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The effect of dolutegravir on adipose tissue health
Thesis (MSc) -- 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_ | 1867613975206690816 |
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| access_status_str | Open Access |
| author | Coetzee, Johanna Adriana |
| author2 | Smith, Carine |
| author_browse | Coetzee, Johanna Adriana Smith, Carine |
| author_facet | Smith, Carine Coetzee, Johanna Adriana |
| author_sort | Coetzee, Johanna Adriana |
| collection | Thesis |
| dc_rights_str_mv | Stellenbosch University |
| description | Thesis (MSc) -- Stellenbosch University, 2022. |
| format | Thesis |
| id | oai:scholar.sun.ac.za:10019.1/125913 |
| institution | Stellenbosch University (South Africa) |
| language | en_ZA |
| last_indexed | 2026-06-10T12:44:41.084Z |
| 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:10019.1/125913 The effect of dolutegravir on adipose tissue health Coetzee, Johanna Adriana Smith, Carine Ross, Kelly Shirley Faculty of Medicine and Health Sciences. Dept. of Medicine. Division of Clinical Pharmacology. Adipose tissues – Health HIV (Viruses) Antiretroviral agents Inflammation -- Alternative treatment Cytokines -- Therapeutic use UCTD Thesis (MSc) -- Stellenbosch University, 2022. ENGLISH ABSTRACT: Introduction: Dolutegravir, an integrase strand transfer inhibitor (INSTI), forms part of the first-line antiretroviral (ARV) therapy. Despite low cost, fewer drug-drug interactions and minimal reported side effects, dolutegravir use has clinically been associated with weight gain. The significance of this in terms of adipose- and overall patient health remains to be fully elucidated. Methods: The effects of dolutegravir on the adipose tissue health were assessed in a 12-week treatment intervention study in Wistar rats, allowing an assessment of risk profile for dolutegravir in the absence of potential confounding effects of retroviral infection or other ARV agents commonly found in combination therapy. Dolutegravir was administered as a human equivalent dose set in jelly blocks, once daily for 12 weeks, starting at 8 weeks of age. Visceral adipose tissue morphology and fibrosis profile, adipokine and inflammatory cytokine levels were assessed. Results: Dolutegravir did not change the rate of body mass increase in the rats (when compared to a placebo group). Females presented to have smaller adipocyte size and increased adiponectin secretion – more pronounced in the treated group compared to the controls. While pro-inflammatory cytokines (TNF-α and MCP-1) were also elevated in both the female groups compared to the males. Conclusion: Current data illustrates that in terms of potential effects of dolutegravir on AT health, females seem more vulnerable to undesired longer term outcome. The overall small effect sizes seen is in line with a chronic, low-grade dysregulation which may predispose dolutegravir-treated patients to development of co-morbidities with a chronic inflammatory character. AFRIKAANS OPSOMMING: Inleiding: Dolutegravir (DTG), is onlangs ingesluit as deel van die voorlyn antiretroviralemiddels op die mark. Ten spyte van laer kostes, verlaagde risiko van interaksie met ander medikasie en ‘n afname in geraporteerde neweeffekte, word die gebruik van DTG steed geassosieer met merkbare gewigstoename. Gewigstoename gaan gepaard met lae graadse lokale en sistemiese inflammasie - Van daar die belangom die effek van die DTG en DTG verwante gewigstoename in vetweefsel, en die gesondheid van individue te evalueer. Metodes: Die effek van DTG op vetweefsel is geavalueer deur middel van ‘n 12-week rotstudie.Die studie het bestaan uit 24 Rotte – wat uit 12 vroulik en 12 manlike diere bestaan het. Die rotte is verder opgedeel in ‘n groep wat DTG belandeling ontvang het en ‘n kontrole groep (Die kontrole groep het fopmedikasie (placebo) ontvang). Die DTG is in ‘n jellieblokkie gestol en daagliks vir die rotte gevoer. Die dosis was ekwiwalent aan die eens-daaglikse dosis wat pasiënte met MIV ontvang. Die studie is gedoen in die afwesigheid van MIV en kombinasie antiretroviralemiddels om die effekte wat deur DTG veroosaak word optimaal en noukeurig vas te stel. Viserale vet is gebruik om die morfologie en fibrose indeks te ondersoek. Verder is die vlakke van verskillende pro-inflammatoriese merkers (TNFα, MCP-1 ens.) in die vet gemeet. Resultate: Vanuit die resultate verkry met die afhandel van die studie is daar geen gewigs toename opgemerk nie. In die vetweefsel van die vroulike diere is daar opmerklik kleiner selle met ‘n duidelike verhoogde adiponectin vlakke waargeneem wanneer dit met sitokien vlakke in die vet weefsel van die manlike diere vergelyk word. Terselfdetyd was die pro-inflammatoriese merkers -TNFα en MCP1 – ook in die vet weefsel van die vroulike diere verhoog in vergelyking met die van die manlike diere. Gevolgtrekking: Saamgevat wys die data gegenireer vanuit die studie dat DTG moontlik vetweefsel gesondheid negatief beinvloed. Dit stel ook voor dat die vroulike geslag meer vatbaar is vir ongewensde langtermyn uitkomste. Die kleiner vetselle wat in die vetweefsel waargeneem word is in lyn met die moontlike aandeel wat DTG het in kroniese lae-graadse inflammasie – dit maak patiente wat DTG-behandeling ontvang meer vatbaar vir comorbiditeite wat kroniese inflammasie as kenmerk het. Masters 2022-10-12T10:26:41Z 2023-01-16T12:41:02Z 2022-10-12T10:26:41Z 2023-01-16T12:41:02Z 2022-10 Thesis http://hdl.handle.net/10019.1/125913 en_ZA Stellenbosch University xi, 81 pages : illustrations application/pdf Stellenbosch : Stellenbosch University |
| spellingShingle | Adipose tissues – Health HIV (Viruses) Antiretroviral agents Inflammation -- Alternative treatment Cytokines -- Therapeutic use UCTD Coetzee, Johanna Adriana The effect of dolutegravir on adipose tissue health |
| title | The effect of dolutegravir on adipose tissue health |
| title_full | The effect of dolutegravir on adipose tissue health |
| title_fullStr | The effect of dolutegravir on adipose tissue health |
| title_full_unstemmed | The effect of dolutegravir on adipose tissue health |
| title_short | The effect of dolutegravir on adipose tissue health |
| title_sort | effect of dolutegravir on adipose tissue health |
| topic | Adipose tissues – Health HIV (Viruses) Antiretroviral agents Inflammation -- Alternative treatment Cytokines -- Therapeutic use UCTD |
| url | http://hdl.handle.net/10019.1/125913 |
| work_keys_str_mv | AT coetzeejohannaadriana theeffectofdolutegravironadiposetissuehealth AT coetzeejohannaadriana effectofdolutegravironadiposetissuehealth |