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

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 g...

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Main Author: Sinxadi, Phumla Z
Other Authors: Maartens, Gary
Format: Thesis
Language:English
Published: Division of Clinical Pharmacology 2016
Subjects:
Clinical Pharmacology
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access_status_str Open Access
author Sinxadi, Phumla Z
author2 Maartens, Gary
author_browse Maartens, Gary
Sinxadi, Phumla Z
author_facet Maartens, Gary
Sinxadi, Phumla Z
author_sort Sinxadi, Phumla Z
collection Thesis
description 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.
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institution University of Cape Town (South Africa)
language eng
last_indexed 2026-06-10T12:34:20.437Z
license_str Not specified — see source repository
provenance_str_mv Harvested via OAI-PMH from UCTD — University of Cape Town Open Access Repository
publishDate 2016
publishDateRange 2016
publishDateSort 2016
publisher Division of Clinical Pharmacology
publisherStr Division of Clinical Pharmacology
record_format dspace
source_str UCTD — University of Cape Town Open Access Repository
spelling oai:open.uct.ac.za:11427/20329 Pharmacogenomics and pharmacokinetics of antiretroviral drugs and their associations with metabolic complications in HIV-infected Black South Africans Sinxadi, Phumla Z Maartens, Gary Haas, David W Clinical Pharmacology 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. 2016-07-13T07:46:57Z 2016-07-13T07:46:57Z 2016 Doctoral Thesis Doctoral PhD http://hdl.handle.net/11427/20329 eng application/pdf Division of Clinical Pharmacology Faculty of Health Sciences University of Cape Town
spellingShingle Clinical Pharmacology
Sinxadi, Phumla Z
Pharmacogenomics and pharmacokinetics of antiretroviral drugs and their associations with metabolic complications in HIV-infected Black South Africans
thesis_degree_str Doctoral
title Pharmacogenomics and pharmacokinetics of antiretroviral drugs and their associations with metabolic complications in HIV-infected Black South Africans
title_full Pharmacogenomics and pharmacokinetics of antiretroviral drugs and their associations with metabolic complications in HIV-infected Black South Africans
title_fullStr Pharmacogenomics and pharmacokinetics of antiretroviral drugs and their associations with metabolic complications in HIV-infected Black South Africans
title_full_unstemmed Pharmacogenomics and pharmacokinetics of antiretroviral drugs and their associations with metabolic complications in HIV-infected Black South Africans
title_short Pharmacogenomics and pharmacokinetics of antiretroviral drugs and their associations with metabolic complications in HIV-infected Black South Africans
title_sort pharmacogenomics and pharmacokinetics of antiretroviral drugs and their associations with metabolic complications in hiv infected black south africans
topic Clinical Pharmacology
url http://hdl.handle.net/11427/20329
work_keys_str_mv AT sinxadiphumlaz pharmacogenomicsandpharmacokineticsofantiretroviraldrugsandtheirassociationswithmetaboliccomplicationsinhivinfectedblacksouthafricans

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