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The haematological profile of a treatment-naïve HIV-positive cohort : a pilot study
Dissertation (MSc (Medical Immunology))--University of Pretoria, 2024.
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| Format: | Thesis |
| Language: | English |
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University of Pretoria
2024
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| _version_ | 1867613678471217152 |
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| access_status_str | Open Access |
| author2 | Durandt, Chrisna |
| author_browse | Durandt, Chrisna |
| author_facet | Durandt, Chrisna |
| collection | Thesis |
| dc_rights_str_mv | © 2023 University of Pretoria. All rights reserved. The copyright in this work vests in the University of Pretoria. No part of this work may be reproduced or transmitted in any form or by any means, without the prior written permission of the University of Pretoria. |
| description | Dissertation (MSc (Medical Immunology))--University of Pretoria, 2024. |
| format | Thesis |
| id | oai:repository.up.ac.za:2263/97288 |
| institution | University of Pretoria (South Africa) |
| language | English |
| last_indexed | 2026-06-10T12:39:58.102Z |
| license_str | Other — see source repository |
| provenance_str_mv | Harvested via OAI-PMH from UPSpace — University of Pretoria Institutional Repository |
| publishDate | 2024 |
| publishDateRange | 2024 |
| publishDateSort | 2024 |
| publisher | University of Pretoria |
| publisherStr | University of Pretoria |
| record_format | dspace |
| source_str | UPSpace — University of Pretoria Institutional Repository |
| spelling | oai:repository.up.ac.za:2263/97288 The haematological profile of a treatment-naïve HIV-positive cohort : a pilot study Durandt, Chrisna tsungaimash@icloud.com Mellet, Juanita Moodley, Vanessa Mashingaidze, Tsungai Vesta UCTD HIV Haematopoieisis Treatment-naïve Cytopenia Circulating HSPCs HIV-positive Sustainable Development Goals (SDGs) SDG-03: Good health and well-being Health Sciences theses SDG-03 Dissertation (MSc (Medical Immunology))--University of Pretoria, 2024. Human immunodeficiency virus (HIV) infection has been observed to significantly impact both the immune system and haematopoiesis. Haematopoiesis is the regulated process of producing the cellular components of blood with the haematopoietic stem and progenitor cells (HSPCs) as the cells of origin. Haematopoiesis occurs mainly in the bone marrow (BM). Haematopoietic stem and progenitor cells are necessary for the maintenance of steady-state haematopoiesis and a fully functional immune system. In HIV-negative individuals, it has been noted that a small proportion of HSPCs consistently migrate from the BM into the peripheral circulation. Under stress conditions such as infection with HIV, steady-state haematopoiesis is disrupted, and downstream HSPC differentiation activity becomes dysregulated. Literature reports that dysregulated HSPC differentiation leads to increased levels of the immunosuppressive myeloid-derived suppressor cells (MDSCs) in HIV infection, with no evidence of MDSCs in healthy individuals. To better understand this disruption, we investigated whether a link exists between the immature circulating HSPCs, heterogeneous MDSCs, and the haematological profile of treatment-naïve HIV-positive and HIV-negative (control) groups, respectively. This was performed using peripheral blood donated by consenting treatment-naïve HIV-positive and HIV-negative (control) participants. The frequency and phenotype of the circulating HSPCs in a treatment-naïve HIV-positive cohort was determined and compared to an HIV-negative (control) cohort using flow cytometry. This study found a significant decrease in circulating HSPCs in the treatment-naïve HIV-positive group in comparison to the HIV-negative (control) group with no difference in the phenotype between the two groups. Furthermore, HIV-mediated disruption of haematopoiesis often results in haematological abnormalities, such as cytopenias. Cytopenias arising from HIV infection are associated with increased morbidity and mortality. A full blood count with a white cell differential was performed to investigate the extent of the disruption. We observed anaemia and thrombocytopenia within the HIV-positive group. Neither leukopenia nor neutropenia were observed in this study. Additionally, significant reductions were observed in the white and red cell counts, haemoglobin, and absolute neutrophil counts among the HIV-positive group, in comparison to the HIV-negative (control) group. The exact mechanism of HIV-mediated cytopenias is not clear, but scientific evidence strongly suggests that HIV disrupts the BM milieu which impacts on the function of HSPCs. Therefore, the functionality of circulating HSPCs were also investigated with the colony forming unit (CFU) assay. The HSPCs differentiated to produce CFU-granulocyte, erythrocytes, monocyte, megakaryocyte (GEMM), CFU-granulocyte, monocyte (GM), and burst forming units-erythrocyte (BFU-E). No phenotypic differences were observed between HIV-positive and HIV-negative (control) cohorts. However, when investigating the impact of HIV on the immune system using flow cytometry, various immune cell populations, including the cluster of differentiation (CD)4+ T cells were significantly decreased in the HIV-positive group when compared to the HIV-negative (control) group. Whereas the CD8+ T cells were significantly increased in the HIV-positive group compared to the HIV-negative (control) group. Furthermore, this study did not observe increased levels of MDSCs in the HIV-positive group as hypothesised. In summary, the study observed decreased frequencies of circulating HSPCs, which is indicative of abnormal haematopoiesis and subsequent BM disruption. The BM disruption trickles down into haematological indices and supports the onset of cytopenias. National Research Foundation Poliomyelitis Research Foundation University of Pretoria Immunology MSc (Medical Immunology) Unrestricted Faculty of Health Sciences 2024-07-29T12:49:52Z 2024-07-29T12:49:52Z 2025-04 2024 Dissertation * http://hdl.handle.net/2263/97288 https://doi.org/10.25403/UPresearchdata.26371105 en © 2023 University of Pretoria. All rights reserved. The copyright in this work vests in the University of Pretoria. No part of this work may be reproduced or transmitted in any form or by any means, without the prior written permission of the University of Pretoria. application/pdf University of Pretoria |
| spellingShingle | UCTD HIV Haematopoieisis Treatment-naïve Cytopenia Circulating HSPCs HIV-positive Sustainable Development Goals (SDGs) SDG-03: Good health and well-being Health Sciences theses SDG-03 The haematological profile of a treatment-naïve HIV-positive cohort : a pilot study |
| title | The haematological profile of a treatment-naïve HIV-positive cohort : a pilot study |
| title_full | The haematological profile of a treatment-naïve HIV-positive cohort : a pilot study |
| title_fullStr | The haematological profile of a treatment-naïve HIV-positive cohort : a pilot study |
| title_full_unstemmed | The haematological profile of a treatment-naïve HIV-positive cohort : a pilot study |
| title_short | The haematological profile of a treatment-naïve HIV-positive cohort : a pilot study |
| title_sort | haematological profile of a treatment naive hiv positive cohort a pilot study |
| topic | UCTD HIV Haematopoieisis Treatment-naïve Cytopenia Circulating HSPCs HIV-positive Sustainable Development Goals (SDGs) SDG-03: Good health and well-being Health Sciences theses SDG-03 |
| url | http://hdl.handle.net/2263/97288 https://doi.org/10.25403/UPresearchdata.26371105 |