08, both p0.05) after accounting for age, sex, BMI and other cardiovascular risk factors. The addition of PARF beyond metabolic syndrome components significantly provided incremental prediction value for abnormal IMT (ΔAUROC: 0.053, p = 0.0021).Peri-aortic root fat is associated with carotid IMT, even after adjustment for cardiometabolic risks, age and coronary atherosclerosis. Further research studies are warranted to identify the mediators of downstream pathophysiologic effects on carotid arteries by PARF and understand the mechanisms related to this correlation.

Objective HIV-infected participants are at a higher risk for cardiovascular disease (CVD). N-terminal pro-B-type natriuretic peptide (NT-proBNP) is a significant predictor of CVD in the general population and is associated with mortality in HIV. Design and methods The 96-week Stopping Atherosclerosis and Treating Unhealthy Bone with Rosuvastatin in HIV (SATURN-HIV) trial randomized 147 patients on stable antiretroviral therapy with low-density lipoprotein-cholesterol level lower than 130 mg/dl and without overt heart failure to 10 mg daily rosuvastatin or placebo. We measured NT-proBNP levels by enzyme-linked immunosorbent assay (ELISA). Baseline and changes in NT-proBNP were compared between groups. Spearman correlation was used to explore relationships between baseline NT-proBNP, inflammation, and CVD risk markers. Multivariable analyses were conducted to assess associations with NT-proBNP levels. Results Median age was 46 years, 80% were men, 69% were African American, and 46% were on protease inhibitors. At baseline, median (Q1, Q3) NT-proBNP was higher in the rosuvastatin group than placebo [41 (20, 66.5) versus 25 pg/ml (11, 56), P = 0.012)]. Baseline NT-proBNP correlated with bulb and common carotid artery intima-media thickness, coronary calcium score, interleukin 6, and cystatin C. After 96 weeks, median NT-proBNP decreased significantly in the rosuvastatin group versus placebo (-1.50 versus +4.50 pg/ml, P = 0.041). Within the rosuvastatin group, changes in NT-proBNP were negatively correlated with changes in insulin resistance and total limb fat. Conclusion Rosuvastatin reduces plasma NT-proBNP in HIV-infected participants on antiretroviral therapy. NT-proBNP correlated with several measures of CVD risk, independent of inflammation markers.

Objectives HIV-infected patients on antiretroviral therapy (ART) have an increased cardiovascular disease (CVD) risk as a result of heightened inflammation and immune activation, despite at times having normal lipids and few traditional risk factors. Biomarkers are needed to identify such patients before a clinical event. Lipoprotein-associated phospholipase A2 (Lp-PLA2) predicts CVD events in the general population. This study investigated the relationship between Lp-PLA2 and markers of CVD risk, systemic inflammation, immune activation, and coagulation in HIV infection. Methods One hundred subjects on stable ART with normal fasting low-density lipoprotein (LDL) cholesterol were enrolled in the study. Plasma Lp-PLA2 concentrations were measured by enzyme-linked immunosorbent assay (ELISA; > 200 ng/mL was considered high CVD risk). Subclinical atherosclerosis, endothelial function, inflammation, immune activation and fasting lipids were also evaluated. Results The median age of the patients was 47 years and 77% were male. Median (range) Lp-PLA2 was 209 (71–402) ng/mL. Fifty-seven per cent of patients had Lp-PLA2 concentrations > 200 ng/mL. Lp-PLA2 was positively correlated with soluble markers of inflammation or immune activation (tumour necrosis factor receptor-II, intercellular and vascular cellular adhesion molecules, and CD14; all R = 0.3; P

Background Human Immunodeficiency Infection (HIV) is associated with increased risk for heart failure (HF). Outcomes of HF in people living with HIV (PLHIV) are unknown. We sought to identify the risk of HF readmissions (30 and 90 days) among PLHIV vs uninfected controls admitted with HF. Methods Using the 2016 national readmission database, we identified all patients (≥ 18 years) who were discharged alive with a primary diagnosis of HF (ICD10 I50.xx) with or without secondary diagnosis of HIV (ICD 10 Z21, B20, O98.7, or B97.35). Propensity score matching (PSM) was used to match PLHIV with controls (1:1) based on 45 patient characteristics (demographics, hospitalization characteristics, and comorbidities). Cox regression models were used to compare rates of HF readmission (primary ICD10 I50.xx) within 30 and 90 days after discharge from index HF hospitalization. Results A total of 312,264 patients with HF were identified, of whom 1,112 (0.4%) had HIV. After PSM, 1,112 PLHIV were matched with 1,112 uninfected controls. The standard mean difference for each variable was less than 10% post-matching. Overall, HF readmission rates were 11.2% and 19.2% at 30 and 90 days, respectively. The two groups (PLHIV and controls) were not different statistically with respect to all 45 covariates. Compared with controls, PLHIV had higher risk of HF readmission within 30 days (HR 1.45, 95% CI: 1.13-1.87, P=0.004) and 90 days (HR 1.41, 95% CI 1.16-1.71, P Conclusions In this propensity-matched national cohort of patients admitted with HF, patients with HIV appear to have increased risk of HF readmissions compared with uninfected controls at 30 days and 90 days.

HIV-infection is characterized by chronic immune activation that persists despite effective antiretroviral therapy (ART) and is associated with elevated cardiovascular risk. Whether specific perivascular fat depots are associated with inflammation in HIV is unknown.In a cross-sectional study, epicardial (EAT) and thoracic periaortic (TAT) adipose tissue volumes were measured by computed tomography in 100 HIV-infected adults, on stable ART, with LDL-cholesterol ≤130 mg/dL and evidence of heightened T-cell activation (CD8+CD38+HLA-DR+ ≥19%) or increased inflammation (high sensitivity C-reactive protein ≥2 mg/L).Overall, 77% were males and 70% African American. Mean (standard deviation) age and body mass index were 47 (10) years and 28 (6.4) kg/m(2), respectively. All subjects had HIV-1 RNA1000 copies/mL with mean (standard deviation) CD4+ T cell count of 665 (280) cells/μL; 50% were on a protease inhibitor. EAT and TAT were correlated with each other (r = 0.766, p0.0001). Both were associated with metabolic syndrome, atherogenic lipid profile, insulin resistance, total and central body fat, serum biomarkers of inflammation, and soluble CD163, but not with cellular immune activation markers. In multivariable models that adjusted for age, sex, and other measures of adiposity, both perivascular fat depots were independently associated with the presence of coronary calcium.Perivascular fat is associated with soluble CD163, biomarkers of inflammation, insulin resistance, and subclinical atherosclerosis in this population of virologically suppressed HIV-infected patients on ART. The association of perivascular fat with coronary artery calcification appears to be independent of other measures of adiposity.

OBJECTIVE To explore the relationships between lymphocyte and monocyte activation, inflammation, and subclinical vascular disease among HIV-1 infected patients on antiretroviral therapy.

Coenzyme Q10 (CoQ10) deficiency has been associated with statin-induced myopathy, and supplementation with CoQ10 may reduce inflammation markers. The effects of statins on CoQ10 and its anti-inflammatory properties have not been investigated in HIV-positive patients.The objectives of this study were to examine the effect of rosuvastatin on CoQ10 and CoQ10/LDL ratio over 24-week SATURN-HIV trial, explore the associations between CoQ10 levels and markers of vascular disease, inflammation, and immune activation, and assess whether changes in CoQ10 affected the anti-inflammatory effects of statin therapy or were associated with myalgia symptoms.This was a secondary analysis of the SATURN-HIV trial, a 96-week randomized clinical trial of 10 mg daily rosuvastatin vs. placebo in HIV-infected patients on antiretroviral therapy. We assessed the statin treatment effect on CoQ10 levels and CoQ10/LDL ratios and whether changes in these markers were related to myalgias. Relationships between CoQ10, subclinical vascular disease, and biomarkers of inflammation and immune activation were explored using Spearman correlations and multivariable regression models.Overall, 147 patients were included. Median age was 46 years; 78% were male and 68% African American. At baseline, CoQ10 levels and CoQ10/LDL ratio were modestly correlated with markers of HIV disease, immune activation, and carotid distensibility. After 24 weeks of statin therapy, CoQ10 levels decreased (p = 0.002 for between group difference) and CoQ10/LDL ratio increased (p = 0.036). In the statin treatment arm, we did not find evidence of a relationship between changes in CoQ10 or CoQ10/LDL ration and changes in markers of inflammation or immune activation. There was a borderline statistically significant association between changes in CoQ10 and myalgia symptoms [OR 4.0 per 0.1 mg/L decrease in CoQ10, p = 0.07].Twenty-four weeks of 10 mg daily rosuvastatin decreases CoQ10 concentration and increases CoQ10/LDL ratio in HIV-infected patients on antiretroviral therapy.

Objectives Enhanced inflammation is evident in HIV infection, even with virological suppression. Outside HIV infection, studies show an independent association between higher total bilirubin and better endothelial function as well as a lower prevalence of coronary heart disease, possibly as a consequence of the anti-inflammatory and antioxidant effect of bilirubin. The aim of this study was to determine whether such an association exists in HIV-infected individuals. Methods A cross-sectional study was performed in HIV-1-infected adults on stable antiretroviral therapy (ART) to determine if a relationship exists between total bilirubin and endothelial function [flow-mediated dilation (FMD) of the brachial artery], inflammation [interleukin-6 (IL-6), soluble tumour necrosis factor receptors, C-reactive protein, and adhesion molecules], coagulation markers (fibrinogen and D-dimer) and oxidative stress (F 2-isoprostanes). Endpoints were compared based on total bilirubin levels and atazanavir status using distributionally appropriate, two-sample tests. Correlation coefficients were determined between total bilirubin and endpoints. Linear regression was used to model the relationship between total bilirubin (and atazanavir status) and FMD. Results A total of 98 adults were included in the study. Total bilirubin was higher in the atazanavir group when compared to the non-atazanavir group [median (interquartile range) 1.8 (1.1–2.6) vs. 0.6 (0.4–1.4) mg/dL; P

Dyspnea and exercise intolerance are common symptoms among patients with HIV. Cardiac magnetic resonance imaging (CMR) has emerged as a versatile tool in the evaluation of cardiovascular disorders including pulmonary arterial hypertension (PAH). We sought to determine the utility of a novel

BACKGROUND Among patients with HIV infection, changes in the kidney filtration marker cystatin C after initiation of antiretroviral therapy (ART) may be related to changes in body composition or biomarkers of inflammation. METHODS ACTG A5224s was a substudy of A5202, which randomly assigned ART-naive HIV-infected subjects to blinded abacavir/lamivudine (ABC/3TC) or tenofovir/emtricitabine (TDF/FTC) with open-label efavirenz (EFV) or ritonavir-boosted atazanavir. This analysis explored changes in cystatin C from 0 to 96 weeks. RESULTS Of the 269 subjects, 85% were male and 66% white non-Hispanics; baseline mean CD4 count was 236 cells per cubic millimeter and cystatin C was 0.89 mg/L. Cystatin C decreased significantly within each arm; however, ritonavir-boosted atazanavir attenuated the beneficial effects of ART on cystatin C compared to EFV. Compared to ABC/3TC, TDF/FTC led to a marginally significant attenuation for percent change analyses only. Higher baseline body mass index and HIV RNA were associated with larger reductions in cystatin C in multivariable models. At baseline, cystatin C was positively correlated with high-sensitivity C-reactive protein (Spearman r = 0.25), interleukin 6 (r = 0.34), soluble intercellular adhesion molecule (r = 0.36), soluble vascular cell adhesion molecule (r = 0.54), tumor necrosis factor α (r = 0.57), and soluble TNF-α receptor I (r = 0.70, all P < 0.001). Reductions in cystatin C from 0 to 96 weeks correlated with reductions in all inflammatory biomarkers (r = 0.39-0.58, P < 0.001) except for high-sensitivity C-reactive protein (r = 0.01, P = 0.89) and IL-6 (r = 0.08, P = 0.24). CONCLUSIONS The beneficial effect of ART on cystatin C concentrations is attenuated by boosted ATV when compared to EFV. Reductions in cystatin C after ART are associated with reductions in systemic inflammation.

Spontaneous coronary artery dissection (SCAD) is a rare cause of acute coronary syndrome in pregnant women. Delay in the diagnosis might lead to substantial maternal and fetal morbidity and mortality. Although there have been reports of SCAD in pregnancy, to our knowledge, there have been no reports of maternal and fetal hemodynamic compromise related to SCAD leading to emergent delivery of fetus in the cardiac catheterization laboratory.

The expansion of antiretroviral therapy (ART) in resource-limited settings (RLS) has dramatically changed the face of the AIDS epidemic in Sub-Saharan Africa over the past decade 1. The progress in HIV/AIDS care is in large part due to successful bilateral and multilateral collaborations of governments and non-governmental AIDS organizations. In Uganda, for example, with funding support from the National Institutes of Health (NIH) and the President's Emergency Plan for AIDS Relief, Case Western Reserve University (CWRU) and others have partnered with Ugandan institutions to develop a comprehensive HIV/AIDS infrastructure. Because of this concerted effort, the country has seen a fall in HIV prevalence from a peak of 25-30% in major urban areas to now less than 7% nationally, and nearly half of those who qualify for treatment are currently receiving it 2. These successes, however, bring new challenges. As HIV has now become a manageable chronic disease, the infected population has aged, and the higher prevalence of co-morbidities such as cardiovascular disease is increasingly recognized. The specter of a dual epidemic of HIV/AIDS and non-communicable disease threatens to place significant demands on these fragile healthcare systems 3. In addition to the higher risk of ischemic heart disease observed in the developed and developing world, the burden of endemic cardiovascular disease such as tuberculous pericarditis and rheumatic heart disease among persons living with HIV in RLS is unknown. Recognizing this emerging need, Makerere University School of Medicine, Mulago Hospital, and the Uganda Heart Institute have partnered with CWRU to extend collaboration beyond HIV/AIDS to cardiovascular disease (CVD), neurology, and oncology. Funded in part by the NIH/Fogarty International Medical Education Partnership Initiative (MEPI), the cardiology collaboration aims to provide contextually appropriate training of cardiovascular specialists and conduct research on CVD risk factors, including the impact of HIV/AIDS. As part of the MEPI collaboration, a team of cardiologists from CWRU traveled to Kampala, Uganda in August 2012 to perform procedures in the newly opened cardiac catheterization laboratory at the Uganda Heart Institute (UHI), Mulago Hospital, including the country's first percutaneous mitral balloon valvuloplasties (PMBV) for rheumatic mitral stenosis (Figure 1A and B). Although rarely seen in the developed world, rheumatic heart disease (RHD) remains a leading cause of cardiovascular morbidity and mortality in RLS, affecting over 1 million children in Sub-Saharan Africa alone 4. RHD is a chronic complication of rheumatic fever, an auto-immune reaction to antecedent Group A streptococcus pharyngitis that causes varying degrees of carditis 5. Significant valvular regurgitation or stenosis may occur during the initial insult or after repeated damage to the valve from recurrent bouts of acute rheumatic fever 5. Congestive heart failure then develops insidiously and may lead to death in the 2nd to 5th decades of life if the valve is not repaired. The current treatment of choice in developed countries for rheumatic mitral valve stenosis without significant regurgitation is percutaneous balloon valvuloplasty6. Figure 1 A) Members of the Case Western Reserve University team with the Uganda Heart Institute physicians and cardiac catheterization lab staff. The new facility at the Uganda Heart Institute was completed in February of 2012. B) Dr. Marco Costa and Dr. Dan Simon ... The first patient to benefit from this minimally-invasive procedure in Uganda was HIV-infected. In a country with a high prevalence of HIV/AIDS, it may be coincidence that this patient happened to be HIV-infected. Nonetheless, several questions arise regarding the impact of HIV on RHD (and other endemic non-communicable disease) in the country. Are perinatally HIV-infected children more or less likely than their uninfected peers to acquire acute rheumatic fever? What is the role of chronic inflammation and immune activation associated with HIV on outcomes among children with RHD? In patients with AIDS, does the CD4+ lymphopenia associated with acute rheumatic fever lead to further immunosuppression and increased susceptibility to opportunistic infections? Is someone with subclinical RHD acquired in childhood more or less likely to develop progressive disease if they become HIV-infected as an adult? Among patients colonized with Group A streptococci who are started on ART therapy, can subclinical rheumatic carditis develop within the spectrum of immune reconstitution inflammatory syndromes (IRIS)? Although RHD is rare in the developed world, other rheumatic/immunologic complications of HIV/AIDS are not uncommon. The spectrum of disease has changed since the introduction of combination ART in the mid-1990's 8,9. Autoimmunity appears to be increased in chronic HIV-infection, and molecular mimicry may be an important mechanism 10. For example, in a recent study from South Africa, anti-cyclic citrullinated peptide (anti-CCP) antibody titers were increased in advanced HIV-infection compared to controls and decreased after initiation of antiretroviral therapy 11. In this context, the anti-CCP antibodies lacked the typically high specificity for rheumatoid arthritis. In some cases, inflammatory arthritis such as psoriatic arthritis 12 or rheumatoid arthritis 13 may be the initial presentation of HIV/AIDS. On the other hand, advanced immunosuppression may suppress the clinical manifestations of pre-existing auto-immune conditions such as inflammatory bowel disease, systemic lupus erythematosis and rheumatoid arthritis 14. Despite this literature, little is known about the interaction of HIV with rheumatic fever and RHD. Some studies have demonstrated an increased risk for group A streptococcal infection with underlying HIV infection15; however, to our knowledge, only one case of acute rheumatic fever in an AIDS patient has been reported previously 16. The CWRU team continues to return quarterly to Uganda as part of a comprehensive skills transfer program that also includes training for Ugandan physicians in Cleveland, Ohio. In addition, CWRU has partnered with the UHI and the Joint Clinical Research Centre (a center in existence in Uganda for care and research in HIV/AIDS) to focus specifically on RHD through an innovative foundation-funded project. This program will utilize an existing network of HIV/AIDS infrastructure to create community-based RHD treatment centers of excellence. If successful, this program may serve as a model for leveraging HIV/AIDS resources for the treatment of non-communicable diseases among both HIV-infected and uninfected patients in RLS. We are now at a crossroads. An opportunity exists to build upon the dramatic improvements in healthcare infrastructure that HIV/AIDS investment has brought over the past decade. To extend the benefits of the ART rollout to the treatment of non-AIDS co-morbidities such as RHD will require a coordinated research effort and capital investment in health systems, particularly in human resources. Multilateral collaborations in medical specialties beyond infectious diseases that share the tripartite mission of research, education, and clinical care such as the one described in this report will be needed to move to the next level of HIV/AIDS treatment in Sub-Saharan Africa and other RLS.