Pharmacogenomics and pharmacokinetics of antiretroviral drugs and their associations with metabolic complications in HIV-infected Black South Africans

 

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dc.contributor.advisor Maartens, Gary en_ZA
dc.contributor.advisor Haas, David W en_ZA
dc.contributor.author Sinxadi, Phumla Z en_ZA
dc.date.accessioned 2016-07-13T07:46:57Z
dc.date.available 2016-07-13T07:46:57Z
dc.date.issued 2016 en_ZA
dc.identifier.citation Sinxadi, P. 2016. Pharmacogenomics and pharmacokinetics of antiretroviral drugs and their associations with metabolic complications in HIV-infected Black South Africans. University of Cape Town. en_ZA
dc.identifier.uri http://hdl.handle.net/11427/20329
dc.description.abstract BACKGROUND: Antiretroviral therapy (ART), notably efavirenz and lopinavir, have been associated with metabolic abnormalities known to increase cardiovascular risk. Efavirenz and lopinavir pharmacokinetics demonstrate considerable interindividual variability, which in part, may be explained by host genetic factors. Mitochondrial DNA (mtDNA) variation influences ART related metabolic complications. However, the associations between genetic polymorphisms and pharmacokinetics of antiretroviral drugs, and their associations with metabolic complications, are incompletely understood. We explored associations of mitochondrial DNA (mtDNA) haplogroups and ART related metabolic complications, characterized relationships between genetic polymorphisms and plasma efavirenz concentrations, and investigated associations between plasma efavirenz/lopinavir concentrations and lipid and glucose concentrations in HIVinfected Black South Africans. METHODS: We collected clinical and laboratory data from HIV infected patients on ART from Cape Town. We sequenced the mitochondrial genome and determined African mtDNA haplogroups. We genotyped 241 polymorphisms in genes potentially relevant to efavirenz metabolism and transport. We measured steady state efavirenz and lopinavir concentrations and used regression analyses to determine associations with metabolic parameters. en_ZA
dc.language.iso eng en_ZA
dc.subject.other Clinical Pharmacology en_ZA
dc.title Pharmacogenomics and pharmacokinetics of antiretroviral drugs and their associations with metabolic complications in HIV-infected Black South Africans en_ZA
dc.type Doctoral Thesis
uct.type.publication Research en_ZA
uct.type.resource Thesis en_ZA
dc.publisher.institution University of Cape Town
dc.publisher.faculty Faculty of Health Sciences en_ZA
dc.publisher.department Division of Clinical Pharmacology en_ZA
dc.type.qualificationlevel Doctoral
dc.type.qualificationname PhD en_ZA
uct.type.filetype Text
uct.type.filetype Image
dc.identifier.apacitation Sinxadi, P. Z. (2016). <i>Pharmacogenomics and pharmacokinetics of antiretroviral drugs and their associations with metabolic complications in HIV-infected Black South Africans</i>. (Thesis). University of Cape Town ,Faculty of Health Sciences ,Division of Clinical Pharmacology. Retrieved from http://hdl.handle.net/11427/20329 en_ZA
dc.identifier.chicagocitation Sinxadi, Phumla Z. <i>"Pharmacogenomics and pharmacokinetics of antiretroviral drugs and their associations with metabolic complications in HIV-infected Black South Africans."</i> Thesis., University of Cape Town ,Faculty of Health Sciences ,Division of Clinical Pharmacology, 2016. http://hdl.handle.net/11427/20329 en_ZA
dc.identifier.vancouvercitation Sinxadi PZ. Pharmacogenomics and pharmacokinetics of antiretroviral drugs and their associations with metabolic complications in HIV-infected Black South Africans. [Thesis]. University of Cape Town ,Faculty of Health Sciences ,Division of Clinical Pharmacology, 2016 [cited yyyy month dd]. Available from: http://hdl.handle.net/11427/20329 en_ZA
dc.identifier.ris TY - Thesis / Dissertation AU - Sinxadi, Phumla Z AB - BACKGROUND: Antiretroviral therapy (ART), notably efavirenz and lopinavir, have been associated with metabolic abnormalities known to increase cardiovascular risk. Efavirenz and lopinavir pharmacokinetics demonstrate considerable interindividual variability, which in part, may be explained by host genetic factors. Mitochondrial DNA (mtDNA) variation influences ART related metabolic complications. However, the associations between genetic polymorphisms and pharmacokinetics of antiretroviral drugs, and their associations with metabolic complications, are incompletely understood. We explored associations of mitochondrial DNA (mtDNA) haplogroups and ART related metabolic complications, characterized relationships between genetic polymorphisms and plasma efavirenz concentrations, and investigated associations between plasma efavirenz/lopinavir concentrations and lipid and glucose concentrations in HIVinfected Black South Africans. METHODS: We collected clinical and laboratory data from HIV infected patients on ART from Cape Town. We sequenced the mitochondrial genome and determined African mtDNA haplogroups. We genotyped 241 polymorphisms in genes potentially relevant to efavirenz metabolism and transport. We measured steady state efavirenz and lopinavir concentrations and used regression analyses to determine associations with metabolic parameters. DA - 2016 DB - OpenUCT DP - University of Cape Town LK - https://open.uct.ac.za PB - University of Cape Town PY - 2016 T1 - Pharmacogenomics and pharmacokinetics of antiretroviral drugs and their associations with metabolic complications in HIV-infected Black South Africans TI - Pharmacogenomics and pharmacokinetics of antiretroviral drugs and their associations with metabolic complications in HIV-infected Black South Africans UR - http://hdl.handle.net/11427/20329 ER - en_ZA


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