Mitochondrial damage and DNA depletion in cord blood and umbilical cord from infants exposed in utero to Combivir.
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.
Divi
Rao L
RL
CDI Section, National Cancer Institute, NIH, Bethesda, Maryland 20892, USA.
Walker
Vernon E
VE
Wade
Nancy A
NA
Nagashima
Kunio
K
Seilkop
Steven K
SK
Adams
Mary Ellen
ME
Nesel
Carol J
CJ
O'Neill
J Patrick
JP
Abrams
Elaine J
EJ
Poirier
Miriam C
MC
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*
D019380:Anti-HIV Agents; D004272:DNA, Mitochondrial; D004338:Drug Combinations; C109078:lamivudine, zidovudine drug combination; D019259:Lamivudine; D015215:Zidovudine