While the successes achieved in decreasing MTCT are extraordinary, there is still a concern that in utero ART causes mitochondrial toxicity [20]. Many of the NRTIs used in reducing MTCT are NRTIs, including ZDV, which are well known to cause mitochondrial toxicity in adults [21], especially with prolonged exposure [22]. Because NRTIs cross the placenta [23], mitochondrial toxicity is a concern in infants
who have been exposed to them in utero. While studies have shown that clinically apparent disease is rare [4–6,24], many human and primate studies have shown biochemical and histological changes suggestive of mitochondrial toxicity in ART-exposed infants [2–10,12,13,17,20,23,25–27]. However, the exact changes observed, especially in mtDNA content and mitochondrial enzyme expression, vary significantly depending SB431542 on the tissue and cell types analysed, the methods used, and the timing of the collection of samples. In our study, we systematically evaluated mtDNA content in placenta, umbilical cord blood and peripheral infant blood, which had not been previously done, and evaluated mitochondrial enzyme expression level (as an indirect measure of mitochondrial function) in cord blood and infant peripheral blood in HIV-positive/HIV-exposed maternal–infant pairs compared with uninfected controls.
We also evaluated placental oxidative stress levels for the first time. Interestingly, while placental find more measurements were all similar between Cyclooxygenase (COX) groups, umbilical cord blood and peripheral infant blood showed significant differences between groups. In umbilical cord blood, mtDNA content was similar between groups but mitochondrial enzyme expression level was significantly decreased in
the HIV-positive/HIV-exposed group. In contrast, infant mitochondrial enzyme expression level was similar between groups, but mtDNA content was significantly increased in the peripheral blood of the HIV-exposed infants. In regression analyses, the significant changes in enzyme expression and mtDNA in the cord and infant blood, respectively, were most associated with HIV/ART exposure. Increased mtDNA content in the infants was also associated with increasing maternal age. While it may seem counterintuitive to observe increased mtDNA content in HIV/ART-exposed infants, these findings may suggest an in utero compensatory mechanism to overcome HIV/ART-associated mitochondrial toxicity. Specifically, the quantity of mtDNA may increase in the infant as HIV/ART exposure has caused a decrease in mitochondrial enzyme expression in the umbilical cord blood. This concept of in utero mtDNA proliferation in HIV/ART-exposed and HIV-infected infants is consistent with the findings of a few other studies [8,12,13,25,26]. Côté et al.