Mitochondrial damage and DNA depletion in cord blood and umbilical cord from infants exposed in utero to Combivir

AIDS. 2004 Apr 30;18(7):1013-21. doi: 10.1097/00002030-200404300-00009.

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.

Design: : 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.

Publication types

  • Multicenter Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Anti-HIV Agents / adverse effects*
  • CD4 Lymphocyte Count
  • DNA, Mitochondrial / analysis*
  • DNA, Mitochondrial / drug effects
  • Drug Combinations
  • Female
  • Fetal Blood / metabolism
  • HIV Infections / drug therapy
  • HIV-1 / isolation & purification
  • Humans
  • Infant, Newborn
  • Lamivudine / adverse effects*
  • Maternal-Fetal Exchange*
  • Microscopy, Electron
  • Mitochondria / drug effects*
  • Mitochondria / ultrastructure
  • Pilot Projects
  • Pregnancy
  • Pregnancy Complications, Infectious / drug therapy
  • Prenatal Exposure Delayed Effects
  • Umbilical Cord / metabolism
  • Umbilical Cord / ultrastructure
  • Zidovudine / adverse effects*

Substances

  • Anti-HIV Agents
  • DNA, Mitochondrial
  • Drug Combinations
  • lamivudine, zidovudine drug combination
  • Lamivudine
  • Zidovudine