| Mitochondrial toxicity in HIV type-1-exposed pregnancies in the era of highly active antiretroviral therapy. | |
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MedLine Citation:
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PMID: 19474467 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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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:
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Type: Journal Article |
Journal Detail:
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Title: Antiviral therapy Volume: 14 ISSN: 1359-6535 ISO Abbreviation: Antivir. Ther. (Lond.) Publication Date: 2009 |
Date Detail:
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Created Date: 2009-05-28 Completed Date: 2009-07-30 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9815705 Medline TA: Antivir Ther Country: England |
Other Details:
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Languages: eng Pagination: 331-8 Citation Subset: IM |
Affiliation:
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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:
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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:
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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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