Document Detail


Mitochondrial damage and DNA depletion in cord blood and umbilical cord from infants exposed in utero to Combivir.
MedLine Citation:
PMID:  15096804     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Rao L Divi; Vernon E Walker; Nancy A Wade; Kunio Nagashima; Steven K Seilkop; Mary Ellen Adams; Carol J Nesel; J Patrick O'Neill; Elaine J Abrams; Miriam C Poirier
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Publication Detail:
Type:  Journal Article; Multicenter Study; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  AIDS (London, England)     Volume:  18     ISSN:  0269-9370     ISO Abbreviation:  AIDS     Publication Date:  2004 Apr 
Date Detail:
Created Date:  2004-04-20     Completed Date:  2004-08-03     Revised Date:  2009-10-02    
Medline Journal Info:
Nlm Unique ID:  8710219     Medline TA:  AIDS     Country:  England    
Other Details:
Languages:  eng     Pagination:  1013-21     Citation Subset:  IM; X    
Affiliation:
CDI Section, National Cancer Institute, NIH, Bethesda, Maryland 20892, USA.
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MeSH Terms
Descriptor/Qualifier:
Anti-HIV Agents / adverse effects*
CD4 Lymphocyte Count
DNA, Mitochondrial / analysis*,  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*,  ultrastructure
Pilot Projects
Pregnancy
Pregnancy Complications, Infectious / drug therapy
Prenatal Exposure Delayed Effects
Umbilical Cord / metabolism,  ultrastructure
Zidovudine / adverse effects*
Grant Support
ID/Acronym/Agency:
R01-HD33648/HD/NICHD NIH HHS; R01-HL72727/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Anti-HIV Agents; 0/DNA, Mitochondrial; 0/Drug Combinations; 0/lamivudine, zidovudine drug combination; 134678-17-4/Lamivudine; 30516-87-1/Zidovudine

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