title: Increased mtDNA levels without change in mitochondrial enzymes in peripheral blood mononuclear cells of infants born to HIV-infected mothers on antiretroviral therapy.
abstract: BACKGROUND
  The effects of gestational nucleoside reverse transcriptase inhibitors (NRTIs) on mitochondrial DNA (mtDNA) are controversial. The effects of mtDNA depletion on mitochondrial function have not been assessed.
  
  
  METHODS
  In peripheral blood mononuclear cells (PBMCs) from infants born to HIV-infected women and infants born to HIV-1-uninfected women, mtDNA copy numbers were determined by quantitative PCR; nuclear (COXIV)- and mitochondrial (COXII)-encoded polypeptides of the oxidative phosphorylation enzyme cytochrome c-oxidase (COX or complex IV) were quantified by Western blot.
  
  
  RESULTS
  Overall, 86 infants born to HIV-infected women and 50 controls were studied. HIV-infected mothers had a median CD4 count of 506 cells/microL; 59% had HIV RNA 50 copies/mL. No infant had clinical evidence of mitochondrial disease. The birth weight was lower (p = .016) and the body length higher (p = .002) in the HIV-exposed newborns. Eighty-one HIV-infected women had received gestational NRTIs (median duration 162 days). Median mtDNA copies/PBMC in the HIV-exposed infants were 505 (range, 120-1365) vs. 213 (27-426) in controls (p < .001). COX II/IV ratios were similar in both groups. Although mtDNA levels correlated inversely with maternal lactate, mitochondrial indices did not correlate with maternal CD4+ count, HIV RNA, smoking, or alcohol consumption.
  
  
  CONCLUSIONS
  We found elevated mtDNA copy numbers in PBMC of infants born to HIV-infected women, the majority of whom received NRTI-based therapy, when compared to those born to healthy HIV-negative controls, but there was no difference in mtDNA-encoded respiratory chain protein. The clinical consequence of these findings is unknown and requires further investigations.
authors.affiliation: Case Western Reserve University, Cleveland, Ohio 44106, USA. mccomsey.grace@clevelandactu.org
authors.forename: Grace A
authors.initials: GA
authors.lastname: McComsey
authors.forename: Minhee
authors.initials: M
authors.lastname: Kang
authors.forename: Allison C
authors.initials: AC
authors.lastname: Ross
authors.forename: Dirk
authors.initials: D
authors.lastname: Lebrecht
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Livingston
authors.forename: Ann
authors.initials: A
authors.lastname: Melvin
authors.forename: Jane
authors.initials: J
authors.lastname: Hitti
authors.forename: Susan E
authors.initials: SE
authors.lastname: Cohn
authors.forename: Ulrich A
authors.initials: UA
authors.lastname: Walker
mesh_terms: D000293:Adolescent; D000328:Adult; D001724:Birth Weight; D015153:Blotting, Western; D001827:Body Height; D018791:CD4 Lymphocyte Count; D045304:Cytochromes c / Q000032:analysis; D004272:DNA, Mitochondrial / Q000032:analysis*; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D015497:HIV-1 / Q000302:isolation & purification; D006801:Humans; D007231:Infant, Newborn; D007963:Leukocytes, Mononuclear / Q000737:chemistry* / Q000201:enzymology*; D024101:Mitochondrial Proteins / Q000032:analysis*; D016133:Polymerase Chain Reaction / Q000379:methods; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000188:drug therapy; D012367:RNA, Viral / Q000097:blood; D019562:Viral Load
chemical_list: D004272:DNA, Mitochondrial; D024101:Mitochondrial Proteins; D012367:RNA, Viral; D045304:Cytochromes c