Effects of in utero antiretroviral exposure onmitochondrial DNA levels, mitochondrial function and oxidativestress

• Type of Material: Article
• Authors: Allison Ross Eckard, Emory University; Traci Leong, Emory University; A Avery, Case Western Reserve University; M Castillo-Duran, MetroHealth Medical Center; H Bonilla, Summa Health System; D Lebrecht, Medizinische Universitätsklinik; UA Walker, Medizinische Universitätsklinik; N Storer, Case Western Reserve University; D Labbato, Case Western Reserve University; A Khaitan, Case Western Reserve University; I Tomanova-Soltys, Case Western Reserve University; GA McComsey, Case Western Reserve University
• Language: English
• Date: 2012-02
• Publisher: Wiley: 12 months
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2011 British HIV Association
• Final Published Version (URL): http://onlinelibrary.wiley.com/doi/10.1111/j.1468-1293.2011.00945.x/abstract?systemMessage=Wiley+Online+Library+will+be+disrupted+Saturday%2C+15+March+from+10%3A00-12%3A00+GMT+%2806%3A00-08%3A00+EDT%29+for+essential+maintenance
• Title of Journal or Parent Work: HIV Medicine
• ISSN: 1464-2662
• Volume: 13
• Issue: 2
• Start Page: 98
• End Page: 106
• Grant/Funding Information: The study was supported by NIH grant R01 AI065348-01 (to GAM) and the Clinical Core of the Case Center for AIDS Research (NIH grant AI36219).
• Keywords: mitochondrial DNA; antiretroviral agents; vertical transmission; HIV infection; infants; toxicity
• Research Categories: Health Sciences, General

Abstract

Objectives HIV and antiretroviral (ART) exposure in utero may have deleterious effects on the infant, but uncertainty still exists. The objective of this study was to evaluate aspects of mitochondrial DNA (mtDNA) content, mitochondrial function and oxidative stress simultaneously in placenta, umbilical cord blood and infant blood in HIV/ART-exposed infants compared with uninfected controls. Methods HIV-1-infected pregnant women and HIV-1-uninfected healthy pregnant controls were enrolled in the study prospectively. Placenta and umbilical cord blood were obtained at delivery and infant blood was obtained within 48 h of delivery. mtDNA content was determined for each specimen. Nuclear [subunit IV of cytochrome c-oxidase (COX IV)]- and mitochondrial (COX II)-encoded polypeptides of the oxidative phosphorylation enzyme cytochrome c-oxidase were quantified in cord and infant blood. Placental mitochondria malondialdehyde (MDA) concentrations were measured as a marker of oxidative stress. Results Twenty HIV-positive/HIV-exposed and 26 control mother–infant pairs were enrolled in the study. All HIV-infected women and their infants received ART. Placental MDA concentration and mtDNA content in placenta and cord blood were similar between groups. The cord blood COX II:IV ratio was lower in the HIV-positive group than in the controls, whereas the infant peripheral blood mtDNA content was higher in the HIV-exposed infants, but the infant peripheral blood COX II:IV ratio was similar. No infant had clinical evidence of mitochondrial disease or acquired HIV infection. In multivariable regression analyses, the significant findings in cord and infant blood were both most associated with HIV/ART exposure. Conclusions HIV-exposed infants showed reduced umbilical cord blood mitochondrial enzyme expression with increased infant peripheral blood mitochondrial DNA levels, the latter possibly reflecting a compensatory mechanism to overcome HIV/ART-associated mitochondrial toxicity.