Biochemical Markers of Oxidative Stress as Indices of HIV/AIDS Progression

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Reactive Oxygen Species (ROS) has been implicated in the pathogenesis and the progression of HIV infection. This study was aimed at investigating the levels of oxidative stress and their probable relationship as markers of HIV disease progression in HIV positive patients in two established HIV/ART centres in Ghana. In all two hundred and twenty eight (228) confirmed People Living with HIV/AIDS (PLWHAs) were included in the study. The subjects were recruited from the Central Regional Hospital (CRH) and Bolgatanga Regional Hospital (BRH). One hundred and forty-three (143; 62.72%) PLWHAs were recruited from CRH and they comprised of eighty one (81; 56.64%) males and sixty two (62; 43.36%) females whilst eighty five (85; 37.28%) PLWHAs were recruited from BRH comprising of forty three (43; 50.59%) males and forty two (42; 49.41%) females. These two hospitals were chosen to give a fair representation of PLWHAs in Ghana. Another 100 sex- and age-matched healthy, HIV-seronegative individuals were studied in parallel as controls. Ethical clearance was obtained from Committee on Human Research, Publications and Ethics (CHRPE), School of Medical Sciences, Kwame Nkrumah University of Science & Technology (KNUST), Kumasi. All subjects gave informed consent to take part in the study after verbal and written explanation of the methods and risks involved had been given. Venous blood samples were taken and assayed for the haematological parameters (haemoglobin (Hb), haematocrit (HCT) and total white blood cell count (WBC), biochemical assays (total Serum Protein, Serum Albumin, Triglycerides, Total Cholesterol, HDL-cholesterol and LDL-cholesterol and markers of oxidative stress (Serum Malondialdehyde (MDA), Ferric Reducing Ability of Plasma (FRAP) and serum Vitamin C and E, Superoxide Dismutase (SOD) Glutathione Peroxidase (GPx). The subjects with the mean age of 36.9±10.9 years which was not significantly different from that of the control group of 39.4+13.4 years. The PLWHAs subjects were grouped per the criteria of the Center for Disease Control (CDC) as: CD4 count (1) ≥ 500 mm-3; (2) 200 – 499 mm-3; and (3) < 200 mm-3. Forty three (43; 18.86%) patients (38.7+10.94 years) had a CD4+ count ≥ 500 mm-3, sixty three (63; 27.63%) patients (37.4+9.54 years) had a CD4+ count between 200 – 499 mm-3 and one hundred and twenty two (122; 53.51%) patients (36.7+10.93 years) had a CD4+ count < 200 mm-3. Markers of oxidative stress revealed significant differences between the patients and control subjects. Malondialdehyde (p<0.001) in the patients was markedly increased as compared to the control group. This suggests increased lipid peroxidation in HIV infected individuals and this increased with the progression of the infection. Ferric reducing ability of Plasma (p<0.0001), Glutathione peroxidase (p<0.0001), Superoxide Dismutase (p<0.0001) were decreased in the patients compared to the control group indicating an increase in free radicals product. Vitamin C (p<0.0001) and E (p<0.0001) were reduced in the patients compared to the control group suggesting a decrease in the antioxidant level as the HIV infection progressed in the patients. Results from the haematological assay revealed a significant decrease in the mean blood haemoglobin levels of the HIV positive patients compared to the control subjects. The significant positive correlation (p<0.0001) between Hb and CD4 count highlights its usefulness in the progression of HIV infection. The haematocrit result pattern showed a consistency with the Hb. There was a significant positive correlation between HCT and CD4 counts (p<0.0001). No significant difference was observed in the total white blood cell count (WBC) of HIV positive patients and the control group (p=0.1830). Apart from serum total Protein (p<0.0001) and Triglycerides (p<0.001), which showed significant increase as compared to the control group, serum albumin (p=0.0106), Total cholesterol (p<0.0001), HDL-cholesterol (p<0.0001) and LDL cholesterol (p<0.0001) showed a significant decrease as compared to the control group. From the correlation analysis, serum Albumin(R=0.41), Total cholesterol (R=0.67), HDL-cholesterol (R=0.27) and LDL cholesterol (R=0.27) showed a positive significant correlation in relation to the CD4 count. However serum total Protein (R=-0.36), Potassium (R=-0.67) and Triglycerides (R=-0.27) did show a negative correlation in relation to the CD4 count. Altogether the findings of this study have revealed that oxidative stress increases as HIV infection progressed. We propose from the study that the interaction of the mechanism underlying oxidative stress and HIV progression and subsequent apoptosis is a receptor-mediated process. During the early phase of HIV infection, generation of ROS has been known to activate HIV replication in vivo through the activation of a factor that binds to a DNA-binding protein, NF-kappa B which is a known activator of HIV replication. This leads to increase in the disturbance in the antioxidant system leading to an increase in ROS production with concomitant biochemical and haematological derangement as observed in the study. Therefore an early intervention with antioxidant supplements in the early phase of HIV infection is likely to reduce HIV progression and improve the immune function.
A Thesis Submitted in Partial Fulfillment Of the Requirement for the Degree Of DOCTOR OF PHILOSOPHY in the Department of Molecular Medicine, School of Medical Sciences,