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孕期接受核苷类逆转录酶抑制剂治疗的HIV感染女性的胎盘和脐带血线粒体DNA毒性

Placenta and cord blood mitochondrial DNA toxicity in HIV-infected women receiving nucleoside reverse transcriptase inhibitors during pregnancy.

作者信息

Shiramizu Bruce, Shikuma Kelsey M, Kamemoto Lori, Gerschenson Mariana, Erdem Guliz, Pinti Marcello, Cossarizza Andrea, Shikuma Cecilia

机构信息

University of Hawaii, Honolulu, Hawii, USA.

出版信息

J Acquir Immune Defic Syndr. 2003 Apr 1;32(4):370-4. doi: 10.1097/00126334-200304010-00004.

DOI:10.1097/00126334-200304010-00004
PMID:12640193
Abstract

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.

摘要

近期针对孕妇及动物模型的研究引发了人们对潜在严重线粒体毒性相关副作用的担忧,这些副作用可能出现在孕期接受核苷类逆转录酶抑制剂(NRTIs)以预防HIV-1围产期传播的母亲所生婴儿身上。本研究的目的是评估接受NRTI治疗的HIV感染孕妇与HIV阴性孕妇的脐带血和胎盘的线粒体DNA(mtDNA)含量,假设接受NRTI治疗的女性其胎盘和脐带血中每细胞的mtDNA拷贝数会减少。分娩后立即从8名接受NRTIs治疗的HIV感染孕妇和5名HIV阴性孕妇处获取胎盘和脐带血。通过定量实时PCR完成每细胞mtDNA拷贝数的评估。与HIV阴性女性相比,HIV感染女性胎盘每细胞的平均mtDNA拷贝数分别为152±119和880±136(P = 0.0016)。同样,与HIV阴性女性相比,HIV阳性女性脐带血每细胞的平均mtDNA拷贝数分别为144±101和865±331(P = 0.0026)。与HIV阴性女性相比,接受NRTIs治疗的HIV感染女性的胎盘和脐带血中每细胞的mtDNA拷贝数有统计学显著下降。需要进一步研究以更好地了解接受NRTI治疗以预防HIV垂直传播的婴儿和母亲的发病情况。

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