Document Detail


Mitochondrial toxicity in HIV type-1-exposed pregnancies in the era of highly active antiretroviral therapy.
MedLine Citation:
PMID:  19474467     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: The aim of this study was to determine the effects of HIV type-1 (HIV-1) infection and antiretroviral therapy (ART) on placental mitochondria. METHODS: HIV-1-infected pregnant women and HIV-1-uninfected controls were enrolled prospectively. Placental mitochondrial DNA (mtDNA) copy numbers were determined by quantitative PCR, subunits II and IV of cytochrome c oxidase (COX) were quantified by western blot and mitochondrial ultrastructure was evaluated by electron microscopy. Venous blood lactate was measured in newborns. RESULTS: In total, 45 HIV-1-infected pregnant women on ART and 32 controls were included. Mean +/-sd mtDNA copy numbers were significantly reduced in ART and HIV-1-exposed placentas (240 +/-118 copies/cell) in comparison with controls (686 +/-842 copies/cell; P<0.001). The mean COX II/IV ratio was 48% lower in the investigational group compared with controls (P<0.001). There was no evidence of severe ultrastructural damage within mitochondria of HIV-1-infected ART-exposed placentas. Although lactate levels between newborns did not differ, they were negatively correlated with placental mtDNA levels. There was no clear association between mitochondrial parameters and a particular nucleoside reverse transcriptase inhibitor (NRTI), the number of NRTIs or time of NRTI exposure. CONCLUSIONS: Placental tissue of HIV-1-infected ART-exposed pregnancies shows evidence of mtDNA depletion with secondary respiratory chain compromise. The clinical effects of this finding warrant further investigation.
Authors:
Andrea Gingelmaier; Thomas A Grubert; Bernd P Kost; Bernhard Setzer; Dirk Lebrecht; Ioannis Mylonas; Josef Mueller-Hoecker; Udo Jeschke; Stephan Hiedl; Klaus Friese; Ulrich A Walker
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Antiviral therapy     Volume:  14     ISSN:  1359-6535     ISO Abbreviation:  Antivir. Ther. (Lond.)     Publication Date:  2009  
Date Detail:
Created Date:  2009-05-28     Completed Date:  2009-07-30     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9815705     Medline TA:  Antivir Ther     Country:  England    
Other Details:
Languages:  eng     Pagination:  331-8     Citation Subset:  IM    
Affiliation:
Department of Obstetrics and Gynaecology, Ludwig Maximilians University of Munich, Munich, Germany. andrea.gingelmaier@med.uni-muenchen.de
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MeSH Terms
Descriptor/Qualifier:
Adult
Anti-HIV Agents / adverse effects*,  therapeutic use
Antiretroviral Therapy, Highly Active / adverse effects
DNA, Mitochondrial / analysis
Electron Transport Complex IV / metabolism
Female
HIV Infections / drug therapy*
HIV-1*
Humans
Infant, Newborn / blood
Lactic Acid / blood
Mitochondria / drug effects*,  metabolism,  ultrastructure
Placenta / drug effects*,  metabolism,  ultrastructure
Pregnancy
Pregnancy Complications, Infectious / drug therapy,  virology*
Retrospective Studies
Chemical
Reg. No./Substance:
0/Anti-HIV Agents; 0/DNA, Mitochondrial; 50-21-5/Lactic Acid; EC 1.9.3.-/cytochrome C oxidase subunit II; EC 1.9.3.1/Electron Transport Complex IV

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