Mugwe, Jane Nyambura2020-10-062020-10-062019http://ir-library.ku.ac.ke/handle/123456789/20541A Thesis Submitted In Fulfilment of the Requirements for the Award of the Degree of Doctor of Philosophy (Immunology) In the School of Pure and Applied Sciences of Kenyatta University, November, 2019Cytokines are polypeptides that have a fundamental role in communication within the immune system and in allowing the immune system and host tissue cells to exchange information. They play a central role in the pathogenesis of many diseases including Acquired Immunodeficiency Deficiency Syndrome (AIDS). Cytokines reflect the local or systemic inflammatory milieu, and could serve as predictive biomarkers in Human Immunodeficiency Virus (HIV) infection. Hematological abnormalities are among the most common complications caused by HIV infection and seem to be dependent on the level of virus replication. The aim of this study was to identify circulatory cytokine biomarkers and hematological profiles measureable in blood that could predict the progression of HIV disease in the course of infection. This study was done at the Nakuru Provincial General Hospital (PGH). Eighty individuals were recruited for this study that comprised of forty individuals newly diagnosed with HIV-1 (treatment naïve), twenty HIV negative individuals and twenty HIV positive individuals that were on treatment with highly active antiretroviral therapy (HAART). Hematological parameters were analyzed using hematology auto analyzer system; cytokine types and concentrations were determined by flowcytometry using multiplex cytokine immunoassay and CD4 T cell counts were measured by flowcytometry using Becton and Dickinson Fluorescence Activated Cell Sorter (BD FACS) count. Statistical analysis were done using SPSS version 17. Descriptive statistics were applied; analyses of variance was used to determine the differences in mean circulatory cytokine levels, mean hematological profiles and mean CD4 T cell counts between the subgroups forming the study population. The associations between immunological and hematological profiles were determined. The study found significant differences in the mean Interleukin12p70 (p<0.001), Tumor Necrosis Factor (p<0.05), Interleukin 10 (p<0.05), Interleukin 6 (p<0.005) and Interleukin 1-β (p<0.05) between treatment naïve HIV patients, HIV patients on HAART and HIV negative patients. No significant differences were found between the mean White Blood Cell counts and Red Blood Cell counts (p>0.05) between the treatment naïve HIV patients, HIV negative patients and HIV patients on HAART but there were significant differences between the mean hematocrit (HCT) (p<0.05); hemoglobin (HGB) (p<0.05) and platelets (PLT) (p<0.05). This study also found significant differences in the mean volume of erythrocytes (MCV) (p<0.05), mean content of hemoglobin (MCH) (p<0.05), mean concentration of hemoglobin (MCHC) (p<0.05), mean platelet volume (MPV) (p<0.001), relative width of the distribution of platelets (PDW) (p<0.001) and the absolute content of the mixture of monocytes, basophils and eosinophils (Mid#) (p<0.05). Significant differences in the mean CD4 T cell counts (p<0.001) were observed between the treatments naïve HIV patients, HIV negative patients and HIV patients on HAART. The study found several identical associations between immunological and hematological profiles among the study groups. The study showed that early period of HIV infection is characterized by varying circulatory cytokine levels and could be useful biomarkers and indicators of early immune activation of HIV disease. The results from this study also show that acute HIV infection affects hematological profiles, involving all the blood parameters, some of which may act as indicators of HIV disease progression. The study recommends the use of low cost hematologic tests as biomarkers of disease progression in resource limited settings and also a holistic treatment of HIV infected patients that include supplements to monitor and improve blood parameters and indices in addition to antiretroviral therapy.enThesis