Placenta and cord blood mitochondrial DNA toxicity in HIV-infected women receiving nucleoside reverse transcriptase inhibitors during pregnancy.
Recent studies of pregnant women and animal models have raised concerns regarding potentially serious mitochondrial toxicity-related side effects in infants born to mothers who received nucleoside reverse transcriptase inhibitors (NRTIs) during their pregnancy to prevent HIV-1 perinatal transmission. The aim of this study was to assess mitochondrial DNA (mtDNA) content of cord blood and placenta in HIV-infected pregnant women receiving NRTI compared with HIV-negative women, hypothesizing that placenta and cord blood mtDNA copies per cell would be decreased in women on NRTI therapy. Immediately following delivery, placenta and cord blood were obtained from eight HIV-infected pregnant women on NRTIs and five HIV-negative women. Assessment of mtDNA copies per cell was accomplished by quantitative real-time PCR. The mean mtDNA copies per cell from the placenta of the HIV-infected women compared with HIV-negative women was 152 +/- 119 and 880 +/- 136 ( =.0016), respectively. Similarly, the mean mtDNA copies per cell from the cord blood of the HIV-positive women compared with HIV-negative women was 144 +/- 101 and 865 +/- 331 ( =.0026), respectively. There was a statistically significant decrease in mtDNA copies per cell in placenta and cord blood between the HIV-infected women on NRTIs compared with HIV-negative women. Further studies are needed to better understand the morbidity to infants and mothers treated with NRTI to prevent vertical transmission of HIV.
Shiramizu
Bruce
B
University of Hawaii, Honolulu, Hawii, USA. bshirami@hawaii.edu
Shikuma
Kelsey M
KM
Kamemoto
Lori
L
Gerschenson
Mariana
M
Erdem
Guliz
G
Pinti
Marcello
M
Cossarizza
Andrea
A
Shikuma
Cecilia
C
D001483:Base Sequence; D017931:DNA Primers; D004272:DNA, Mitochondrial / Q000032:analysis / Q000235:genetics*; D005260:Female; D005312:Fetal Blood / Q000737:chemistry*; D015658:HIV Infections / Q000188:drug therapy* / Q000517:prevention & control / Q000635:transmission; D018023:HIV Seronegativity; D006801:Humans; D018445:Infectious Disease Transmission, Vertical / Q000517:prevention & control*; D008928:Mitochondria / Q000737:chemistry / Q000473:pathology*; D010920:Placenta / Q000473:pathology*; D016133:Polymerase Chain Reaction; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000188:drug therapy / Q000821:virology*; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use*; D015215:Zidovudine / Q000627:therapeutic use*
D017931:DNA Primers; D004272:DNA, Mitochondrial; D018894:Reverse Transcriptase Inhibitors; D015215:Zidovudine