Côté Hélène C F, Raboud Janet, Bitnun Ari, Alimenti Ariane, Money Deborah M, Maan Evelyn, Costei Adriana, Gadawski Izabelle, Diong Christina, Read Stanley, Shen Sandy, Harrigan P Richard, Burdge David R, King Susan M, Forbes John C
Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, Canada.
J Infect Dis. 2008 Sep 15;198(6):851-9. doi: 10.1086/591253.
The effects of perinatal antiretroviral therapy (ART) on infant mitochondrial function are not well known. We compared blood mitochondrial DNA (mtDNA) levels and mtDNA gene expression (mtRNA) in human immunodeficiency virus (HIV)-uninfected, ART-exposed infants born to HIV-positive mothers with mtDNA levels and mtDNA gene expression in control infants born to uninfected women.
In this prospective cohort study, longitudinal mtDNA:nuclear DNA and mtRNA:beta-actin mRNA ratios were compared in blood samples obtained at various time points from birth to 8 months, using generalized estimating equation linear regression models.
Log(10) mtDNA levels at birth were higher in ART-exposed infants, compared with levels in control infants, although the difference did not reach statistical significance (P = .07 for comparison of samples obtained 0-3 days after birth). ART-exposed infants' mtDNA levels increased further during the zidovudine prophylaxis period-from age 4 days to age 6 weeks-(P = .001) and remained significantly higher than the levels observed in control infants until the end of the study. In contrast, log(10) mtRNA levels at birth were lower in ART-exposed infants than in control infants (P = .03), but were not statistically different later.
When control infants and ART-exposed infants were compared, the mtDNA level was increased but mitochondrial gene expression was decreased in ART-exposed infants. These differences persisted after zidovudine was discontinued, suggesting that changes in mitochondrial proliferation and/or expression take place during and after ART exposure. These changes are likely the effects of the antiretroviral drugs on mitochondria. The clinical relevance and long-term impact of these alterations must be studied.
围产期抗逆转录病毒疗法（ART）对婴儿线粒体功能的影响尚不清楚。我们比较了出生于HIV阳性母亲的未感染HIV但暴露于ART的婴儿与出生于未感染女性的对照婴儿的血液线粒体DNA（mtDNA）水平和mtDNA基因表达（mtRNA）。
在这项前瞻性队列研究中，使用广义估计方程线性回归模型，比较了从出生到8个月不同时间点采集的血液样本中纵向的mtDNA:核DNA和mtRNA:β-肌动蛋白mRNA比率。
与对照婴儿相比，暴露于ART的婴儿出生时的Log(10) mtDNA水平较高，尽管差异未达到统计学显著性（出生后0 - 3天采集的样本比较，P = 0.07）。暴露于ART的婴儿的mtDNA水平在齐多夫定预防期（从4天龄到6周龄）进一步升高（P = 0.001），并且直到研究结束时仍显著高于对照婴儿中观察到的水平。相比之下，暴露于ART的婴儿出生时的Log(10) mtRNA水平低于对照婴儿（P = 0.03），但之后在统计学上没有差异。
当比较对照婴儿和暴露于ART的婴儿时，暴露于ART的婴儿的mtDNA水平升高，但线粒体基因表达降低。在停用齐多夫定后这些差异仍然存在，表明线粒体增殖和/或表达的变化在ART暴露期间和之后发生。这些变化可能是抗逆转录病毒药物对线粒体的影响。必须研究这些改变的临床相关性和长期影响。
