Zidovudine exposure in HIV-1 infected Tanzanian women increases mitochondrial DNA levels in placenta and umbilical cords

• Published in: PloS one 2012-07, Vol.7 (7), p.e41637
• Main Authors: Kunz, Andrea, von Wurmb-Schwark, Nicole, Sewangi, Julius, Ziske, Judith, Lau, Inga, Mbezi, Paulina, Theuring, Stefanie, Hauser, Andrea, Dugange, Festo, Katerna, Angela, Harms, Gundel
• Format: Article
• Language: English
• Subjects: Acquired immune deficiency syndrome; Adult; AIDS; Analysis; Anti-HIV Agents - pharmacology; Anti-HIV Agents - therapeutic use; Antiretroviral drugs; Biology; Care and treatment; Clonal deletion; Deoxyribonucleic acid; Disease transmission; DNA; DNA, Mitochondrial - metabolism; Exposure; Female; Gene deletion; HIV; HIV Infections - drug therapy; HIV Infections - embryology; HIV Infections - genetics; HIV Infections - metabolism; HIV-1 - drug effects; HIV-1 - physiology; Human immunodeficiency virus; Humans; Impact analysis; Impact damage; Infant; Infants; Infection; Infections; Male; Medicine; Mitochondrial DNA; Mutation; Newborn babies; Placenta; Placenta - drug effects; Placenta - metabolism; Pregnancy; Pregnant women; Prenatal experience; Prevention; Reverse transcriptase inhibitors; Tanzania; Umbilical cord; Umbilical Cord - drug effects; Umbilical Cord - metabolism; Umbilical cords; Womens health; Young Adult; Zidovudine; Zidovudine - pharmacology; Zidovudine - therapeutic use
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0041637

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. 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. 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. 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.