People living with HIV display increased anti-apolipoprotein A1 auto-antibodies, inflammation, and kynurenine metabolites: a case-control study.

Objective: This study aimed to study the relationship between auto-antibodies against apolipoprotein A1 (anti-apoA1 IgG), human immunodeficiency virus (HIV) infection, anti-retroviral therapy (ART), and the tryptophan pathways in HIV-related cardiovascular disease. Design: This case-control study conducted in South Africa consisted of control volunteers (n = 50), people living with HIV (PLWH) on ART (n = 50), and untreated PLWH (n = 44). Cardiovascular risk scores were determined, vascular measures were performed, and an extensive biochemical characterisation (routine, metabolomic, and inflammatory systemic profiles) was performed. Methods: Anti-apoA1 IgG levels were assessed by an in-house ELISA. Inflammatory biomarkers were measured with the Meso Scale Discovery® platform, and kynurenine pathway metabolites were assessed using targeted metabolomic profiling conducted by liquid chromatography-multiple reaction monitoring/mass spectrometry (LC-MRM/MS). Results: Cardiovascular risk scores and vascular measures exhibited similarities across the three groups, while important differences were observed in systemic inflammatory and tryptophan pathways. Anti-apoA1 IgG seropositivity rates were 15%, 40%, and 70% in control volunteers, PLWH ART-treated, and PLWH ART-naïve, respectively. Circulating anti-apoA1 IgG levels were significantly negatively associated with CD4+ cell counts and positively associated with viremia and pro-inflammatory biomarkers (IFNγ, TNFα, MIPα, ICAM-1, VCAM-1). While circulating anti-apoA1 IgG levels were associated with increased levels of kynurenine in both control volunteers and PLWH, the kynurenine/tryptophan ratio was significantly increased in PLWH ART-treated. Conclusion: HIV infection increases the humoral response against apoA1, which is associated with established HIV severity criteria and kynurenine pathway activation.

Concentrations of Efavirenz, Tenofovir, and Emtricitabine in Obesity: A Cross-Sectional Study.

BACKGROUND: Obesity is increasing worldwide including in people living with HIV (PLWH). Antiretroviral pharmacokinetic data in obesity are limited. OBJECTIVES: To measure antiretroviral drug concentrations in obese and nonobese PLWH treated with the fixed-dose combination of efavirenz-tenofovir-emtricitabine. To determine pharmacokinetic differences across indicators of obesity and their associated immunovirological outcomes. METHODS: We conducted a cross-sectional sample analysis of 2 cohort studies. We measured mid-dose efavirenz, 8-hydroxy-efavirenz, tenofovir, and emtricitabine concentrations. Antiretroviral drug concentrations were analyzed by body mass index (BMI), waist circumference (WC), and waist-to-hip ratio (WHR). RESULTS: We performed a study of 213 participants: General obesity was detected in 20.4% using BMI and abdominal obesity in 53.6% using WC and 62.4% using WHR, respectively. The median concentrations of all antiretroviral drugs were lower among obese participants determined by BMI and WC, with efavirenz showing greater differences than tenofovir or emtricitabine. For BMI, results were most striking for efavirenz (1752.3 vs 2342.9 ng/mL, P = 0.002) with lower concentrations in obese participants. Using WC, efavirenz (1845.8 vs 2571.2 ng/mL, P < 0.001), tenofovir (65.8 vs 73.2 ng/mL, P = 0.036), and emtricitabine (159.5 vs 221.0 ng/mL, P = 0.005) concentrations were lower in obese participants. Eight-hydroxyefavirenz concentrations were similar in nonobese and obese participants for WC. Using WHR, the concentrations of all antiretroviral drugs were lower in the obese population, most strikingly for emtricitabine (173.5 vs 229.0 ng/mL, P = 0.015). There were no immunovirological associations. CONCLUSION: We found lower antiretroviral concentrations in all obese groups, most strikingly in participants with abdominal obesity determined by WC. Lower drug concentrations had no immunovirological associations.

Comparison of endothelial function and cardiometabolic profiles of people living with HIV in two South African regions: the EndoAfrica study.

BACKGROUND: People living with HIV (PLWH) are at risk for cardiovascular disease, but regional differences have not been studied in South Africa. We compared endothelial function and cardiometabolic markers in PLWH and HIV-free controls from two distinct South African regions. METHODS: We measured flow-mediated dilation (FMD), cardiometabolic, immunological and viral markers in age- and gender-matched PLWH on antiretroviral therapy (n = 100/group) and HIV-free participants (n = 50/group) in samples from cohort studies in the North West and Western Cape provinces. RESULTS: Endothelial function and cardiometabolic profiles were not worse in PLWH than in HIV-free individuals, and %FMD was not associated with cardiometabolic, viral or immunological markers. PLWH from the North West region had lower %FMD but overall better metabolic profiles. CONCLUSIONS: Ethnic, cultural and socio-economic differences need further investigation to understand the possible protective role of antiretroviral treatment on the vasculature and to direct region-specific HIV and AIDS guidelines in South Africa.

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.

HIV-related cardiovascular disease: any role for high-density lipoproteins?

The introduction of antiretroviral therapy (ART) has improved the life expectancy of patients infected with human immunodeficiency virus (HIV). However, this population is at an increased risk for noncommunicable diseases, including atherosclerotic cardiovascular disease (CVD). Both ART and viral infection may be potential contributors to the pathophysiology of HIV-related CVD. The mechanisms behind this remain unclear, but it is critical to delineate early biomarkers of cardiovascular risk in the HIV population. In this review, we postulate that potential biomarkers could include alterations to high-density lipoprotein (HDL). Indeed, recent data suggest that HIV and ART may induce structural changes of HDL, thus resulting in shifts in HDL subclass distribution and HDL functionality.

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.

Antiretroviral drug-induced endothelial dysfunction is improved by dual PPARα/γ stimulation in obesity.

Obesity rates are rising in HIV-infected populations; however, the putative role of highly active antiretroviral therapy (HAART) in the development of endothelial and cardiovascular derangements in the presence of pre-existing overweight/obesity is unclear. Although dual peroxisome proliferator-activated receptors-alpha/gamma (PPARα/γ) stimulation mitigates HAART-induced metabolic dysfunction, vascular effects are unresolved. To investigate whether HAART induces vascular dysfunction in obesity and to explore the underlying mechanisms of PPARα/γ stimulation, male Wistar rats were placed on a high-calorie diet for 16 weeks. After 10 weeks, HAART (lopinavir/ritonavir, azidothymidine/lamivudine) with/without PPARα/γ agonist, Saroglitazar, was administered daily for six weeks. Excised thoracic aorta rings were subjected to isometric tension studies and Western blot measurements. HAART+Saroglitazar-treated obese animals recorded lower adiposity indices (4.3 ±â€¯0.5%) vs. HAART only-treated obese rats (5.6 ±â€¯0.3%; p < .01). Maximum acetylcholine-induced vasorelaxation (Rmax), was lower in obese+HAART group (76.10 ±â€¯3.58%) vs. obese control (101.40 ±â€¯4.75%; p < .01). However, Rmax was improved in obese+ HAART+Saroglitazar (101.00 ±â€¯3.12%) vs. obese+HAART rats (p < .001). The mean LogEC50 was improved in obese+HAART+Saroglitazar vs. obese+HAART group; p = .003. Improved endothelial function in obese+ HAART+Saroglitazar group was associated with upregulation of eNOS, PKB/Akt and downregulated p22-phox expression vs. obese+HAART group. Therefore, PPARα/γ stimulation attenuated HAART-induced endothelial dysfunction by upregulating vasoprotective eNOS, PKB/Akt signaling and downregulating pro-oxidative p22-phox expression.