Masters Degrees (Medical Physiology)

Permanent URI for this collection

https://scholar.sun.ac.za/handle/10019.1/3553

Browse

Browsing Masters Degrees (Medical Physiology) by Author "Charania, Sana"

Now showing 1 - 1 of 1
  • Thumbnail Image
    Item
    Investigating the effects of first line and second line antiretroviral drugs on HIV exposed endothelial function - A clinical study, supported by a mechanistic in-vitro approach
    (Stellenbosch : Stellenbosch University, 2017-03) Charania, Sana; Strijdom, Hans; Genis, Amanda; Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Biomedical Sciences: Medical Physiology
    ENGLISH ABSTRACT : Background: There is an interaction between HIV, antiretroviral treatment (ART) and endothelial dysfunction; furthermore, HIV-infected individuals (± ART) show an increased incidence of cardiovascular risk factors. However, the evidence stems mainly from studies in developed countries with a paucity of data on these interactions in the South African context. Aims: To investigate the effects of first line and second line ART on HIV exposed vascular endothelial function, in a clinical and in vitro setting. Methods: In the clinical study, participants were recruited in Worcester and allocated to one of four study groups: HIV-negative, HIV-positive ART naïve, HIV-positive first line ART and HIV-positive second line ART. Data were collected via health questionnaires, anthropometric assessments, blood pressure measurements, brachial artery flow mediated dilatation (FMD) and blood chemistry analyses (C-reactive protein (CRP), fasting glucose, HbA1c, total cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides, as well as CD4 count and viral load in HIV-infected individuals). For the in vitro sub-study, a conditioned growth medium was developed containing HIV-related proteins in which aortic endothelial cells (AECs) were incubated. Additionally, AECs were treated with first and second ART drugs. End-points were nitric oxide (NO) production, cell viability and ROS production measured by flow cytometric analysis. Results: There were no inter-group differences with regard to FMD. The median BMI and waist circumference measurements were lower in the HIV-positive groups versus HIV-negative (p < 0.05). Median total cholesterol levels were lower (p < 0.05) in the HIV-positive ART groups versus HIV-negative, and higher in the HIV-positive first line ART group versus the ART naïve group (p< 0.05). Furthermore, mean LDL-cholesterol levels were lower in all HIV-positive groups versus HIV-negative (p< 0.05). Median HBA1C% values were lower in the HIV-positive second line ART versus ART-naïve group (p < 0.05). Regression analyses showed that smoking in first line ART, and CRP and CD4 levels in second line ART were negatively associated with FMD%. In the in vitro sub-study, the HIV-1 gp160 protein was identified in the HIV-conditioned medium. No effects were observed in HIV-conditioned medium treated AECs. In the first and second line ART dose-response investigations, it was found that double first line drug concentration and normal second line drug concentration exerted no harmful effects on AECs. Discussion and Conclusion: Clinical data suggested that the cardiovascular risk profile appeared to be more favourable in HIV-positive groups versus HIV-negative. There were no inter-group differences in terms of endothelial function (FMD). CD4 and CRP, as well as female gender were independent predictors of vascular endothelial function in the HIV-positive second line ART group. Furthermore, smoking was found to be a negative independent predictor of endothelial function in the HIV-positive first line ART group. The in vitro findings showed that the HIV-conditioned medium protocol successfully resulted in the expression of the HIV-1 gp160 protein; however, the conditioned medium failed to induce injury. In the ART dose-response investigations, the double drug concentration for first line ART and normal drug concentration for second line ART, could be considered a safe concentration to use in future investigations.