The temporal relationship between body composition and cardiometabolic profiles in an HIV-infected (on antiretroviral therapy) versus HIV-free Western Cape study population.

Cardiovascular risk is a health concern in people living with HIV/AIDS (PLWH). This longitudinal study (baseline vs 36 months) aimed to investigate the relationship between body composition and markers of cardiovascular risk in a South African study population [HIV free, n = 22 vs HIV positive on antiretroviral therapy (HIV+ART), n = 73)]. Health questionnaires, anthropometric measurements, biochemical analyses and flow-mediated dilation were performed. Linear mixed-model statistical analyses were applied. The HIV+ART vs the HIV-free groups were independently associated with body mass index (BMI) [-4.92 (-7.99 to -1.84), p = 0.002] and waist circumference [-10.5 (-17.2 to -3.77), p = 0.003]. ART duration was associated with BMI [2.60 (0.57-4.62), p = 0.013], waist circumference [3.83 (0.03-7.63), p = 0.048] and high-density lipoprotein cholesterol [20.18 (2.37-41.09), p = 0.025]. The data showed that intricate relationships existed in this study population between HIV, ART, body composition and cardiometabolic variables. There is a need for more research investigating cardiovascular risk in PLWH, particularly in the context of changes in body composition measures.

HIV and Antiretroviral Therapy Are Independently Associated with Cardiometabolic Variables and Cardiac Electrical Activity in Adults from the Western Cape Region of South Africa.

Cardiovascular-related complications are on the rise in people with HIV/AIDS (PWH); however, the relationship among HIV and antiretroviral therapy (ART)-related parameters, cardiovascular risk, and cardiac electrical activity in PWH remain poorly studied, especially in sub-Saharan African populations. We investigated whether HIV and ART are associated with cardiometabolic and cardiac electrical activity in PWH from Worcester in the Western Cape Province, South Africa. This was a cross-sectional study with HIV-negative (HIV-, n = 24) and HIV-positive on ART (HIV+/ART+, n = 63) participants. We obtained demographic, lifestyle, and medical history data and performed anthropometric, clinical assessments, and blood/urine biochemistry. We performed multiple stepwise linear regression analyses to determine independent associations among HIV, ART, cardiometabolic, and electrocardiographic (ECG) variables. HIV+/ART+ independently associated with a lower body mass index (p = 0.004), elevated gamma-glutamyl transferase levels (ß: 0.333 (0.130-0.573); p = 0.002), and elevated alanine aminotransferase levels (ß: 0.427 (0.224-0.629); p < 0.001) compared to HIV-. Use of second-line ART was positively associated with high-sensitivity C-reactive protein (p = 0.002). Although ECG parameters did not differ between HIV- and HIV+/ART+, viral load positively associated with p-wave duration (0.306 (0.018-0.594); p = 0.038), and longer HIV duration (≥5 years) with ST-interval (0.270 (0.003-0.537); p = 0.047) after adjusting for confounding factors. Our findings suggest that HIV and ART are associated with mixed effects on this population's cardiometabolic profile and cardiac electrical activity, underpinning the importance of cardiovascular risk monitoring in PWH.

Mobility Deviations in Adults With Human Immunodeficiency Virus: A Cross-Sectional Assessment Using Gait Analysis, Functional Performance, and Self-Report.

BACKGROUND: Little is known about how human immunodeficiency virus (HIV) affects walking biomechanics, or about associations between HIV-related gait deviations, functional performance, and self-reported outcomes. This paper reports on (1) gait biomechanics and variability in people with HIV (PWH) and (2) associations with clinical tests, self-reported function, and falls. METHODS: A cross-sectional study tested consecutively sampled PWH (n = 50) and HIV-seronegative participants ([SNP] n = 50). Participants underwent 3-dimensional gait analysis, performed clinical tests (short walk and single leg stance tests with and without dual tasking, chair-rise tests, and a physical performance battery), and completed questionnaires about function and falls. Between-group comparisons were done using analysis of covariance. Linear correlations between gait variability, clinical tests, and patient-reported outcomes were established. RESULTS: People with HIV and SNP had comparable median ages (PWH = 36.6, interquartile range [IQR] = 32.0-45.6]; SNP = 31.1, IQR = 23.2-45.1). Compared with SNP, PWH walked slower (adjusted mean difference [MD] = -0.2 meters per second [m/s], 95% confidence interval [CI] = -0.3 to -0.1) with greater variability (adjusted MD = 14.7 variability score points, 95% CI = 9.9-19.5). Moreover, PWH were slower in five-times sit-to-stand (5STS) performance (adjusted MD = 1.9 seconds, 95% CI = 1.00-2.9). Significant deviations in hip kinematics (increased flexion; adjusted MDs = 2.4°-2.8°, P = .012-.016) and knee kinematics (reduced flexion; adjusted MDs = 2.3°-3.7°, P = .007-.027) were found in PWH during dual-task (DT) walking. The PWH's 5STS moderately correlated with larger gait variability (usual pace r = -0.5; dual task r = -0.6), poorer self-reported mobility (r = 0.4) and self-care function (r = 0.5), and fear of falling (P = .003). CONCLUSIONS: People with HIV presented with biomechanical deviations suggestive of a slowed and variable gait, especially under cognitive challenges. Five-times STS may be useful to screen for gait deviations in PWH.

Relationship between Endothelial Function, Antiretroviral Treatment and Cardiovascular Risk Factors in HIV Patients of African Descent in South Africa: A Cross-Sectional Study.

Limited information on the effect of antiretroviral treatment (ART) on vascular function in South Africans of African descent living with human immunodeficiency virus (HIV) is available. The relationship between ART, vascular function and cardiovascular risk factors in South Africans of African ancestry with HIV was therefore studied. This cross-sectional study recruited 146 HIV-positive individuals on ART (HIV+ART+), 163 HIV-positive individuals not on ART (HIV+ART-) and 171 individuals without HIV (HIV-) in Mthatha, Eastern Cape Province of South Africa. Flow-mediated dilation (FMD) test was performed to assess endothelial function. Anthropometry and blood pressure parameters were measured. Lipid profile, glycaemic indices, serum creatinine as well as CD4 count and viral load were assayed in blood. Urinary albumin to creatinine ratio (ACR) was determined as a marker of cardiovascular risk. Obesity and albuminuria were positively associated with HIV, and HIV+ART+ participants had significantly higher HDL cholesterol. Dyslipidaemia markers were significantly higher in hypertensive HIV+ART+ participants compared with the controls (HIV+ART- and HIV- participants). FMD was not different between HIV+ART+ participants and the controls. Moreover, HIV+ART+ participants with higher FMD showed lower total cholesterol and LDL cholesterol comparable to that of HIV- and HIV+ART- participants. A positive relationship between FMD and CD4 count was observed in HIV+ART+ participants. In conclusion, antiretroviral treatment was associated with cardiovascular risk factors, particularly dyslipidaemia, in hypertensive South Africans of African ancestry with HIV. Although, ART was not associated with endothelial dysfunction, flow-mediated dilatation was positively associated with CD4 count in HIV-positive participants on ART.

Vascular health assessment with flow-mediated dilatation and retinal image analysis: a pilot study in an adult population from Cape Town.

AIM: Flow-mediated dilatation (FMD) and retinal vascular analysis (RVA) may assist in predicting cardiovascular disease (CVD) but are poorly characterised in South Africa. We recorded baseline FMD and retinal vascular widths in healthy participants, and investigated associations with cardiovascular risk factors. METHODS: Endothelial function (measured with FMD), microvascular structure (evaluated via fundus image analysis) and major CVD risk factors were assessed in 66 participants from Cape Town. RESULTS: Median FMD% was 9.6%, with higher values in females. Mean retinal arteriolar and venular widths were ˜156 and ˜250 µm, respectively. FMD was not associated with CVD risk factors. Hypertension was associated with narrower retinal arterioles and venules. CONCLUSIONS: We report novel baseline FMD data in healthy South African adults from the Western Cape, and show that retinal microvascular calibres are associated with blood pressure. Our baseline FMD and RVA data could serve as a reference for future studies in South Africa.

Personal exposure to NO2 and benzene in the Cape Town region of South Africa is associated with shorter leukocyte telomere length in women.

Air pollution exposure is a major global health concern and has been associated with molecular aging. Unfortunately, the situation has not received much attention in the African region. The aim of this study was to investigate whether current personal ambient NO2 and benzene, toluene, ethyl-benzene and xylenes (ortho (o)-, meta (m)- and para (p)-xylene (BTEX) exposure is associated with leukocyte telomere length (LTL), a marker of molecular ageing, in apparently healthy women (mean ± SD age: 42.5 ± 13.4 years) residing in the Cape Town region of South Africa. The repeated measures study collected data from 61 women. Seven-day median (interquartile range (IQR)) personal NO2 and BTEX exposure levels were determined via compact passive diffusion samplers carried on the person prior to baseline (NO2: 14.2 (9.4-17.2) µg/m³; Benzene: 3.1 (2.1-5.3) µg/m³) and 6-month follow-up (NO2: 10.6 (6.6-13.6) µg/m³; Benzene: 2.2 (1.3-4.9) µg/m³) visits. LTL was measured at baseline and follow-up using a real-time PCR method. Multiple linear mixed model analyses (adjusting for age, body mass index, smoking, employment status, level of education and assessment visit) showed that each IQR increment increase in NO2 (7.0 µg/m³) and benzene (3.3 µg/m³) was associated with -7.30% (95% CI: -10.98 to -3.46%; p < 0.001) and -6.78% (95% CI: -11.88 to -1.39%; p = 0.015) difference in LTL, respectively. The magnitude of these effects of NO2 and benzene corresponds to the effect of an increase of 10.3- and 6.0-year in chronological age on LTL. Our study shows that personal exposures to NO2 and benzene are associated with molecular ageing as indicated by LTL in healthy women residing in the Cape Town region.

Fall History and Associated Factors Among Adults Living With HIV-1 in the Cape Winelands, South Africa: An Exploratory Investigation.

BACKGROUND: People with HIV-1 (PWH) exhibit a high fall incidence and increased fracture risk. As little is known about fall frequency and associated factors in PWH residing in lower-middle-income countries (LMIC), we investigated fall frequency, bone quality, and factors associated with fall history in a South African cohort. METHODS: Fifty PWH without obvious predisposing factors for mobility impairments attending 2 public primary care clinics in the Western Cape region participated. Demographic, clinical, and physical performance data were collected. Falls were assessed retrospectively over 12 months. Mobility and balance were evaluated using a physical performance battery. Bone mineral density was screened using quantitative ultrasound (QUS). Associations between variables and falls grouping were analyzed using chi-square tests, t tests, and Mann-Whitney U tests, and effect sizes (ES) were calculated. RESULTS: Thirty-four percent of PWH (median age, 36.6 years) reported falling during the past year, and 41.2% of fallers reported multiple falls. Fallers had more mobility problems (P = .013), higher fear of falling (P = .007), higher fracture history (P = .003), worse balance performance (P < .001), higher proportions of detectable viral loads (P = .021), and poorer bone quality (P = .040). Differences were of medium to large ES. CONCLUSIONS: This exploratory study is the first to show that relatively young South African PWH without obvious predisposing factors for gait and balance impairments experience falls. The observed fall-associated factors warrant further research using larger samples and longitudinal designs to ascertain fall predictors within this population.

Personal NO2 and Volatile Organic Compounds Exposure Levels are Associated with Markers of Cardiovascular Risk in Women in the Cape Town Region of South Africa.

Exposure to ambient NO2 and benzene, toluene ethyl-benzene and m+p- and o-xylenes (BTEX) is associated with adverse cardiovascular effects, but limited information is available on the effects of personal exposure to these compounds in South African populations. This 6-month follow-up study aims to determine 7-day personal ambient NO2 and BTEX exposure levels via compact passive diffusion samplers in female participants from Cape Town, and investigate whether exposure levels are associated with cardiovascular risk markers. Overall, the measured air pollutant exposure levels were lower compared to international standards. NO2 was positively associated with systolic and diastolic blood pressure (SBP and DBP), and inversely associated with the central retinal venular equivalent (CRVE) and mean baseline brachial artery diameter. o-xylene was associated with DBP and benzene was strongly associated with carotid intima media thickness (cIMT). Our findings showed that personal air pollution exposure, even at relatively low levels, was associated with several markers of cardiovascular risk in women residing in the Cape Town region.

Histomorphological changes in the pancreas and kidney and histopathological changes in the liver in male Wistar rats on antiretroviral therapy and melatonin treatment.

Combination antiretroviral therapy (cART) has shown to cause inflammation, cellular injury and oxidative stress, whereas melatonin has been successful in reducing these effects. The aim of the study was to determine potential morphometric changes caused by cART in combination with melatonin supplementation in human immunodeficiency virus (HIV)-free rats. Tissue samples (N = 40) of the pancreas, liver and kidney from a control (C/ART-/M-), cART group (C/ART + ), melatonin (C/M + ) and experimental group (ART+/M + ) were collected and stained with haematoxylin and eosin (H&E) and evaluated for histopathology. The pancreata were labelled with anti-insulin and anti-glucagon to determine α- and ß-cell regions. Kidneys were stained with periodic acid Schiff (PAS) to measure the area, perimeter, diameter and radius of renal corpuscles, glomeruli and proximal convoluted tubules (PCTs). Blood tests were conducted to determine hepatotoxicity. No significant changes in histopathology were seen. Melatonin stimulated pancreatic islet abundance, as the number of islets per mm2 was significantly higher in the C/M+ than in the C/ART-/M- and ART+/M+. Parameters of the renal corpuscle, glomeruli, renal space and PCTs were significantly lower in the C/ART+ compared to the other groups, thus cART may have caused tubular dysfunction or cellular damage. A significant increase in serum haemoglobin was observed in the C/ART+ compared to the C/ART-, which showed cART increases serum haemoglobin in the absence of immune deficiency. Serum lipids were significantly decreased in the C/M+ compared to the C/ART-, possibly due to the effect of melatonin on the decrease of lipolysis, decreasing effect on cholesterol absorption and stimulation of lipoprotein lipase (LPL) activity. In conclusion, we have demonstrated that melatonin stimulated α-cell production, increased the number of pancreatic islets and caused a decrease in total lipids, whereas cART increased serum haemoglobin and decreased various parameters of the nephron in an HIV-free rat model, suggestive of tubular dysfunction.

The Role of MKP-1 in Insulin-Induced Cardioprotection.

PURPOSE: The mitogen-activated protein kinase phosphatases (MKPs) are a family of dual-specificity phosphatases that inactivate MAPKs by dephosphorylation. Impairment of MKP-1 expression in insulin resistance has been suggested to affect the cardioprotective properties of insulin. We hypothesized that manipulation of its activity during myocardial ischaemia/reperfusion of control as well as insulin-resistant rats may affect the outcome. METHODS: Hearts from 16 week dietary induced obese Wistar rats and their age matched controls were isolated, perfused in the working mode and subjected to 15 min global ischaemia / 30 min reperfusion or 35 min coronary artery ligation/ 60 min reperfusion. Hearts received insulin (1mIU/ml), a MKP-1 inhibitor (sanguinarine 2.5uM), or insulin + sanguinarine for 15 min pre- and 10 min post-ischaemia. Endpoints were functional recovery and infarct size. Hearts from control and experimental groups were freeze-clamped either immediately after removal from the animal (baseline) or at 10 min reperfusion after global ischaemia and Western blot analysis done for total and phosphorylated MKP-1. RESULTS: Insulin treatment significantly increased total work recovery while sanguinarine abolished the insulin-mediated protection. Insulin had no effect on infarct size while sanguinarine reduced infarct size. Insulin increased while sanguinarine attenuated phosphorylation of MKP-1 at 10 min reperfusion. CONCLUSION: Inhibition of MKP-1 with sanguinarine abolished the insulin-induced improvement in functional recovery, but reduced infarct size. Although the data suggest a role for this phosphatase in insulin-induced cardioprotection, the multiple downstream effects of insulin hamper interpretation of the data obtained. In addition, the effects of sanguinarine per se in myocardial ischaemia/reperfusion need to be further elucidated.

Cardiovascular risk and endothelial function in people living with HIV/AIDS: design of the multi-site, longitudinal EndoAfrica study in the Western Cape Province of South Africa.

BACKGROUND: There is growing evidence of an interaction between HIV-infection, anti-retroviral therapy (ART) and cardiovascular diseases (CVD). Epidemiological studies in Europe and North America have been observing a shift towards an increased incidence of coronary heart disease and acute myocardial infarctions in HIV-infected populations compared to the general population even after adjusting for traditional cardiovascular risk factors. Despite South Africa (and sub-Saharan Africa, SSA) being regarded as the epicentre of the global HIV epidemic, very little is known about the prevalence of cardiovascular risk factors and precursors of vascular disease in HIV-infected populations in this region. The knowledge gap is further widened by the paucity of data from prospective studies. We present the rationale, objectives and key methodological features of the EndoAfrica study, which aims to determine whether HIV-infection and ART are associated with altered cardiovascular risk and changes in vascular endothelial structure and function in adults living in the Western Cape Province of South Africa. METHODS: In this longitudinal study, comprehensive cardiovascular assessments of HIV-negative and HIV-positive (with and without ART) study participants are performed by clinical and biochemical screening for traditional cardiovascular risk factors and biomarkers of CVD. Vascular and endothelial function is determined by brachial artery flow-mediated dilatation (FMD), carotid-intima-thickness (IMT) measurements and quantitative retinal blood vessel analyses, complemented by vascular endothelial biomarker assays. Finally, we aim to statistically determine whether HIV-infection and/or ART are associated with increased cardiovascular risk and vascular endothelial dysfunction, and determine whether there is progression/regression in these endpoints 18 months after the baseline assessments. DISCUSSION: The EndoAfrica study provides a unique opportunity to recruit a cohort of HIV-infected patients and HIV-negative controls who will be comprehensively and longitudinally assessed for cardiovascular risk and disease profile with vascular endothelial function as a potentially important intermediate cardiovascular phenotype. To our knowledge, it is the first time that such a systematic study has been established in the context of SSA and South Africa.