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

  1. Author:
    Wang, Youjin
    Brummel, Sean S
    Beilstein-Wedel, Erin
    Dagnall,Casey
    Hazra, Rohan
    Kacanek, Deborah
    Chadwick, Ellen G
    Marsit, Carmen J
    Chanock, Stephen J
    Savage, Sharon A
    Poirier, Miriam C
    Machiela, Mitchell J
    Engels, Eric A

  2. Author Address

    Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA., Center for Biostatistics in AIDS Research, Harvard T.H. Chan School of Public Health, Boston, MA, USA., Cancer Genomics Research Laboratory, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD, USA., Maternal and Pediatric Infectious Disease Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA., Department of Pediatrics, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA., Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, GA, USA., Carcinogen-DNA Interactions Section, Laboratory of Cancer Biology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA., Drs. Machiela and Engels contributed equally.,
    1. Year: 2019
    2. Date: NOV 1
    3. Epub Date: 2019 07 22
  2. Journal: AIDS (London, England)
    1. 33
    2. 13
    3. Pages: 2091-2096
  4. Type of Article: Article
  5. ISSN: 0269-9370
  1. 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 log(10) 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.

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External Sources

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  2. DOI: 10.1097/QAD.0000000000002317
  3. PMID: 31335808
  4. View record in Web of Science®
  5. WOS: 000507309100015

Library Notes

  1. Fiscal Year: FY2018-2019
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