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.

Immunologic and vascular biomarkers of mortality in critical COVID-19 in a South African cohort.

Introduction: Biomarkers predicting mortality among critical Coronavirus disease 2019 (COVID-19) patients provide insight into the underlying pathophysiology of fatal disease and assist with triaging of cases in overburdened settings. However, data describing these biomarkers in Sub-Saharan African populations are sparse. Methods: We collected serum samples and corresponding clinical data from 87 patients with critical COVID-19 on day 1 of admission to the intensive care unit (ICU) of a tertiary hospital in Cape Town, South Africa, during the second wave of the COVID-19 pandemic. A second sample from the same patients was collected on day 7 of ICU admission. Patients were followed up until in-hospital death or hospital discharge. A custom-designed 52 biomarker panel was performed on the Luminex® platform. Data were analyzed for any association between biomarkers and mortality based on pre-determined functional groups, and individual analytes. Results: Of 87 patients, 55 (63.2%) died and 32 (36.8%) survived. We found a dysregulated cytokine response in patients who died, with elevated levels of type-1 and type-2 cytokines, chemokines, and acute phase reactants, as well as reduced levels of regulatory T cell cytokines. Interleukin (IL)-15 and IL-18 were elevated in those who died, and levels reduced over time in those who survived. Procalcitonin (PCT), C-reactive protein, Endothelin-1 and vascular cell adhesion molecule-1 were elevated in those who died. Discussion: These results show the pattern of dysregulation in critical COVID-19 in a Sub-Saharan African cohort. They suggest that fatal COVID-19 involved excessive activation of cytotoxic cells and the NLRP3 (nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3) inflammasome. Furthermore, superinfection and endothelial dysfunction with thrombosis might have contributed to mortality. HIV infection did not affect the outcome. A clinically relevant biosignature including PCT, pH and lymphocyte percentage on differential count, had an 84.8% sensitivity for mortality, and outperformed the Luminex-derived biosignature.

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.

Cardiovascular effects of air pollution: current evidence from animal and human studies.

Air pollution is a global health concern. Particulate matter (PM)2.5, a component of ambient air pollution, has been identified by the World Health Organization as one of the pollutants that poses the greatest threat to public health. Cardiovascular health effects have been extensively documented, and these effects are still being researched to provide an overview of recent literature regarding air pollution-associated cardiovascular morbidity and mortality in humans. Additionally, potential mechanisms through which air pollutants affect the cardiovascular system are discussed based on human and additional animal studies. We used the strategy of a narrative review to summarize the scientific literature of studies that were published in the past 7 yr. Searches were carried out on PubMed and Web of Science using predefined search queries. We obtained an initial set of 800 publications that were filtered to 78 publications that were relevant to include in this review. Analysis of the literature showed significant associations between air pollution, especially PM2.5, and the risk of elevated blood pressure (BP), acute coronary syndrome, myocardial infarction (MI), cardiac arrhythmia, and heart failure (HF). Prominent mechanisms that underlie the adverse effects of air pollution include oxidative stress, systemic inflammation, endothelial dysfunction, autonomic imbalance, and thrombogenicity. The current review underscores the relevance of air pollution as a global health concern that affects cardiovascular health. More rigorous standards are needed to reduce the cardiovascular disease burden imposed by air pollution. Continued research on the health impact of air pollution is needed to provide further insight.

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.

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.

Treatment with a fixed dose combination antiretroviral therapy drug containing tenofovir, emtricitabine and efavirenz is associated with cardioprotection in high calorie diet-induced obese rats.

HIV-infection, certain antiretroviral drug classes, especially protease inhibitors (PI), and obesity are associated with increased ischaemic heart disease (IHD) risk. However, the effect of PI-free fixed dose combination (FDC) antiretroviral therapy (ART) on hearts exposed to ischaemia-reperfusion injury (I/R) is unknown, particularly in obesity. This is becoming relevant as World Health Organisation guidelines recommend a FDC ART containing (non-) nucleoside reverse transcriptase inhibitors (tenofovir (TDF), emtricitabine (FTC) and efavirenz (EFV)) as first-line HIV treatment. Additionally, obesity rates are rising in HIV-infected populations, not only in ART-experienced individuals, but also at the time of ART initiation, which may further increase the risk of IHD. Therefore, we investigated the effects of PI-free FDC ART in myocardial I/R-exposed hearts from obese rats. Obesity was induced in male wistar rats via a 16-week high calorie diet. At week 10, treatment with a FDC ART drug containing TDF/FTC/EFV was initiated. Biometric and metabolic parameters, as well as myocardial functional recovery and infract size (IS), and myocardial signalling proteins following I/R were assessed after 16 weeks. Obese rats presented with increased body and intraperitoneal fat mass, elevated triglyceride and TBARS levels, whilst the hearts responded to I/R with impaired functional performance and increased IS. The FDC ART treatment did not alter biometric and metabolic parameters in obese rats. In a novel finding, ART protected obese hearts against I/R as shown by improved functional performance and smaller IS vs. untreated obese hearts. Cardioprotection was underscored by increased myocardial phosphorylated endothelial nitric oxide synthase (eNOS) and reduced AMP-kinase levels. In conclusion, these results demonstrate for the first time, that 6-weeks treatment of obese rats with a FDC ART drug specifically containing TDF/FTC/EFV conferred cardioprotection against I/R. The FDC ART-induced cardioprotection was seemingly unrelated to metabolic changes, but rather due to direct cardiac mechanisms including the up-regulation of myocardial eNOS.

Highly Active Antiretroviral Therapy Alters Sperm Parameters and Testicular Antioxidant Status in Diet-Induced Obese Rats.

The efficacy of highly active antiretroviral therapy (HAART) has led to an increase demand for therapeutic use, thereby necessitating investigation into drug toxicity. This study was designed to investigate the in vivo effects of HAART on sperm parameters and testicular oxidative stress in lean and obese rats. Wistar rats (males, n = 40, weighing 180~200 g) were assigned randomly into 4 groups and treated accordingly for 16 weeks as follows: Control (C): lean group fed with standard rat chow; Diet induced obesity (DIO): obese animals fed a high caloric diet; C + ART: lean animals treated with HAART; DIO + ART: obese animals treated with HAART. An antiretroviral drug combination of Tenofovir, Emtricitabine and Efavirenz at a dose of 17, 26 and 50 mg/kg/day was administered for the latter 6 weeks via jelly cube feeding. At the end of the experimental period, sperm analysis was performed on sperm collected from the caudal epididymis, while the testis was homogenized for antioxidant enzyme and lipid peroxidation assays. Results showed that HAART significantly decreased sperm motility (p < 0.05) in both lean and obese animals, and viability (p < 0.05) in the DIO group. Testicular glutathione, catalase and superoxide dismutase were significantly decreased (p < 0.05), while Thiobarbituric acid reactive substances (TBARS) levels were significantly increased (p < 0.05) when the DIO+ART group was compared to Control group. Thus, the decreased sperm qualities associated with HAART might be as a result of increased testicular oxidative stress prominent in obese animals.

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.

Mucin secreting cells in the stomach and colon are altered by combination antiretroviral treatment in an obese rat model.

Mucins, secreted by intestinal goblet cells, form an integral part of the intestinal biofilm, which is important for the functioning of a healthy gastrointestinal tract (GIT). This mucous layer is sensitive to factors such as diet, drugs and inflammation. Histochemically, mucins can be classified as neutral or acidic, where acidic mucins can contain sulphate groups (sulphomucins) or sialic acid (sialomucins). The aim of the present study was to determine the composition of various mucin secreting cells using histochemical stains in rats fed on a high calorie diet (HCD) treated with antiretroviral therapy (ART). Wistar rats (N=24) were divided into a lean control group (C/ART-), high calorie diet group (C/HCD+), ART group (C/ART+) and HCD and ART group (HCD+/ART+). The body of the stomach as well as the colon were stained with Alcian Blue Periodic Schiff (ABPAS) to distinguish between neutral and acidic mucins and Alcian Blue Aldehyde Fuschin (ABAF) to distinguish between sialo-and sulphomucins. An increase of the total gastric mucous cells was observed in the HCD+/ART+ group compared to the C/ART- group using both ABPAS and ABAF. A decrease of neutral cells in the distal part of the colonic crypts in the C/HCD+ and C/ART+ groups compared to the C/ART- group were observed. Mixed goblet cells in the colonic crypts of the C/ART- and HCD+/ART+ groups were decreased in comparison to the C/ART+ group. The study showed that the total mean percentage of mucous cells in the stomach as well as the total amount of neutral goblet cells in the colon were most affected by ART and a HCD. These changes in a rat model suggest that the quality of the biofilm may be altered and should be considered when ART is prescribed to obese patients.