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Is mitochondrial dysfunction a putative marker of cardiometabolic disease in people living with HIV?
Mokoena, K. 2025. Is mitochondrial dysfunction a putative marker of cardiometabolic disease in people living with HIV? Unpublished masters thesis. Stellenbosch: Stellenbosch University [online]. Available: https://scholar.sun.ac.za/items/18e3a6ac-5237-49e5-bc6c-4bc507a44998
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| Language: | English |
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Stellenbosch : Stellenbosch University
2025
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| _version_ | 1867613769284190208 |
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| access_status_str | Open Access |
| author | Mokoena, Kheya Reatlegile |
| author2 | Strijdom, Hans |
| author_browse | Mokoena, Kheya Reatlegile Strijdom, Hans |
| author_facet | Strijdom, Hans Mokoena, Kheya Reatlegile |
| author_sort | Mokoena, Kheya Reatlegile |
| collection | Thesis |
| dc_rights_str_mv | Stellenbosch University |
| description | Mokoena, K. 2025. Is mitochondrial dysfunction a putative marker of cardiometabolic disease in people living with HIV? Unpublished masters thesis. Stellenbosch: Stellenbosch University [online]. Available: https://scholar.sun.ac.za/items/18e3a6ac-5237-49e5-bc6c-4bc507a44998 |
| format | Thesis |
| id | oai:scholar.sun.ac.za:10019.1/132250 |
| institution | Stellenbosch University (South Africa) |
| language | English |
| last_indexed | 2026-06-10T12:41:24.431Z |
| license_str | Other — see source repository |
| provenance_str_mv | Harvested via OAI-PMH from SUNScholar — Stellenbosch University Repository |
| publishDate | 2025 |
| publishDateRange | 2025 |
| publishDateSort | 2025 |
| publisher | Stellenbosch : Stellenbosch University |
| publisherStr | Stellenbosch : Stellenbosch University |
| record_format | dspace |
| source_str | SUNScholar — Stellenbosch University Repository |
| spelling | oai:scholar.sun.ac.za:10019.1/132250 Is mitochondrial dysfunction a putative marker of cardiometabolic disease in people living with HIV? Mokoena, Kheya Reatlegile Strijdom, Hans Webster, Ingrid Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Biomedical Sciences. Division of Medical Physiology. Mitochondrial pathology -- South Africa HIV infections -- Complications -- South Africa Cardiovascular system -- Diseases -- South Africa HIV-positive persons -- Health and hygiene -- South Africa UCTD Mokoena, K. 2025. Is mitochondrial dysfunction a putative marker of cardiometabolic disease in people living with HIV? Unpublished masters thesis. Stellenbosch: Stellenbosch University [online]. Available: https://scholar.sun.ac.za/items/18e3a6ac-5237-49e5-bc6c-4bc507a44998 Thesis (MSc)--Stellenbosch University, 2025. ENGLISH ABSTRACT: Background and Aim: Cardiometabolic disease (CMD) in people living with HIV (PLWH) represents a global concern. HIV-related viral factors and antiretroviral therapy have been previously shown to cause mitochondrial dysfunction, however, the role played by mitochondria in HIV-associated CMD is poorly described, especially in Sub-Saharan Africa. This exploratory study examined the relationships between mitochondrial function, HIV status, and CMD within a South African cohort. Methods: This cross-sectional study consisted of 158 participants, recruited from a healthcare clinic in Worcester (Western Cape). The two main study groups (HIV- and HIV+) were further divided into HIV- with (n=39) and without CMD (n=33), and HIV+ with (n=44) and without CMD (n=42). Demographic, socioeconomic, medical data and anthropometric data were collected. Blood and urine samples were collected for biochemical analysis and for isolating peripheral blood mononuclear cells for mitochondrial analysis via high-resolution respirometry (Oroboros®). CMD was defined as having 3 or more of a pre-determined set of cardiovascular and metabolic risk factors. Data were statistically analysed with SPSS Version 29.0(241) software. Results: The cohort was relatively young (<42 years) and consisted mostly of women (HIV-: 70.8%, HIV+: 77.9%), with high smoking rates. Liver fibrosis marker (FIB-4: 0.945 [0.19-4.19] vs. 0.605 [0.20-4.04], p<0.001) was higher in HIV+. Routine respiration (O2 consumption: pmol/s/mL) was significantly lower in the HIV+ group vs. HIV- [0.001 (0.001-5.767) vs. 1.694 (0.001-8.050), p<0.001], and positively associated with HbA1c [Standardised β (95%CI): [0.285 (0.030-0.540, p=0.029], whereas residual oxygen consumption (ROX) was higher in HIV+ vs. HIV- [0.312 (0.001-6.330) vs. 0.157 (0.001-4.798), p=0.036]. Routine respiration (H2O2 production: μM) was associated with smoking status [β: 0.335 (0.081-0.590, p=0.011] and HIV duration <10 years [β: 0.311 (0.038-0.584, p=0.026], and inversely associated with FIB-4 [β: -0.470 (-0.769 to -0.171, p=0.011]. The adjusted marginal mean for cytochrome c response (O2 consumption: pmol/s/mL) was lower in HIV+ (0.178 [0.084-0.271] vs. 0.340 [0.237-0.442], p=0.030). Maximal ETS capacity (O2 consumption: pmol/s/mL) was negatively associated with CMD+ status [β: -0.340 (-0.631 to -0.050, p=0.022]. Discussion and conclusion: The findings of our study point to a greater degree of altered mitochondrial function in PLWH compared to their HIV–negative control counterparts, with particular reference to overall mitochondrial health (lower routine respiration), loss of outer membrane integrity (lower cytochrome c response) and increased oxidative side reactions (elevated ROX). H2O2 production was also altered at a number of mitochondrial states. In addition to changes observed between PLWH and HIV-, mitochondrial function was affected by CMD status at some respiratory states. Regression models furthermore demonstrated a number of associations between markers of CMD, HIV duration, and mitochondrial respiratory states in terms of both O2 consumption and H2O2 production. In conclusion, the results of this exploratory study suggest that mitochondrial function may be altered in PLWH and CMD. Our study may pave the way for future longitudinal studies with more diverse and larger cohorts to provide stronger evidence of a role for altered mitochondrial function in PLWH. This could benefit the management of PLWH at risk of mitochondrial dysfunction and CMD. AFRIKAANSE OPSOMMING: Geen opsomming beskikbaar. Masters 2025-05-30T13:46:57Z 2025-05-30T13:46:57Z 2025-03 Thesis https://scholar.sun.ac.za/handle/10019.1/132250 en Stellenbosch University 137 pages : illustrations application/pdf Stellenbosch : Stellenbosch University |
| spellingShingle | Mitochondrial pathology -- South Africa HIV infections -- Complications -- South Africa Cardiovascular system -- Diseases -- South Africa HIV-positive persons -- Health and hygiene -- South Africa UCTD Mokoena, Kheya Reatlegile Is mitochondrial dysfunction a putative marker of cardiometabolic disease in people living with HIV? |
| title | Is mitochondrial dysfunction a putative marker of cardiometabolic disease in people living with HIV? |
| title_full | Is mitochondrial dysfunction a putative marker of cardiometabolic disease in people living with HIV? |
| title_fullStr | Is mitochondrial dysfunction a putative marker of cardiometabolic disease in people living with HIV? |
| title_full_unstemmed | Is mitochondrial dysfunction a putative marker of cardiometabolic disease in people living with HIV? |
| title_short | Is mitochondrial dysfunction a putative marker of cardiometabolic disease in people living with HIV? |
| title_sort | is mitochondrial dysfunction a putative marker of cardiometabolic disease in people living with hiv |
| topic | Mitochondrial pathology -- South Africa HIV infections -- Complications -- South Africa Cardiovascular system -- Diseases -- South Africa HIV-positive persons -- Health and hygiene -- South Africa UCTD |
| url | https://scholar.sun.ac.za/handle/10019.1/132250 |
| work_keys_str_mv | AT mokoenakheyareatlegile ismitochondrialdysfunctionaputativemarkerofcardiometabolicdiseaseinpeoplelivingwithhiv |