Efavirenz pharmacogenetics and metabolic toxicity in black South Africans
| dc.contributor.advisor | Sinxadi, Phumla Z | |
| dc.contributor.advisor | Maartens, Gary | |
| dc.contributor.author | Makgai, Lesiba Meshack | |
| dc.date.accessioned | 2023-03-17T11:58:16Z | |
| dc.date.available | 2023-03-17T11:58:16Z | |
| dc.date.issued | 2022 | |
| dc.date.updated | 2023-03-17T08:41:53Z | |
| dc.description.abstract | 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. | |
| dc.identifier.apacitation | Makgai, L. M. (2022). <i>Efavirenz pharmacogenetics and metabolic toxicity in black South Africans</i>. (). ,Faculty of Health Sciences ,Department of Medicine. Retrieved from http://hdl.handle.net/11427/37486 | en_ZA |
| dc.identifier.chicagocitation | Makgai, Lesiba Meshack. <i>"Efavirenz pharmacogenetics and metabolic toxicity in black South Africans."</i> ., ,Faculty of Health Sciences ,Department of Medicine, 2022. http://hdl.handle.net/11427/37486 | en_ZA |
| dc.identifier.citation | Makgai, L.M. 2022. Efavirenz pharmacogenetics and metabolic toxicity in black South Africans. . ,Faculty of Health Sciences ,Department of Medicine. http://hdl.handle.net/11427/37486 | en_ZA |
| dc.identifier.ris | TY - Master Thesis AU - Makgai, Lesiba Meshack AB - 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. DA - 2022_ DB - OpenUCT DP - University of Cape Town KW - Clinical Pharmacology LK - https://open.uct.ac.za PY - 2022 T1 - Efavirenz pharmacogenetics and metabolic toxicity in black South Africans TI - Efavirenz pharmacogenetics and metabolic toxicity in black South Africans UR - http://hdl.handle.net/11427/37486 ER - | en_ZA |
| dc.identifier.uri | http://hdl.handle.net/11427/37486 | |
| dc.identifier.vancouvercitation | Makgai LM. Efavirenz pharmacogenetics and metabolic toxicity in black South Africans. []. ,Faculty of Health Sciences ,Department of Medicine, 2022 [cited yyyy month dd]. Available from: http://hdl.handle.net/11427/37486 | en_ZA |
| dc.language.rfc3066 | eng | |
| dc.publisher.department | Department of Medicine | |
| dc.publisher.faculty | Faculty of Health Sciences | |
| dc.subject | Clinical Pharmacology | |
| dc.title | Efavirenz pharmacogenetics and metabolic toxicity in black South Africans | |
| dc.type | Master Thesis | |
| dc.type.qualificationlevel | Masters | |
| dc.type.qualificationlevel | MPhil |