Doctoral Degrees (Medical Physiology)

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Browsing Doctoral Degrees (Medical Physiology) by Subject "Antiretroviral therapy"

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    The relationship between carotid intima-media thickness, serum biomarkers of cardiovascular disease, and HIV-infection in a South African study population
    (Stellenbosch : Stellenbosch University, 2021-03) Sana, Charania; Strijdom, Hans; Goswami, Nandu; De Boever, Patrick; Cyster, Henry; Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Biomedical Sciences: Medical Physiology.
    Background: Brachial artery flow-mediated dilatation (FMD) and carotid artery intima-media thickness(IMT)are measures of vascular endothelial function and subclinical atherosclerosis respectively. Both endothelial dysfunction and subclinical atherosclerosis have been linked with HIV and antiretroviral therapy (ART) in the developed world. Furthermore, known biomarkers of inflammation and endothelial dysfunction can be measured to predict cardiovascular outcomes in HIV-infected individuals. The exact link between endothelial dysfunction, atherosclerosis, HIV, ART and the biomarkers remains inconclusive, particularly in South African and Western Cape populations.Aims: To investigate the putative relationship between subclinical atherosclerosis, endothelial dysfunction, biomarkers of cardiovascular disease (CVD), and HIV-infection in a Western Cape study population. Methods:Two different epidemiological studies were performed: a cross-sectional main study (HIV-infected, n= 204 of whom on ART n=188and without ART n= 16;and HIV-free, n= 143), and a longitudinal sub-study to assess the 12-month temporal progression of selected CVD outcomes (HIV-free, n= 57). For both studies, participants were recruited from health clinics in Cape Town and Worcester between 2017 and 2018. Lifestyle and health data were collected, and vascular (FMD%and IMT by ultrasound technology), anthropometric (body-mass-index [BMI]; waist circumference [WC]), cardiovascular (lipid profile; blood pressure [BP]; plasma glucose), renal (creatinine; urine albumin creatinine ratio [ACR]), liver (gamma-glutamyl-transferase [GGT]) and HIV-related (viral load; CD4, duration of HIV, duration of treatment) measures were obtained. Serum biomarkers were analyzed using Luminex technology, including C-reactive protein (CRP), tumour necrosis factor-alpha (TNF-α), vascular endothelial growth factor (VEGF), plasminogen activator inhibitor-1 (PAI-1) and adhesion molecules (intercellular adhesion molecule-1 [ICAM-1], vascular cellular adhesion molecule-1 [VCAM-1], e-selectin, p-selectin). Results: In the longitudinal study (mean age: 45 years), WC, plasma glucose, BP, and hypertension, increased at 12-months follow-up. In the cross-sectional study (mean age: 41 years), the HIV-infected group showed a lower BMI, WC, BP,hypertension and PAI-1 versus the HIV-free group (p<0.05), whereas anaemia, ACR, creatinine, GGT and VCAM-1 were increased in the HIV-infected group (p<0.05). Additionally, viral load and VCAM-1 levels were higher in the HIV-infected without ART group versus the ART treated group (p<0.05). CD4 count, total cholesterol, HDL, LDL, hemoglobin, GGT, creatinine levels were higher in the ART group compared to the ART naïve group (p<0.05). Flow mediated dilatation (FMD)was higher and IMT was lower in the ART group versus ART naïve group (p<0.05). Furthermore, no significant correlations were found between biomarkers and FMD and IMT. With regards to independent associations, in the HIV-infected group, age positively associated with IMT (p<0.001), while in the HIV-free group, age, high systolic BP, obesity and LDL cholesterol positively associated with IMT (p<0.05). In the HIV-infected group, ART positively associated, while viral load inversely associated with FMD%. In the HIV-free group, creatinine inversely associated with FMD% (p<0.05).Discussion and conclusion: Overall, our study showed a higher presence and progression of cardiovascular risk parameters in the HIV-free population. In the HIV context, ART showed a morecardioprotective and immune-protective effect, where it was associated with reduced subclinical atherosclerosis and improved endothelial function. Our study confirmed that age is an independent predictor of subclinical atherosclerosis while viral load is an independent, inverse predictor of endothelial function.