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Analysis of HIV-1 diversity and inflammatory markers in HIV-associated neurocognitive disorders (HAND).
Thesis (PhD)--Stellenbosch University, 2022.
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| Format: | Thesis |
| Language: | en_ZA |
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Stellenbosch : Stellenbosch University
2022
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| _version_ | 1867613980466348032 |
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| access_status_str | Open Access |
| author | Ruhanya, Vurayai |
| author2 | Engelbrecht, Susan |
| author_browse | Engelbrecht, Susan Ruhanya, Vurayai |
| author_facet | Engelbrecht, Susan Ruhanya, Vurayai |
| author_sort | Ruhanya, Vurayai |
| collection | Thesis |
| dc_rights_str_mv | Stellenbosch University |
| description | Thesis (PhD)--Stellenbosch University, 2022. |
| format | Thesis |
| id | oai:scholar.sun.ac.za:10019.1/124577 |
| institution | Stellenbosch University (South Africa) |
| language | en_ZA |
| last_indexed | 2026-06-10T12:44:45.702Z |
| license_str | Other — see source repository |
| provenance_str_mv | Harvested via OAI-PMH from SUNScholar — Stellenbosch University Repository |
| publishDate | 2022 |
| publishDateRange | 2022 |
| publishDateSort | 2022 |
| publisher | Stellenbosch : Stellenbosch University |
| publisherStr | Stellenbosch : Stellenbosch University |
| record_format | dspace |
| source_str | SUNScholar — Stellenbosch University Repository |
| spelling | oai:scholar.sun.ac.za:10019.1/124577 Analysis of HIV-1 diversity and inflammatory markers in HIV-associated neurocognitive disorders (HAND). Ruhanya, Vurayai Engelbrecht, Susan Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Pathology. HIV infections -- Complications Mild cognitive impairment AIDS dementia complex Biochemical markers UCTD Thesis (PhD)--Stellenbosch University, 2022. ENGLISH SUMMARY: HIV-associated neurocognitive disorders (HAND), which involve impairment or disruption of neurocognitive functioning have become one of the most frequent complications in adult HIV-1 infections with global estimates ranging from 42% to 45%. The screening and diagnosis for HAND relies on multiple clinical and neuro-psychometric methods. However, these methods have a low reliability because they are not precise as most of possess inadequate psychometric properties and diagnostic accuracy. Therefore, this study aimed to describe and characterise viral and immunological determinants of HAND and evaluated their relationship with specific clinical, neuromedical and neuropsychological data to identify putative easy-to-measure biological markers for diagnosis of the condition. This study demonstrated that higher peripheral blood lymphocyte-derived HIV-1 proviral DNA is a predictor of global and domain-specific neurocognitive impairment among individuals infected with HIV-1 subtype C. The study also determined proviral load cut-off /threshold value for neurocognitive impairment and associated diagnostic accuracy. It also identified IP-10 and RANTES as a plasma chemokine bio-signature for HIV-associated neurocognitive impairment with diagnostic accuracy comparable to standard psychometric tests used to screen and describe severity of HAND. In addition, the study identified 3 viral genetic signatures for cognitive impairment, namely Lysine at codon 24, (24K) and Arginine at codon 29 (29R) on Tat protein and Tyrosine (Y) at position 45 (45Y) of Vpr. These three signature amino acids were related to classical markers for monitoring HIV infection. Finally, we identified 4 conserved fragment sequences, PEDQGPQREPYNEWTLE (5 to 21), LGQYIY (42 to 47), TYGDTW (49 to 54), PEDQGPQREPYNEW (5 to 18) on viral protein R, that were associated with higher plasma viral load and proviral load. The study has identified novel cytokine/chemokine and viral biomarker signatures for HIV associated neurocognitive impairment with low to moderate diagnostic accuracy. The findings demonstrated a need for interdisciplinary approach to elucidate possible molecular interactions between the peripheral blood immune markers, viral signatures and the CNS that are linked to observed clinical outcomes of neurodegradation in HIV infection. The identified biomarkers can be further investigated for use as screening tools and treatment endpoints for HAND. AFRIKAANS OPSOMMING: MIV-geassosieerde neurokognitiewe versteurings (HAND), wat 'n inkorting of onderbreking van die neurokognitiewe funksionering behels, het een van die mees algemene komplikasies by volwasse MIV-1-infeksies geword, met globale ramings wat wissel van 42% tot 45%. Die sifting en diagnose vir HAND is afhanklik van verskeie kliniese en neuro-psigometriese metodes. Hierdie metodes het egter 'n lae betroubaarheid omdat hulle nie presies is nie, aangesien die meeste onvoldoende psigometriese eienskappe en diagnostiese akkuraatheid het. Daarom was hierdie studie daarop gemik om virale en immunologiese determinante van HAND te beskryf en te karakteriseer en het hulle verband met spesifieke kliniese, neuromediese en neuropsigologiese data geëvalueer om vermeende maklik meetbare biologiese merkers vir die diagnose van die toestand te identifiseer. Hierdie studie het getoon dat perifere bloed limfosiet provirale HIV-1 DNS 'n voorspeller is van neurokognitiewe inkorting onder individue wat met subtipe C-siekte het. Die studie het ook die grens / grenswaarde van die provirale las bepaal vir neurokognitiewe inkorting en gepaardgaande diagnostiese akkuraatheid. Dit word ook geïdentifiseer as 'n chemokien-bio-handtekening vir MIV-geassosieerde neurokognitiewe inkorting met diagnostiese akkuraatheid wat vergelykbaar is met standaard psigometriese toetse wat gebruik word om die erns van HAND te ondersoek en te beskryf. Daarbenewens het die studie drie virale genetiese handtekeninge vir kognitiewe inkorting geïdentifiseer, naamlik Lisien by kodon 24, (24K) en Arginien by kodon 29 (29R) op Tat -proteïen en Tyrosien (Y) op posisie 45 (45Y) van Vpr. Hierdie drie kenmerkende aminosure was verwant aan klassieke merkers vir die monitering van MIV -infeksie. Laastens het ons vier klassieke merkers op virale proteïen R geïdentifiseer, wat verband hou met 'n hoër plasma virale lading en provirale lading. Die studie het nuwe sitokien-/chemokien- en virale biomerker handtekeninge geïdentifiseer vir HIV -geassosieerde neurokognitiewe inkorting met 'n lae tot matige diagnostiese akkuraatheid. Die bevindinge toon 'n behoefte aan 'n interdissiplinêre benadering om moontlike molekulêre interaksies tussen die periferie en die SSS wat verband hou met waargenome kliniese uitkomste van MIV -infeksie, toe te lig. Die geïdentifiseerde biomerkers kan verder ondersoek word vir gebruik as siftings instrumente en eindpunte vir behandeling. Doctoral 2022-01-26T16:07:34Z 2022-04-29T09:20:32Z 2022-01-26T16:07:34Z 2022-04-29T09:20:32Z 2022-04 Thesis http://hdl.handle.net/10019.1/124577 en_ZA Stellenbosch University x, 217 pages : illustrations application/pdf Stellenbosch : Stellenbosch University |
| spellingShingle | HIV infections -- Complications Mild cognitive impairment AIDS dementia complex Biochemical markers UCTD Ruhanya, Vurayai Analysis of HIV-1 diversity and inflammatory markers in HIV-associated neurocognitive disorders (HAND). |
| title | Analysis of HIV-1 diversity and inflammatory markers in HIV-associated neurocognitive disorders (HAND). |
| title_full | Analysis of HIV-1 diversity and inflammatory markers in HIV-associated neurocognitive disorders (HAND). |
| title_fullStr | Analysis of HIV-1 diversity and inflammatory markers in HIV-associated neurocognitive disorders (HAND). |
| title_full_unstemmed | Analysis of HIV-1 diversity and inflammatory markers in HIV-associated neurocognitive disorders (HAND). |
| title_short | Analysis of HIV-1 diversity and inflammatory markers in HIV-associated neurocognitive disorders (HAND). |
| title_sort | analysis of hiv 1 diversity and inflammatory markers in hiv associated neurocognitive disorders hand |
| topic | HIV infections -- Complications Mild cognitive impairment AIDS dementia complex Biochemical markers UCTD |
| url | http://hdl.handle.net/10019.1/124577 |
| work_keys_str_mv | AT ruhanyavurayai analysisofhiv1diversityandinflammatorymarkersinhivassociatedneurocognitivedisordershand |