title: Effects of in utero antiretroviral exposure on mitochondrial DNA levels, mitochondrial function and oxidative stress.
abstract: OBJECTIVE
  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.
authors: Emory University School of Medicine, Atlanta, GA, USA. across3@emory.edu
authors: A C
authors: AC
authors: Ross
authors: T
authors: T
authors: Leong
authors: A
authors: A
authors: Avery
authors: M
authors: M
authors: Castillo-Duran
authors: H
authors: H
authors: Bonilla
authors: D
authors: D
authors: Lebrecht
authors: U A
authors: UA
authors: Walker
authors: N
authors: N
authors: Storer
authors: D
authors: D
authors: Labbato
authors: A
authors: A
authors: Khaitan
authors: I
authors: I
authors: Tomanova-Soltys
authors: G A
authors: GA
authors: McComsey
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000009:adverse effects*; D016022:Case-Control Studies; D004272:DNA, Mitochondrial / Q000187:drug effects* / Q000235:genetics; D003576:Electron Transport Complex IV / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005312:Fetal Blood / Q000187:drug effects / Q000201:enzymology*; D015658:HIV Infections / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D007231:Infant, Newborn; D008431:Maternal-Fetal Exchange; D018384:Oxidative Stress / Q000187:drug effects* / Q000235:genetics; D010920:Placenta / Q000187:drug effects / Q000201:enzymology*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D011446:Prospective Studies; D055815:Young Adult
chemical_list: D019380:Anti-HIV Agents; D004272:DNA, Mitochondrial; C117108:cytochrome C oxidase subunit II; D003576:Electron Transport Complex IV