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

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dc.contributor.advisorMaartens, Garyen_ZA
dc.contributor.advisorHaas, David Wen_ZA
dc.contributor.authorSinxadi, Phumla Zen_ZA
dc.date.accessioned2016-07-13T07:46:57Z
dc.date.available2016-07-13T07:46:57Z
dc.date.issued2016en_ZA
dc.description.abstractBACKGROUND: 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.identifier.apacitationSinxadi, 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/11427/20329en_ZA
dc.identifier.chicagocitationSinxadi, 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/11427/20329en_ZA
dc.identifier.citationSinxadi, 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.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
dc.identifier.urihttp://hdl.handle.net/11427/20329
dc.identifier.vancouvercitationSinxadi 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/11427/20329en_ZA
dc.language.isoengen_ZA
dc.publisher.departmentDivision of Clinical Pharmacologyen_ZA
dc.publisher.facultyFaculty of Health Sciencesen_ZA
dc.publisher.institutionUniversity of Cape Town
dc.subject.otherClinical Pharmacologyen_ZA
dc.titlePharmacogenomics and pharmacokinetics of antiretroviral drugs and their associations with metabolic complications in HIV-infected Black South Africansen_ZA
dc.typeDoctoral Thesis
dc.type.qualificationlevelDoctoral
dc.type.qualificationnamePhDen_ZA
uct.type.filetypeText
uct.type.filetypeImage
uct.type.publicationResearchen_ZA
uct.type.resourceThesisen_ZA
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