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Efavirenz pharmacogenetics and metabolic toxicity in black South Africans

Background: Efavirenz is associated with hepatotoxicity, dyslipidaemia and dysglycaemia. We aimed to determine if CYP2B6 composite metaboliser genotypes influence lipids, glucose and ALT concentrations. Methods: Data and DNA from South African antiretroviral therapy (ART)-naïve participants initiati...

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Main Author: Makgai, Lesiba Meshack
Other Authors: Sinxadi, Phumla Z
Format: Thesis
Language:English
Published: Department of Medicine 2023
Subjects:
Clinical Pharmacology
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access_status_str Open Access
author Makgai, Lesiba Meshack
author2 Sinxadi, Phumla Z
author_browse Makgai, Lesiba Meshack
Sinxadi, Phumla Z
author_facet Sinxadi, Phumla Z
Makgai, Lesiba Meshack
author_sort Makgai, Lesiba Meshack
collection Thesis
description Background: Efavirenz is associated with hepatotoxicity, dyslipidaemia and dysglycaemia. We aimed to determine if CYP2B6 composite metaboliser genotypes influence lipids, glucose and ALT concentrations. Methods: Data and DNA from South African antiretroviral therapy (ART)-naïve participants initiating efavirenz with emtricitabine plus tenofovir disoproxil fumarate (TDF) were used to characterise associations between CYP2B6 metaboliser genotypes and the percentage difference in metabolic parameters from baseline to week 48 using univariate and multivariate linear regression models. Results: A total of 171 participants were successfully genotyped. Median baseline age was 32 years, CD4 count was 292 cells/mm3 and log10 viral load was 4.42 copies/ml. Univariate analyses showed significant associations between CYP2B6 slow metaboliser genotype and total cholesterol (β = 13.78, p = 0.003), LDL cholesterol (β = 15.89, p = 0.008) and HDL cholesterol (β = 24.78, p = 0.002). These associations remained significant in multivariate analyses adjusting for age, sex, weight, baseline CD4 cell count and viral load [total cholesterol (β = 14.93, p< 0.001), LDL cholesterol (β = 15.57, p = 0.014), and HDL cholesterol (β = 24.22, p< 0.001)]. No associations were found between CYP2B6 metaboliser genotype and triglycerides, glucose or ALT. Conclusion: Among Black South African participants on efavirenz-based ART, CYP2B6 slow metaboliser genotype was associated with high cholesterol concentrations. In an African population with high prevalence of CYP2B6 slow metabolisers, close monitoring of lipids is needed.
format Thesis
id oai:open.uct.ac.za:11427/37486
institution University of Cape Town (South Africa)
language eng
last_indexed 2026-06-10T12:32:24.523Z
license_str Not specified — see source repository
provenance_str_mv Harvested via OAI-PMH from UCTD — University of Cape Town Open Access Repository
publishDate 2023
publishDateRange 2023
publishDateSort 2023
publisher Department of Medicine
publisherStr Department of Medicine
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source_str UCTD — University of Cape Town Open Access Repository
spelling oai:open.uct.ac.za:11427/37486 Efavirenz pharmacogenetics and metabolic toxicity in black South Africans Makgai, Lesiba Meshack Sinxadi, Phumla Z Maartens, Gary Clinical Pharmacology Background: Efavirenz is associated with hepatotoxicity, dyslipidaemia and dysglycaemia. We aimed to determine if CYP2B6 composite metaboliser genotypes influence lipids, glucose and ALT concentrations. Methods: Data and DNA from South African antiretroviral therapy (ART)-naïve participants initiating efavirenz with emtricitabine plus tenofovir disoproxil fumarate (TDF) were used to characterise associations between CYP2B6 metaboliser genotypes and the percentage difference in metabolic parameters from baseline to week 48 using univariate and multivariate linear regression models. Results: A total of 171 participants were successfully genotyped. Median baseline age was 32 years, CD4 count was 292 cells/mm3 and log10 viral load was 4.42 copies/ml. Univariate analyses showed significant associations between CYP2B6 slow metaboliser genotype and total cholesterol (β = 13.78, p = 0.003), LDL cholesterol (β = 15.89, p = 0.008) and HDL cholesterol (β = 24.78, p = 0.002). These associations remained significant in multivariate analyses adjusting for age, sex, weight, baseline CD4 cell count and viral load [total cholesterol (β = 14.93, p< 0.001), LDL cholesterol (β = 15.57, p = 0.014), and HDL cholesterol (β = 24.22, p< 0.001)]. No associations were found between CYP2B6 metaboliser genotype and triglycerides, glucose or ALT. Conclusion: Among Black South African participants on efavirenz-based ART, CYP2B6 slow metaboliser genotype was associated with high cholesterol concentrations. In an African population with high prevalence of CYP2B6 slow metabolisers, close monitoring of lipids is needed. 2023-03-17T11:58:16Z 2023-03-17T11:58:16Z 2022 2023-03-17T08:41:53Z Master Thesis Masters MPhil http://hdl.handle.net/11427/37486 eng application/pdf Department of Medicine Faculty of Health Sciences
spellingShingle Clinical Pharmacology
Makgai, Lesiba Meshack
Efavirenz pharmacogenetics and metabolic toxicity in black South Africans
thesis_degree_str Master's
title Efavirenz pharmacogenetics and metabolic toxicity in black South Africans
title_full Efavirenz pharmacogenetics and metabolic toxicity in black South Africans
title_fullStr Efavirenz pharmacogenetics and metabolic toxicity in black South Africans
title_full_unstemmed Efavirenz pharmacogenetics and metabolic toxicity in black South Africans
title_short Efavirenz pharmacogenetics and metabolic toxicity in black South Africans
title_sort efavirenz pharmacogenetics and metabolic toxicity in black south africans
topic Clinical Pharmacology
url http://hdl.handle.net/11427/37486
work_keys_str_mv AT makgailesibameshack efavirenzpharmacogeneticsandmetabolictoxicityinblacksouthafricans

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