title: Zidovudine exposure in HIV-1 infected Tanzanian women increases mitochondrial DNA levels in placenta and umbilical cords.
abstract: BACKGROUND
  Zidovudine (AZT) constitutes part of the recommended regimens for prevention and treatment of HIV-1 infection. At the same time, AZT as well as HIV-1 infection itself may induce mitochondrial damage. In this study, we analyzed the impact of prenatal AZT-exposure on mitochondrial alterations in HIV-infected women and their infants.
  
  
  METHODS
  Mitochondrial DNA (mtDNA) levels in placentas of HIV-1 infected Tanzanian women with and without prenatal AZT exposure, and in the umbilical cords of their AZT-exposed/unexposed infants were quantified using real-time PCR. Furthermore, we checked for the most common mitochondrial deletion in humans, the 4977 base pair deletion (dmtDNA4977) as a marker for mitochondrial stress.
  
  
  RESULTS
  83 women fulfilled the inclusion criteria. 30 women had been treated with AZT (median duration 56 days; IQR 43-70 days) while 53 women had not taken AZT during pregnancy. Baseline maternal characteristics in the two groups were similar. The median mtDNA levels in placentas and umbilical cords of women (311 copies/cell) and infants (190 copies/cell) exposed to AZT were significantly higher than in AZT-unexposed women (187 copies/cell; p = 0.021) and infants (127 copies/cell; p = 0.037). The dmtDNA4977 was found in placentas of one woman of each group and in 3 umbilical cords of AZT-unexposed infants but not in umbilical cords of AZT-exposed infants.
  
  
  CONCLUSIONS
  Antenatal AZT intake did not increase the risk for the common mitochondrial deletion dmtDNA4977. Our data suggests that AZT exposure elevates mtDNA levels in placentas and umbilical cords possibly by positively influencing the course of maternal HIV-1 infection.
authors: Institute of Tropical Medicine and International Health, Charité-Universitätsmedizin Berlin, Berlin, Germany.
authors: Andrea
authors: A
authors: Kunz
authors: Nicole
authors: N
authors: von Wurmb-Schwark
authors: Julius
authors: J
authors: Sewangi
authors: Judith
authors: J
authors: Ziske
authors: Inga
authors: I
authors: Lau
authors: Paulina
authors: P
authors: Mbezi
authors: Stefanie
authors: S
authors: Theuring
authors: Andrea
authors: A
authors: Hauser
authors: Festo
authors: F
authors: Dugange
authors: Angela
authors: A
authors: Katerna
authors: Gundel
authors: G
authors: Harms
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000494:pharmacology / Q000627:therapeutic use; D004272:DNA, Mitochondrial / Q000378:metabolism*; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000196:embryology* / Q000235:genetics / Q000378:metabolism; D015497:HIV-1 / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D007223:Infant; D008297:Male; D010920:Placenta / Q000187:drug effects* / Q000378:metabolism; D011247:Pregnancy; D013636:Tanzania; D014470:Umbilical Cord / Q000187:drug effects* / Q000378:metabolism; D055815:Young Adult; D015215:Zidovudine / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D019380:Anti-HIV Agents; D004272:DNA, Mitochondrial; D015215:Zidovudine