title: Fetal consequences of maternal antiretroviral nucleoside reverse transcriptase inhibitor use in human and nonhuman primate pregnancy.
abstract: OBJECTIVE
  Here we present fetal genotoxicity and mitochondrial toxicity, induced by nucleoside reverse transcriptase inhibitors (NRTIs), in HIV-1-infected pregnant women treated to prevent mother-to-child HIV-1 transmission, and in virus-free pregnant patas monkeys.
  
  
  RESULTS
  In the offspring of pregnant patas monkeys given human-equivalent NRTI protocols, aneuploidy was found in cultured bone marrow cells taken at birth, 1, and 3 years of age. In some newborn human infants, the offspring of HIV-1-infected mothers given zidovudine (AZT) therapy, aneuploidy, mitochondrial DNA (mtDNA) depletion, morphologically damaged mitochondria, and reduction in cardiac left ventricular muscle were observed. NRTI-exposed human and patas umbilical cords had similar levels of mtDNA depletion and mitochondrial morphological damage. NRTI-exposed patas offspring showed a compensatory increase in heart mtDNA, and a 50% loss of brain mtDNA at 1 year of age. Mitochondrial morphological damage and mtDNA loss were persistent in blood cells of NRTI-exposed infants up to 2 years of age, and in heart and brain from NRTI-exposed patas up to 3 years of age (human equivalent of 15 years).
  
  
  CONCLUSIONS
  Whereas use of NRTIs in human pregnancy protects many thousands of children worldwide, some HIV-1-uninfected infants born to HIV-1-infected mothers receiving antiretroviral drug therapy sustain toxicities that may have adverse consequences later in life.
authors: aCarcinogen-DNA Interactions Section, Laboratory of Cancer Biology and Genetics, CCR, National Cancer Institute, NIH, Bethesda, Maryland, USA bGrupo Imunovirologia, School of Medicine Universidad de Antioquia, Medellin, Colombia cInstitut National de la Sante et de la Recherche Medicale, Universite Paris Descartes, Sorbonne Paris Cite, Paris, France dUnite d'Immunologie-Hematologie Pediatrique, Hopital Necker-Enfants Malades, Paris, France.
authors: Miriam C
authors: MC
authors: Poirier
authors: Alexander T
authors: AT
authors: Gibbons
authors: Maria T
authors: MT
authors: Rugeles
authors: Isabelle
authors: I
authors: Andre-Schmutz
authors: Stephane
authors: S
authors: Blanche
mesh_terms: D000782:Aneuploidy; D000818:Animals; D000831:Animals, Newborn; D004272:DNA, Mitochondrial / Q000187:drug effects* / Q000502:physiology; D004195:Disease Models, Animal; D004901:Erythrocebus patas; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000517:prevention & control; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D018445:Infectious Disease Transmission, Vertical / Q000517:prevention & control*; D008431:Maternal-Fetal Exchange; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000188:drug therapy*; D018894:Reverse Transcriptase Inhibitors / Q000009:adverse effects* / Q000494:pharmacology / Q000633:toxicity; D015215:Zidovudine / Q000009:adverse effects* / Q000494:pharmacology / Q000633:toxicity
chemical_list: D004272:DNA, Mitochondrial; D018894:Reverse Transcriptase Inhibitors; D015215:Zidovudine
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