title: Mitochondrial damage and DNA depletion in cord blood and umbilical cord from infants exposed in utero to Combivir.
abstract: OBJECTIVE
  Although most uninfected infants born to women infected with HIV-1 show no clinical evidence of mitochondrial compromise, mitochondrial dysfunction has been reported in children born to women receiving zidovudine and/or lamivudine during pregnancy. In this pilot study we examined mitochondrial integrity in HIV-1-uninfected infants born to HIV-1-infected women receiving Combivir during pregnancy.
  
  
  METHODS
  : Samples of umbilical cord and cord blood were obtained from HIV-1-uninfected infants born to either HIV-1-infected women receiving Combivir therapy during pregnancy (n = 10) or HIV-1-uninfected women (n = 9).
  
  
  METHODS
  Mitochondrial morphological integrity was examined in umbilical cords (n = 16) by electron microscopy and mtDNA quantity was determined in DNA from cord blood (n = 18) and umbilical cord (n = 18) by PCR-chemiluminescence immunoassay detection.
  
  
  RESULTS
  In umbilical cords from six of nine infants born to HIV-1-infected mothers taking Combivir moderate to severe mitochondrial morphological damage was observed (P = 0.011), while none of seven unexposed infants showed similar damage. Compared to unexposed infants, statistically significant mtDNA depletion was observed in umbilical cord (P = 0.006) and cord blood (P = 0.003) from drug-exposed infants.
  
  
  CONCLUSIONS
  A cohort of HIV-1-uninfected Combivir-exposed infants with no clinical symptoms showed morphological and molecular evidence of mitochondrial damage.
authors.affiliation: CDI Section, National Cancer Institute, NIH, Bethesda, Maryland 20892, USA.
authors.forename: Rao L
authors.initials: RL
authors.lastname: Divi
authors.forename: Vernon E
authors.initials: VE
authors.lastname: Walker
authors.forename: Nancy A
authors.initials: NA
authors.lastname: Wade
authors.forename: Kunio
authors.initials: K
authors.lastname: Nagashima
authors.forename: Steven K
authors.initials: SK
authors.lastname: Seilkop
authors.forename: Mary Ellen
authors.initials: ME
authors.lastname: Adams
authors.forename: Carol J
authors.initials: CJ
authors.lastname: Nesel
authors.forename: J Patrick
authors.initials: JP
authors.lastname: O'Neill
authors.forename: Elaine J
authors.initials: EJ
authors.lastname: Abrams
authors.forename: Miriam C
authors.initials: MC
authors.lastname: Poirier
mesh_terms: D019380:Anti-HIV Agents / Q000009:adverse effects*; D018791:CD4 Lymphocyte Count; D004272:DNA, Mitochondrial / Q000032:analysis* / Q000187:drug effects; D004338:Drug Combinations; D005260:Female; D005312:Fetal Blood / Q000378:metabolism; D015658:HIV Infections / Q000188:drug therapy; D015497:HIV-1 / Q000302:isolation & purification; D006801:Humans; D007231:Infant, Newborn; D019259:Lamivudine / Q000009:adverse effects*; D008431:Maternal-Fetal Exchange; D008854:Microscopy, Electron; D008928:Mitochondria / Q000187:drug effects* / Q000648:ultrastructure; D010865:Pilot Projects; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000188:drug therapy; D011297:Prenatal Exposure Delayed Effects; D014470:Umbilical Cord / Q000378:metabolism / Q000648:ultrastructure; D015215:Zidovudine / Q000009:adverse effects*
chemical_list: D019380:Anti-HIV Agents; D004272:DNA, Mitochondrial; D004338:Drug Combinations; C109078:lamivudine, zidovudine drug combination; D019259:Lamivudine; D015215:Zidovudine