Whole Blood Mitochondrial DNA Depletion in Human Immunodeficiency Virus-Infected Children

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dc.contributor.advisorHenderson, Howarden_ZA
dc.contributor.advisorEley, Brianen_ZA
dc.contributor.authorvan der Watt, George Fredericken_ZA
dc.date.accessioned2014-07-28T08:15:52Z
dc.date.available2014-07-28T08:15:52Z
dc.date.issued2010en_ZA
dc.description.abstractBackground: Nucleoside reverse transcriptase inhibitors (NRTIs) interfere with mitochondrial DNA polymerase gamma causing significant toxic effects, including fatal lactic acidosis. Little is known about mitochondrial DNA (mtDNA) in human immunodeficiency virus (HIV) infected children who face a lifetime exposure to these agents. We performed a cross sectional observation of mtDNA levels in whole blood in a pediatric population to ascertain the relationship between mtDNA, NRTI regimens and parameters of HIV-infection severity. Methods: Whole blood mt:nDNA ratios were determined by real-time PCR in three groups: 27 presumed HIV-negative, 89 HIV-infected, NRTI-treated and 62 HIV-infected treatment-naive children. Multivariate analysis was used to identify variables independently associated with mtDNA depletion. Results: Mean mt:nDNA ratios were lower (P < 0.001) at 77% of control in the HIVinfected antiretroviral treatment (ART) Naïve group and 73% of control in the ART group, but not different between the two HIV-infected groups. Mt:nDNA ratios were negatively associated with age (P = 0.029), HIV status (P < 0.0001) and Log10 of the HIV-1 viral load (P = 0.035) and positively associated with CD4 % (p = 0.032). A 6 stavudine vs zidovudine based regimen was associated with lower but not significant levels of mtDNA (P = 0.1). Conclusions: Depletion of whole blood mtDNA in children is associated independently with HIV-infection and markers of HIV infection severity, and does not improve with either stavudine or zidovudine based ART despite virological control, suggesting that these agents also deplete mtDNA.en_ZA
dc.identifier.apacitationvan der Watt, G. F. (2010). <i>Whole Blood Mitochondrial DNA Depletion in Human Immunodeficiency Virus-Infected Children</i>. (Thesis). University of Cape Town ,Faculty of Health Sciences ,Division of Chemical Pathology. Retrieved from http://hdl.handle.net/11427/2705en_ZA
dc.identifier.chicagocitationvan der Watt, George Frederick. <i>"Whole Blood Mitochondrial DNA Depletion in Human Immunodeficiency Virus-Infected Children."</i> Thesis., University of Cape Town ,Faculty of Health Sciences ,Division of Chemical Pathology, 2010. http://hdl.handle.net/11427/2705en_ZA
dc.identifier.citationvan der Watt, G. 2010. Whole Blood Mitochondrial DNA Depletion in Human Immunodeficiency Virus-Infected Children. University of Cape Town.en_ZA
dc.identifier.ris TY - Thesis / Dissertation AU - van der Watt, George Frederick AB - Background: Nucleoside reverse transcriptase inhibitors (NRTIs) interfere with mitochondrial DNA polymerase gamma causing significant toxic effects, including fatal lactic acidosis. Little is known about mitochondrial DNA (mtDNA) in human immunodeficiency virus (HIV) infected children who face a lifetime exposure to these agents. We performed a cross sectional observation of mtDNA levels in whole blood in a pediatric population to ascertain the relationship between mtDNA, NRTI regimens and parameters of HIV-infection severity. Methods: Whole blood mt:nDNA ratios were determined by real-time PCR in three groups: 27 presumed HIV-negative, 89 HIV-infected, NRTI-treated and 62 HIV-infected treatment-naive children. Multivariate analysis was used to identify variables independently associated with mtDNA depletion. Results: Mean mt:nDNA ratios were lower (P < 0.001) at 77% of control in the HIVinfected antiretroviral treatment (ART) Naïve group and 73% of control in the ART group, but not different between the two HIV-infected groups. Mt:nDNA ratios were negatively associated with age (P = 0.029), HIV status (P < 0.0001) and Log10 of the HIV-1 viral load (P = 0.035) and positively associated with CD4 % (p = 0.032). A 6 stavudine vs zidovudine based regimen was associated with lower but not significant levels of mtDNA (P = 0.1). Conclusions: Depletion of whole blood mtDNA in children is associated independently with HIV-infection and markers of HIV infection severity, and does not improve with either stavudine or zidovudine based ART despite virological control, suggesting that these agents also deplete mtDNA. DA - 2010 DB - OpenUCT DP - University of Cape Town LK - https://open.uct.ac.za PB - University of Cape Town PY - 2010 T1 - Whole Blood Mitochondrial DNA Depletion in Human Immunodeficiency Virus-Infected Children TI - Whole Blood Mitochondrial DNA Depletion in Human Immunodeficiency Virus-Infected Children UR - http://hdl.handle.net/11427/2705 ER - en_ZA
dc.identifier.urihttp://hdl.handle.net/11427/2705
dc.identifier.vancouvercitationvan der Watt GF. Whole Blood Mitochondrial DNA Depletion in Human Immunodeficiency Virus-Infected Children. [Thesis]. University of Cape Town ,Faculty of Health Sciences ,Division of Chemical Pathology, 2010 [cited yyyy month dd]. Available from: http://hdl.handle.net/11427/2705en_ZA
dc.language.isoeng
dc.publisher.departmentDivision of Chemical Pathologyen_ZA
dc.publisher.facultyFaculty of Health Sciencesen_ZA
dc.publisher.institutionUniversity of Cape Town
dc.subject.otherChemical Pathologyen_ZA
dc.titleWhole Blood Mitochondrial DNA Depletion in Human Immunodeficiency Virus-Infected Childrenen_ZA
dc.typeMaster Thesis
dc.type.qualificationlevelMasters
uct.type.filetypeText
uct.type.filetypeImage
uct.type.publicationResearchen_ZA
uct.type.resourceThesisen_ZA
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