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To synthesize current evidence on the impact of cardiovascular disease among women living with HIV (WLWH) with a particular focus on disease prevalence, mechanisms and prevention.HIV-related cardiovascular disease risk is 1.5-fold to 2-fold higher for women than for men. Mechanisms of enhanced risk are multifactorial and include reinforcing pathways between traditional risk factors, metabolic dysregulation, early reproductive aging and chronic immune activation. These pathways influence both the presentation of overt syndromes of myocardial infarction, stroke and heart failure, as well as subclinical disease, such as microvascular dysfunction and cardiac fibrosis. Cardiovascular disease, therefore, remains a consistent threat to healthy aging among WLWH.Although no specific prevention strategies exist, patient-centered risk mitigation approaches that are adaptable to the needs of aging individuals are essential to combat disparities in cardiovascular outcomes among WLWH. Further research into the optimal prevention approach for CVD among WLWH, particularly for women living in under-resourced health systems, is needed.

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.

Background Prospective investigations on the risk of cardiovascular disease among youth with perinatally acquired human immunodeficiency virus (PHIV) in sub-Saharan Africa are lacking. Methods A prospective observational cohort study was performed in 101 youth (aged 10–18 years) with PHIV and 97 who were human immunodeficiency virus (HIV) uninfected (HIV−), from 2017 to 2021 at the Joint Clinical Research Center in Uganda. Participants with PHIV were receiving antiretroviral therapy (ART) and had HIV-1 RNA levels ≤400 copies/mL. The common carotid artery intima-media thickness (IMT) and pulse wave velocity (PWV) were evaluated at baseline and at 96 weeks. Groups were compared using unpaired t-test, and potential predictors of IMT and PWV were assessed using quantile regression. Results Of the 198 participants recruited at baseline, 168 (89 with PHIV, 79 HIV−) had measurements at 96 weeks. The median age (interquartile range) age was 13 (11–15) years; 52% were female, and 85% had viral loads Conclusions In healthy Ugandan youth with PHIV, virally suppressed by ART, the common carotid artery IMT did not progress over 2 years. Prolonged and early ART may prevent progression of subclinical vascular disease, while prolonged use of abacavir may increase it.

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.

Background Underrepresented racial and ethnic groups (UREGs) with HIV have a higher risk of cardiovascular disease (CVD) compared with the general population. Referral to a cardiovascular specialist improves CVD risk factor management in high-risk individuals. However, patient and provider factors impacting the likelihood of UREGs with HIV to have an encounter with a cardiologist are unknown. Methods We evaluated a cohort of UREGs with HIV and borderline CVD risk (10-year risk ≥ 5% by the pooled cohort equations or ≥ 7.5% by Framingham risk score). Participants received HIV-related care from 2014–2020 at four academic medical centers in the United States (U.S.). Adjusted Cox proportional hazards regression was used to estimate the association of patient and provider characteristics with time to first ambulatory cardiology encounter. Results A total of 2,039 people with HIV (PWH) and borderline CVD risk were identified. The median age was 45 years (IQR: 36–50); 52% were female; and 94% were Black. Of these participants, 283 (14%) had an ambulatory visit with a cardiologist (17% of women vs. 11% of men, p Conclusion In UREGs with HIV and borderline CVD risk, the strongest determinants of a cardiology encounter were diagnosed CVD, insurance type, and urban residence. Future research is needed to determine the extent to which these encounters impact CVD care practices and outcomes in this population. Trial Registration ClinicalTrials.gov Identifier: NCT04025125.

Background People with human immunodeficiency virus (PWH) are at increased risk for comorbidities, and plasma interleukin 6 (IL-6) levels are among the most robust predictors of these outcomes. Tocilizumab (TCZ) blocks the receptor for IL-6, inhibiting functions of this cytokine. Methods This was a 40-week, placebo-controlled, crossover trial (NCT02049437) where PWH on stable antiretroviral therapy (ART) were randomized to receive 3 monthly doses of TCZ or matching placebo intravenously. Following a 10-week treatment period and a 12-week washout, participants were switched to the opposite treatment. The primary endpoints were safety and posttreatment levels of C-reactive protein (CRP) and CD4+ T-cell cycling. Secondary endpoints included changes in inflammatory indices and lipid levels. Results There were 9 treatment-related toxicities of grade 2 or greater during TCZ administration (mostly neutropenia) and 2 during placebo administration. Thirty-one of 34 participants completed the study and were included in a modified intent-to-treat analysis. TCZ reduced levels of CRP (median decrease, 1819.9 ng/mL, P < .0001; effect size, 0.87) and reduced inflammatory markers in PWH, including D-dimer, soluble CD14, and tumor necrosis factor receptors. T-cell cycling tended to decrease in all maturation subsets after TCZ administration, but was only significant among naive CD4 T cells. Lipid levels, including lipid classes that have been related to cardiovascular disease risk, increased during TCZ treatment. Conclusions TCZ is safe and decreases inflammation in PWH; IL-6 is a key driver of the inflammatory environment that predicts morbidity and mortality in ART-treated PWH. The clinical significance of lipid elevations during TCZ treatment requires further study.

Statins are cholesterol-lowering drugs commonly used among people with HIV, associated with an increased risk of myopathies. Considering that cardiovascular disease, statin therapy, and sarcopenia are independently prevalent in people with HIV, clarity on the potential benefits or harms of statin therapy on muscle health is useful to provide insight into ways to maximize skeletal muscle health and minimize CVD risk in this population. We aimed to study the effects of statin therapy on strength, muscle mass, and physical function parameters in people with HIV. This was a pilot cross-sectional study. People with HIV on continuous statin therapy (n = 52) were paired 1:1 according to age (people with HIV 53.9 ± 8.2 and people with HIV on statins 53.9 ± 8.4 years), sex, body mass index (Body mass index, people with HIV 28.6 ± 5.3 and people with HIV on statins 28.8 ± 6.3 kg/m2), and race with people with HIV not using statin (n = 52). Participants were evaluated for muscle strength (i.e. handgrip strength), lean and fat body mass (using bioelectric impedance analysis), and physical function (i.e. Short Physical Performance Battery—SPPB). Isokinetic strength and appendicular lean mass (using dual-energy X-ray absorptiometry), more accurate strength and body composition measures, were determined in 38% of the participants. Overall, statin usage does not exacerbated loss of muscle strength (32.2 ± 11.5 vs. 30.3 ± 9.6 kg, p > 0.05) muscle mass (7.6 ± 1.8 vs. 7.7 ± 1.1 kg/m2, p > 0.05), and impaired physical performance (10.1 ± 1.8 vs. 9.7 ± 2.1 points, p > 0.05) of PLWH. When analyzed by sex, men living with HIV on statins usage presented higher appendicular muscle mass (28.4 ± 3.1 vs. 26.2 ± 4.9 kg, p p p

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: Multiple studies have reported a high burden of hypertension in sub-Saharan Africa, but none have examined early stage hypertension. We examined contemporary prevalence of diagnosed, treated, and controlled stage I (130–139/80–89 mm Hg) and II ( ≥ 140/90 mm Hg) hypertension in the general population of sub-Saharan Africa. Methods: We analyzed World Health Organization STEPwise Approach to Noncommunicable Disease Risk Factor Surveillance surveys from 17 sub-Saharan Africa countries including 85 371 respondents representing 85 million individuals from 2010 to 2017. We extracted demographic variables, blood pressure, self-reported hypertension diagnosis/awareness, and treatment status to estimate prevalence of stage I and II hypertension and treatment by country. We examined diagnosis and treatment trends by national sociodemographic index, a marker of development. Results: Stage I hypertension prevalence (regardless of diagnosis/treatment) was >25% in 13 of 17 countries, highest in Sudan (35.3% [95% CI, 33.7%–37.0%]), and lowest in Eritrea (20.2% [18.8%–21.6%]). Combined stages I and II hypertension prevalence was >50% in 13 countries; P =0.008), although there was substantial variation between countries even at similar levels of development. Conclusions: Hypertension is common in sub-Saharan Africa but rates of diagnosis, treatment, and control markedly low. There is a large population with early stage hypertension that may benefit from behavioral counseling to prevent progression. Our analyses suggest that success in population hypertension care may be achieved independently of socioeconomic development, highlighting a need for policymakers to identify best practices in those countries that outperform similar or more developed countries.

IntroductionThe prevalence of cardiovascular disease (CVD) is rising in Sub-Saharan Africa, but it is not known whether current risk assessment tools predict coronary atherosclerosis in the region. Furthermore, sex-specific performance and interaction with HIV serostatus has not been well studied.MethodsThis cross-sectional study compared ASCVD risk scores and detectable coronary artery calcium (CAC>0) by sex in Kampala, Uganda (n=200). The cohort was enriched for persons living with HIV, and all participants had at least one CVD risk factor. We fit log binomial regression models and constructed ROC curves to assess the correlation between ASCVD scores and CAC>0.ResultsThe mean age was 56. 62% were female and 50% of both men and women were living with HIV. The median 10-year ASCVD risk score was significantly higher in men (11.0%, IQR 7.6-19.4%) than in women (5.1%, IQR 3.2-8.7%), although the prevalence of CAC>0 was similar (8.1 vs 10.5%, p=0.63). Each 10% increase in ASCVD risk was associated with increased risk of CAC>0 in men (PR 1.59, 95% CI 1.00-2.55, p=0.05) but not women (PR 1.15, 95% CI 0.44-3.00, p=0.77). ROC curves demonstrated an AUC of 0.57 for women vs 0.70 for men. Adjustment for HIV serostatus improved the predictive value of ASCVD in women only (AUC 0.78, p=0.02).ConclusionsASCVD risk score did not correlate with the presence of CAC in women. When HIV status was added to the ASCVD risk score, correlation with CAC was improved in women but not in men.

Background Rheumatic heart disease (RHD) affects 41 million people worldwide, mostly in low- and middle-income countries, where it is co-endemic with human immunodeficiency virus (HIV). HIV is also a chronic inflammatory disorder associated with cardiovascular complications, yet the epidemiology of patients affected by both diseases is poorly understood. Methods Utilizing the Uganda National RHD Registry, we described the echocardiographic findings, clinical characteristics, medication prescription rates, and outcomes of all 73 people carrying concurrent diagnoses of HIV and RHD between 2009 and 2018. These individuals were compared to an age- and sex-matched cohort of 365 subjects with RHD only. Results The median age of the HIV-RHD group was 36 years (interquartile range [IQR] 15), and 86% were women. The HIV-RHD cohort had higher rates of prior stroke/transient ischemic attack (12% vs 5%, P = .02) than the RHD-only group, with this association persisting following multivariable adjustment (odds ratio [OR] 3.08, P = .03). Prevalence of other comorbidities, echocardiographic findings, prophylactic penicillin prescription rates, retention in clinical care, and mortality were similar between the 2 groups. Conclusions Patients living with RHD and HIV in Uganda are a relatively young, predominantly female group. Although RHD-HIV comorbid individuals have higher rates of stroke, their similar all-cause mortality and RHD care quality metrics (such as retention in care) compared to those with RHD alone suggest rheumatic heart disease defines their clinical outcome more than HIV does. We believe this study to be one of the first reports of the epidemiologic profile and longitudinal outcomes of patients who carry diagnoses of both conditions.

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.

People living with HIV (PLWH) are at increased risk for cardiovascular disease. Physical activity, exercise, and controlled diet can mitigate this risk, yet these behaviors are understudied in sub-Saharan Africa. Our objective was to describe and compare the meaning, value, and patterns of physical activity, exercise, and diet among PLWH and older adults without HIV in Uganda. This mixed methods, observational study included 30 adult PLWH and 29 adults without HIV who (a) wore an accelerometer to measure physical activity; (b) had weight, height, and waist and hip circumference measured; (c) completed physical fitness measures; and (d) used digital cameras to record photographs and videos of their typical diet and physical activities. Participants were approximately 58 years old and 68% female. Approximately 20% of PLWH and 40% of adults without HIV met physical activity guidelines (p > .05). Qualitative themes included engaging in a variety of exercise, structural barriers to exercising, and typical meals. Older adults in Uganda have low levels of physical activity and homogenous diets, increasing their risk for cardiovascular disease.

OBJECTIVES To characterize monocyte subsets and activation in persons living with HIV (PLWH) with tuberculosis coinfection. DESIGN Cross-sectional study within a cohort of PLWH and HIV-uninfected participants at the Joint Clinical Research Centre in Kampala, Uganda. METHODS Participants were at least 45 years old with at least one cardiovascular risk factor. PLWH had an HIV viral load 1000 copies/ml or less on stable antiretroviral therapy prior to cohort entry. QuantiFERON-TB testing was performed to define latent tuberculosis infection (LTBI). Prior active TB was defined by self-report and verified by medical records. Blood was stained with monocyte subset markers (CD14+, CD16), CD62p, CD69, CX3CR1, HLA-DR, and tissue factor, and examined with flow cytometry. RESULTS One hundred and twenty-five participants (83 PLWH and 42 without HIV) were included. Median CD4+ count was 582 cells/μl in PLWH. PLWH had a higher frequency of total monocytes (4.3% vs. 3.2%; P

ObjectiveDespite substantial variation of streptococcal antibody titres among global populations, there is no data on normal values in sub-Saharan Africa. The objective of this study was to establish normal values for antistreptolysin O (ASO) and antideoxyribonuclease B (ADB) antibodies in Uganda.DesignThis was an observational cross-sectional study.SettingThis study was conducted at Mulago National Referral Hospital, which is located in the capital city, Kampala, and includes the Uganda Heart Institute.PatientsParticipants (aged 0–50 years) were recruited. Of 428 participants, 22 were excluded from analysis, and 183 (44.4%) of the remaining were children aged 5–15 years.Main outcome measuresASO was measured in-country by nephelometric technique. ADB samples were sent to Australia (PathWest) for analysis by enzyme inhibition assay: 80% upper limit values were established.ResultsThe median ASO titre in this age group was 220 IU/mL, with the 80th percentile value of 389 IU/mL. The median ADB titre in this age group was 375 IU/mL, with the 80th percentile value of 568 IU/mL.ConclusionsThe estimated Ugandan paediatric population standardised 80% upper-limit-of-normal ASO and ADB titres is higher than many global populations. Appropriateness of using population-specific antibody cutoffs is yet to be determined and has important implications for the sensitivity and specificity of rheumatic fever diagnosis.

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

Despite developments to improve health in the United States, racial and ethnic disparities persist. These disparities have profound impact on the wellbeing of historically marginalized racial and ethnic groups. This narrative review explores disparities by race in people living with cardiovascular disease (CVD) and the Human Immunodeficiency Virus (HIV). We discuss selected common social determinants of health for both of these conditions which include; regional historical policies, incarceration, and neighborhood effects. Data on racial disparities for persons living with comorbid HIV and CVD are lacking. We found few published articles (n = 7) describing racial disparities for persons living with both comorbid HIV and CVD. Efforts to reduce CVD morbidity in historically marginalized racial and ethnic groups with HIV must address participation in clinical research, social determinants of health and translation of research into clinical practice.

Antiretroviral therapy (ART) prevented premature mortality and improved the quality of life among people living with the human immunodeficiency virus (PLWH), such that now more than half of PLWH in the United States are 50 years of age and older. Increased longevity among PLWH has resulted in a significant rise in chronic, comorbid diseases. However, the implementation of guideline-based interventions for preventing, treating, and managing such age-related, chronic conditions among the HIV population is lacking. The PRECluDE consortium supported by the Center for Translation Research and Implementation Science at the National Heart, Lung, and Blood Institute catalyzes implementation research on proven-effective interventions for co-occurring heart, lung, blood, and sleep diseases and conditions among PLWH. These collaborative research studies use novel implementation frameworks with HIV, mental health, cardiovascular, and pulmonary care to advance comprehensive HIV and chronic disease healthcare in a variety of settings and among diverse populations.

Stakeholder-informed strategies addressing cardiovascular disease (CVD) burden among people living with HIV (PWH) are needed within healthcare settings. This study provides an assessment of how human-centered design (HCD) guided the adaptation of a nurse-led intervention to reduce CVD risk among PWH. Using a HCD approach, research staff guided two multidisciplinary “design teams” in Ohio and North Carolina, with each having five HCD meetings. We conducted acceptability and feasibility testing. Six core recommendations were produced by two design teams of key stakeholders and further developed after the acceptability and feasibility testing to produce a final list of 14 actionable areas of adaptation. Acceptability and feasibility testing revealed areas for adaptation, e.g. patient preferences for communication and the benefit of additional staff to support patient follow-up. In conclusion, along with acceptability and feasibility testing, HCD led to the production of 14 key recommendations to enhance the effectiveness and scalability of an integrated HIV/CVD intervention.

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.

Introduction: Sub-Saharan Africa (SSA) is disproportionately impacted by HIV and HIV-related atherosclerotic cardiovascular disease (ASCVD). Since physical activity may prevent ASCVD events, it is important to understand how physical activity and inactivity relate to ASCVD risk among men and women with and without HIV in SSA. Methods: One hundred people with HIV (PWH) and 100 people without HIV (PWOH) matched by age and sex were enrolled into this observational study in Kampala, Uganda. Physical activity was objectively measured by actigraphy for 7 days, including steps per day, light activity time, moderate-to-vigorous activity time and sedentary time. ASCVD risk was assessed using the pooled-cohort equations. Coronary artery disease was quantified by cardiac computed tomography angiography. Multivariable linear and logistic regression models were used to determine the relationship between physical activity, ASCVD risk, and subclinical coronary disease. Results: Median age was 57 years; 63% were female and median ASCVD risk score was 7.9%. All PWH were on antiretroviral therapy and 86% had undetectable HIV viral load. Physical activity patterns were similar by HIV status (all p>0.2). Compared to males, females took more steps per day ( p =0.001) and engaged in more light activity time ( p p 0.8). After adjusting for moderate-to-vigorous activity time, sedentary time remained positively associated with ASCVD risk (standardized β=0.334, p p =0.028) but not males (p=0.194) and in PWOH (β=0.430, p=0.001) but not PWH (p=0.380). Sedentary time was associated with the presence of coronary artery disease plaque, even after adjustment for ASCVD risk score (adjusted OR= 1.039 per hour of sedentary time, p =0.018). Conclusions: Sedentary time is strongly associated with atherosclerotic cardiovascular disease risk in Uganda, particularly among females, but less so among PWH. Future studies should consider the influence of sex and HIV status while developing targeted strategies to improve physical activity and reduce sedentary time.

Women with HIV may experience higher rates of non-AIDS comorbidities compared to men with HIV, but the underlying mechanisms are not well understood. We investigated sex-related differences in the effects of HIV on monocyte phenotypes within the Ugandan Study of HIV effects on the Myocardium and Atherosclerosis (mUTIMA). Of 133 participants who provided blood for flow cytometry assays, 86 (65%) were women and 91 (68%) were persons living with HIV (PLWH) on antiretroviral therapy. The median age was 57 (interquartile range, 52–63) years. PLWH exhibited a lower proportion of circulating CD14+CD16- classical monocytes (66.3% vs. 75.1%, p &lt, 0.001), and higher proportion of CD14+CD16+ inflammatory monocytes (17% vs. 11.7%, p = 0.005) compared to HIV-uninfected participants. PLWH had an increased expression of the chemokine receptor CX3CR1 in total monocytes (CX3CR1+ monocytes, 24.5% vs. 4.7%, 0.001) and monocyte subsets. These findings were generally similar when analyzed by sex, with no significant interactions between sex and HIV status in adjusted models. Our data show that the inflammatory monocyte subset is expanded and monocyte CX3CR1 chemokine receptor expression is enhanced among PLWH, regardless of sex. Whether these parameters differentially affect risk for non-AIDS comorbidities and clinical outcomes in women with HIV requires additional investigation.

ObjectivesTo examine the relationship between pericardial fat (PCF) and cardiac structure and function among HIV-infected patients in the sub-Saharan African country of Uganda. People living with HIV (PLHIV) have altered fat distribution and an elevated risk for heart failure. Whether altered quantity and radiodensity of fat surrounding the heart relates to cardiac dysfunction in this population is unknown.MethodsOne hundred HIV-positive Ugandans on antiretroviral therapy were compared with 100 age and sex-matched HIV-negative Ugandans; all were >45 years old with >1 cardiovascular disease risk factor. Subjects underwent ECG-gated non-contrast cardiac CT and transthoracic echocardiography with speckle tracking strain imaging. Multivariable linear and logistic regression models were used to explore the association of PCF with echocardiographic outcomes.ResultsMedian age was 55% and 62% were female. Compared with uninfected controls, PLHIV had lower body mass index (27 vs 30, p=0.02) and less diabetes (26% vs 45%, p=0.005). Median left ventricular (LV) ejection fraction was 67%. In models adjusted for traditional risk factors, HIV was associated with 10.3 g/m2 higher LV mass index (LVMI) (95% CI 3.22 to 17.4; p=0.005), 0.87% worse LV global longitudinal strain (GLS) (95% CI −1.66 to −0.07; p=0.03) and higher odds of diastolic dysfunction (OR 1.96; 95% CI 0.95 to 4.06; p=0.07). In adjusted models, PCF volume was significantly associated with increased LVMI and worse LV GLS, while PCF radiodensity was associated with worse LV GLS (all pConclusionsIn Uganda, HIV infection, PCF volume and density are associated with abnormal cardiac structure and function.

Persons living with human immunodeficiency virus (PLHIV) are at increased risk of atherosclerotic cardiovascular disease (ASCVD). In spite of this, uptake of evidence-based clinical interventions for ASCVD risk reduction in the HIV clinic setting is sub-optimal. METHODS: EXTRA-CVD is a 12-month randomized clinical effectiveness trial that will assess the efficacy of a multi-component nurse-led intervention in reducing ASCVD risk among PLHIV. Three hundred high ASCVD risk PLHIV across three sites will be randomized 1:1 to usual care with generic prevention education or the study intervention. The study intervention will consist of four evidence-based components: (1) nurse-led care coordination, (2) nurse-managed medication protocols and adherence support (3) home BP monitoring, and (4) electronic health records support tools. The primary outcome will be change in systolic blood pressure and secondary outcome will be change in non-HDL cholesterol over the course of the intervention. Tertiary outcomes will include change in the proportion of participants in the following extended cascade categories: (1) appropriately diagnosed with hypertension and hyperlipidemia (2) appropriately managed; (3) at treatment goal (systolic blood pressure130 mm Hg and non-HDL cholesterolNational Lipid Association targets). CONCLUSIONS: The EXTRA-CVD trial will provide evidence appraising the potential impact of nurse-led interventions in reducing ASCVD risk among PLHIV, an essential extension of the HIV care continuum beyond HIV viral suppression.

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

Our objective was to examine the effect of a lifestyle diet and exercise intervention on cardiorespiratory fitness (CRF) and to examine predictors of change in CRF.People living with HIV (PLHIV) are at increased risk for cardiovascular disease. CRF is a better predictor of cardiovascular disease-related mortality than established risk factors yet very little is known about CRF in PLHIV.One-hundred and seven virally suppressed PLHIV were randomized to a group-based intervention to improve lifestyle behaviors or a control condition. All PLHIV maximal cardiorespiratory stress test to determine VO2 peak, VO2 at anaerobic threshold, and ventilatory efficiency/VCO2, at baseline and 6 months later. Participants wore an accelerometer to measure physical activity, completed waist-hip circumference measures, and had a fasting lipid profile, IL-6, and high sensitivity C-reactive protein analyzed. Generalized estimating equations were used to examine the effect of the intervention on CRF and predictors of change in CRF.Participants were approximately 53 years old, 65% male (n = 70), and 86% African-American (n = 93). There was no effect of the intervention on markers of CRF over time (P 0.05). After controlling for age, sex, waist-hip-ratio, the inflammatory biomarker IL-6 was inversely associated with a decline in both VO2 peak (P = 0.03) and VO2 at anaerobic threshold (P = 0.03). In addition, participants who walked an additional 10 000 steps per day had a 2.69 ml/kg per min higher VO2 peak (P = 0.02).Despite HIV viral suppression, PLHIV had remarkably poor CRF and inflammation was associated with a clinically adverse CRF profile. However, increased physical activity was associated with improved CRF.

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.

Objectives To adapt a World Health Organization HEARTS-based implementation strategy for hypertension (HTN) control at a large urban HIV clinic in Uganda and determine six-month HTN and HIV outcomes among a cohort of adult persons living with HIV (PLHIV). Methods Our implementation strategy included six elements: health education, medication adherence, and lifestyle counseling; routine HTN screening; task shifting of HTN treatment; evidence-based HTN treatment protocol; consistent supply of HTN medicines free to patients; and inclusion of HTN-specific monitoring and evaluation tools. We conducted a pre-post study from October 2019 to March 2020 to determine the effect of this strategy on HTN and HIV outcomes at baseline and six months. Our cohort comprised adult PLHIV diagnosed with HTN who made at least one clinic visit within two months prior to study onset. Findings We enrolled 1,015 hypertensive PLHIV. The mean age was 50.1 ± 9.5 years and 62.6% were female. HTN outcomes improved between baseline and six months: mean systolic BP (154.3 ± 20.0 to 132.3 ± 13.8 mmHg, p p p 95% at baseline and six months) and viral suppression was unchanged (98.7% to 99.2%, p = 0.712). Taking ART for more than two years and HIV viral suppression were independent predictors of HTN control at six months. Conclusions A HEARTS-based implementation strategy at a large, urban HIV center facilitates integration of HTN and HIV care and improves HTN outcomes while sustaining HIV control. Further implementation research is needed to study HTN/HIV integration in varied clinical settings among diverse populations.

Introduction To address workforce shortages and expand access to care, we developed a telemedicine program incorporating existing infrastructure for delivery of cardiovascular care in Gulu, Northern Uganda. Our study had three objectives: 1) assess feasibility and clinical impact 2) evaluate patient/parent satisfaction and 3) estimate costs. Methods All cardiology clinic visits during a two-year study period were included. All patients received an electrocardiogram and echocardiogram performed by a local nurse in Gulu which were stored and transmitted to the Uganda Heart Institute in the capital of Kampala for remote consultation by a cardiologist. Results were relayed to patients/families following cardiologist interpretation. The following telemedicine process was utilized: 1) clinical intake by nurse in Gulu; 2) ECG and echocardiography acquisition in Gulu; 3) echocardiography transmission to the Uganda Heart Institute in Kampala, Uganda; 4) remote telemedicine consultation by cardiologists in Kampala; and 5) communication of results to patients/families in Gulu. Clinical care and technical aspects were tracked. Diagnoses and recommendations were analyzed by age groups (0–5 years, 6–21 years, 22–50 years and > 50 years). A mixed methods approach involving interviews and surveys was used to assess patient satisfaction. Healthcare sector costs of telemedicine-based cardiovascular care were estimated using time-driven activity-based costing. Results Normal studies made up 47%, 55%, 76% and 45% of 1,324 patients in the four age groups from youngest to oldest. Valvular heart disease (predominantly rheumatic heart disease) was the most common diagnosis in the older three age groups. Medications were prescribed to 31%, 31%, 24%, and 48% of patients in the four age groups. The median time for consultation was 7 days. A thematic analysis of focus group transcripts displayed an overall acceptance and appreciation for telemedicine, citing cost- and time-saving benefits. The cost of telemedicine was $29.48/visit. Conclusions Our data show that transmission and interpretation of echocardiograms from a remote clinic in northern Uganda is feasible, serves a population with a high burden of heart disease, has a significant impact on patient care, is favorably received by patients, and can be delivered at low cost. Further study is needed to better assess the impact relative to existing standards of care and cost effectiveness.

Background Acute rheumatic fever is infrequently diagnosed in sub-Saharan African countries despite the high prevalence of rheumatic heart disease. We aimed to determine the incidence of acute rheumatic fever in northern and western Uganda. Methods For our prospective epidemiological study, we established acute rheumatic fever clinics at two regional hospitals in the north (Lira district) and west (Mbarara district) of Uganda and instituted a comprehensive acute rheumatic fever health messaging campaign. Communities and health-care workers were encouraged to refer children aged 3-17 years, with suspected acute rheumatic fever, for a definitive diagnosis using the Jones Criteria. Children were referred if they presented with any of the following: (1) history of fever within the past 48 h in combination with any joint complaint, (2) suspicion of acute rheumatic carditis, or (3) suspicion of chorea. We excluded children with a confirmed alternative diagnosis. We estimated incidence rates among children aged 5-14 years and characterised clinical features of definite and possible acute rheumatic fever cases. Findings Data were collected between Jan 17, 2018, and Dec 30, 2018, in Lira district and between June 5, 2019, and Feb 28, 2020, in Mbarara district. Of 1075 children referred for evaluation, 410 (38%) met the inclusion criteria; of these, 90 (22%) had definite acute rheumatic fever, 82 (20·0%) had possible acute rheumatic fever, and 24 (6%) had rheumatic heart disease without evidence of acute rheumatic fever. Additionally, 108 (26%) children had confirmed alternative diagnoses and 106 (26%) had an unknown alternative diagnosis. We estimated the incidence of definite acute rheumatic fever among children aged 5-14 years as 25 cases (95% CI 13·7-30·3) per 100 000 person-years in Lira district (north) and 13 cases (7·1-21·0) per 100 000 person-years in Mbarara district (west). Interpretation To the best of our knowledge, this is the first population-based study to estimate the incidence of acute rheumatic fever in sub-Saharan Africa. Given the known rheumatic heart disease burden, it is likely that only a proportion of children with acute rheumatic fever were diagnosed. These data dispel the long-held hypothesis that the condition does not exist in sub-Saharan Africa and compel investment in improving prevention, recognition, and diagnosis of acute rheumatic fever. Funding American Heart Association Children's Strategically Focused Research Network Grant, THRiVE-2, General Electric, and Cincinnati Children's Heart Institute Research Core.

Background Although ≈70% of the world's population of people living with HIV reside in sub‐Saharan Africa, there are minimal prospective data on the contributions of HIV infection to atherosclerosis in the region. Methods and Results We conducted a prospective observational cohort study of people living with HIV on antiretroviral therapy >40 years of age in rural Uganda, along with population‐based comparators not infected with HIV. We collected data on cardiovascular disease risk factors and carotid ultrasound measurements annually. We fitted linear mixed effects models, adjusted for cardiovascular disease risk factors, to estimate the association between HIV serostatus and progression of carotid intima media thickness (cIMT). We enrolled 155 people living with HIV and 154 individuals not infected with HIV and collected cIMT images at 1045 visits during a median of 4 annual visits per participant (interquartile range 3–4, range 1–5). Age (median 50.9 years) and sex (49% female) were similar by HIV serostatus. At enrollment, there was no difference in mean cIMT by HIV serostatus (0.665 versus 0.680 mm, P =0.15). In multivariable models, increasing age, blood pressure, and non–high‐density lipoprotein cholesterol were associated with greater cIMT ( P P =0.25). Conclusions In rural Uganda, treated HIV infection was not associated with faster cIMT progression. These results do not support classification of treated HIV infection as a risk factor for subclinical atherosclerosis progression in rural sub‐Saharan Africa. Registration URL: https://www.ClinicalTrials.gov ; Unique identifier: NCT02445079.

The recently revised 2017 American College of Cardiology/American Heart Association (ACC/AHA) hypertension (HTN) guidelines employ a lower blood pressure threshold to define HTN, aiming for earlier prevention of HTN-related cardiovascular diseases (CVD). Thoracic aortic calcification (TAC), a new surrogate marker of aging and aortic medial layer degeneration, and different stages of HTN, according to the 2017 ACC/AHA HTN guidelines, remain unknown. We classified 3022 consecutive asymptomatic individuals enrolled into four HTN categories using the revised 2017 ACC/AHA guidelines: normal blood pressure (NBP), elevated blood pressure (EBP), and stage 1 (S1) and stage 2 (S2) HTN. The coronary artery calcification score and TAC metrics (total Agaston TAC score, total plaque volume (mm3), and mean density (Hounsfield units, HU)) were measured using multi-detector computed tomography. Compared to NBP, a graded and significant increase in the TAC metrics was observed starting from EBP and S1 and S2 HTN, using the new 2017 ACC/AHA guidelines (NBP as reference, all trends: p &lt, 0.001). These differences remained consistent after being fully adjusted. Older age (&gt, 50 years), S1 and S2 HTN, prevalent diabetes, and chronic kidney disease (&lt, 60 mL/min/1.73 m2) are all independently contributing factors to higher TAC risk using multivariate stepwise logistic regressions (all p ≤ 0.001). The optimal cutoff values of systolic blood pressure, diastolic blood pressure, and pulse pressure were 121, 74, and 45 mmHg, respectively, for the presence of TAC after excluding subjects with known CVD and ongoing HTN medication treatment. Our data showed that the presence of TAC starts at a stage of elevated blood pressure not categorized as HTN from the updated 2017 ACC/AHA hypertension guidelines.

Background Biomarkers of myocardial stress and fibrosis are elevated in people living with HIV and are associated with cardiac dysfunction. It is unknown whether sex influences these markers of heart failure risk in sub‐Saharan Africa, where HIV burden is high and where the vast majority of women with HIV live. Methods and Results Echocardiograms and 6 plasma biomarkers (suppression of tumorigenicity‐2, growth differentiation factor 15, galectin 3, soluble fms‐like tyrosine kinase‐1, NT‐proBNP [N‐terminal pro‐B‐type natriuretic peptide], and cystatin C) were obtained from 100 people living with HIV on antiretroviral therapy and 100 HIV‐negative controls in Uganda. All participants were ≥45 years old with ≥1 major cardiovascular risk factor. Multivariable linear and logistic regression models were used to assess associations between biomarkers, echocardiographic variables, HIV status, and sex, and to assess whether sex modified these associations. Overall, mean age was 56 years and 62% were women. Suppression of tumorigenicity‐2 was higher in men versus women ( P P P for interaction P= 0.02), but there was no evidence of sex‐modifying HIV effects on cardiac structure and function. Cardiac biomarkers were more strongly associated with left ventricular mass index in men compared with women. Conclusions There are prominent differences in biomarkers of cardiac fibrosis and stress by sex and HIV status in Uganda. The predictive value of cardiac biomarkers for heart failure in people living with HIV in sub‐Saharan Africa should be examined, and novel risk markers for women should be further explored.

Background: Low- and-middle-income-countries (LMICs) currently bear 80% of the world’s cardiovascular disease (CVD) mortality burden. The same countries are underequipped to handle the disease burden due to critical shortage of resources. Functional cardiac catheterization laboratories (cath labs) are central in the diagnosis and management of CVDs. Yet, most LMICs, including Uganda, fall remarkably below the minimum recommended standards of cath lab:population ratio due to a host of factors including the start-up and recurring costs. Objectives: To review the performance, challenges and solutions employed, lessons learned, and projections for the future for a single cath lab that has been serving the Ugandan population of 40 million people in the past eight years. Methods: A retrospective review of the Uganda Heart Institute cath lab clinical database from 15 February 2012 to 31 December 2019 was performed. Results: In the initial two years, this cath lab was dependent on skills transfer camps by visiting expert teams, but currently, Ugandan resident specialists independently operate this lab. 3,542 adult and pediatric procedures were conducted in 8 years, including coronary angiograms and percutaneous coronary interventions, device implantations, valvuloplasties, and cardiac defect closures, among others. There was a consistent expansion of the spectrum of procedures conducted in this cath lab each year. The initial lack of technical expertise and sourcing for equipment, as well as the continual need for sundries present(ed) major roadblocks. Government support and leveraging existing multi-level collaborations has provided a platform for several solutions. Sustainability of cath lab services remains a significant challenge especially in relation to the high cost of sundries and other consumables amidst a limited budget. Conclusion: A practical example of how centers in LMIC can set up and sustain a public cardiac catheterization laboratory is presented. Government support, research, and training collaborations, if present, become invaluable leverage opportunities.

Background Tuberculosis (TB) has been linked to an increased risk of atherosclerotic cardiovascular disease (ASCVD). We assessed whether latent TB infection (LTBI) is associated with subclinical coronary atherosclerosis in 2 TB-prevalent areas. Methods We analyzed cross-sectional data from studies conducted in Lima, Peru, and Kampala, Uganda. Individuals ≥40 years old were included. We excluded persons with known history of ASCVD events or active TB. Participants underwent QuantiFERON-TB (QFT) testing to define LTBI and computed tomography angiography to examine coronary atherosclerosis. A Coronary Artery Disease–Reporting Data System (CAD-RADS) score ≥3 defined obstructive CAD (plaque causing ≥50% stenosis). Results 113 and 91 persons with and without LTBI, respectively, were included. There were no significant differences between LTBI and non-LTBI participants in terms of age (median [interquartile range]; 56 [51–62] vs 55 [49–64] years; P = .829), male sex (38% vs 42%; P = .519), or 10-year ASCVD risk scores (7.1 [3.2–11.7] vs 6.1 [2.8–1.8]; P = .533). CAD prevalence (any plaque) was similar between groups (29% vs 24%; P = .421). Obstructive CAD was present in 9% of LTBI and 3% of non-LTBI individuals (P = .095). LTBI was associated with obstructive CAD after adjusting for ASCVD risk score, HIV status, and study site (adjusted OR, 4.96; 95% CI, 1.05–23.44; P = .043). Quantitative QFT TB antigen minus Nil interferon-γ responses were associated with obstructive CAD (adjusted OR, 1.2; 95% CI, 1.03–1.41; P = .022). Conclusions LTBI was independently associated with an increased likelihood of subclinical obstructive CAD. Our data indicate that LTBI is a nontraditional correlate of ASCVD risk.