子宫内暴露于齐多夫定的抗逆转录病毒治疗与出生时白细胞端粒长度的关系。

Association between zidovudine-containing antiretroviral therapy exposure in utero and leukocyte telomere length at birth.

机构信息

aDivision of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland bCenter for Biostatistics in AIDS Research, Harvard T.H. Chan School of Public Health, Boston, Massachusetts cCancer Genomics Research Laboratory, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, Maryland dMaternal and Pediatric Infectious Disease Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland eDepartment of Pediatrics, Feinberg School of Medicine, Northwestern University, Chicago, Illinois fDepartment of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, Georgia gCarcinogen-DNA Interactions Section, Laboratory of Cancer Biology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.

出版信息

AIDS. 2019 Nov 1;33(13):2091-2096. doi: 10.1097/QAD.0000000000002317.

DOI:10.1097/QAD.0000000000002317

PMID:31335808

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6774838/

Abstract

OBJECTIVES

Zidovudine (ZDV) is a nucleoside reverse transcriptase inhibitor that could cause telomere shortening through inhibition of telomerase. We examined the association between in utero exposure to ZDV and telomere length at birth in HIV-exposed-uninfected (HEU) newborns.

METHODS

We selected 94 ZDV-exposed HEU children and 85 antiretroviral therapy (ART)-unexposed HEU children from the Surveillance Monitoring for ART Toxicities Study and the Women and Infants Transmission Study. We assessed relative telomere length in stored peripheral blood mononuclear cells taken in the first 7 days of life using quantitative polymerase chain reaction. We used linear regression to compare relative telomere length between ZDV-exposed and ART-unexposed children. We additionally evaluated relative telomere length according to maternal and infant characteristics.

RESULTS

Relative telomere length was longer in ZDV-exposed children compared with ART-unexposed individuals (adjusted mean ratio difference 0.21, 95% confidence interval 0.15-0.28, P < 0.001). We found an inverse correlation between maternal HIV RNA levels and infant relative telomere length (-0.06 per log10 copies, 95% confidence interval -0.08 to -0.03, P < 0.001). Relative telomere length was not associated with maternal CD4 cell count, maternal age, gestational age, sex, sample storage time, or maternal substance use (P > 0.05).

CONCLUSION

Relative telomere length was longer in ZDV-exposed infants. This difference may reflect beneficial health effects of ART during pregnancy, as we observed an inverse association with maternal HIV RNA levels.

摘要

目的

齐多夫定（ZDV）是一种核苷逆转录酶抑制剂，可通过抑制端粒酶导致端粒缩短。我们研究了 HIV 暴露但未感染（HEU）新生儿在子宫内暴露于 ZDV 与出生时端粒长度之间的关系。

方法

我们从监测抗逆转录病毒治疗毒性研究和妇女与婴儿传播研究中选择了 94 名 ZDV 暴露的 HEU 儿童和 85 名未接受抗逆转录病毒治疗（ART）的 HEU 儿童。我们使用定量聚合酶链反应评估了在生命的头 7 天内采集的储存外周血单核细胞中的相对端粒长度。我们使用线性回归比较了 ZDV 暴露和 ART 未暴露儿童之间的相对端粒长度。我们还根据母婴特征评估了相对端粒长度。

结果

与 ART 未暴露个体相比，ZDV 暴露儿童的相对端粒长度更长（调整后的平均比值差异 0.21，95%置信区间 0.15-0.28，P<0.001）。我们发现母婴 HIV RNA 水平与婴儿相对端粒长度呈负相关（每 log10 个拷贝减少 0.06，95%置信区间-0.08 至-0.03，P<0.001）。相对端粒长度与母婴 CD4 细胞计数、母婴年龄、胎龄、性别、样本储存时间或母婴物质使用无关（P>0.05）。