771 Placenta and Cord Blood Mitochondrial DNA Toxicity in HIV-infected Women Receiving Nucleoside Reverse Transcriptase Inhibitors During Pregnancy B. Shiramizu*1, K. Shikuma2, L. Kamemoto1, M. Gerschenson1, G. Erdem1, M. Pinti3, A. Cossarizza3, C. Shikuma1 1Univ of Hawaii, Honolulu; 2Univ of Southern California, Los Angeles; and 3Univ of Modena and Reggio Emilia, Italy
Background: Recent studies in humans and animal models have raised concerns regarding potentially serious mitochondrial toxicity-related side effects in infants born to mothers receiving nucleoside reverse transcriptase inhibitors (NRTI) during pregnancy to prevent HIV transmission. The aim of the study was to assess mitochondrial DNA (mtDNA) content of placenta and cord blood in HIV-infected pregnant women receiving NRTI compared to HIV-negative women, hypothesizing that placenta and cord blood mtDNA copies per cell would be decreased in women on NRTI.
Methods: Informed consent was obtained as per guidelines by the local Institutional Review Boards prior to delivery. Following delivery, placenta and cord blood were obtained from 8 HIV-infected pregnant women on NRTI and 5 HIV-negative women. Assessment of mtDNA copies per cell was accomplished by quantitative real-time PCR. Statistical analysis was performed using the Wilcoxon Rank-sum, 2-sided test to determine the difference in mtDNA levels between NRTI exposed HIV-positive specimens and HIV negative specimens.
Results: The mean mtDNA copies per cell from placenta of HIV-infected women compared to HIV-negative women was 52 ±119 and 880 ±136 (p = 0.0016), respectively. Similarly, from cord blood, the mean mtDNA copies per cell was 144 ±101 and 865 ±331 (p = 0.0026) of HIV-positive and negative women, respectively. There was a statistically significant difference between the HIV-infected women on NRTI compared to HIV-negative women.
Conclusions: Current information from clinical studies does not support clinically relevant acute mitochondrial toxicity in the newborn exposed in utero to NRTI, but the data presented here and in previous studies in monkeys suggest that at the tissue level, mitochondrial toxicity does occur. While neonatal toxicities may not be immediately evident, consequences of long-term morbidity are still unknown and the pathophysiology of mitochondrial toxicity in utero may be due to a number of factors. Further studies are needed to better understand the morbidity to infants and mothers treated with NRTI to prevent vertical transmission of HIV.