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

Youjin Wang, Sean S Brummel, Erin Beilstein-Wedel, Casey L Dagnall, Rohan Hazra, Deborah Kacanek, Ellen G Chadwick, Carmen J Marsit, Stephen J Chanock, Sharon A Savage, Miriam C Poirier, Mitchell J Machiela, Eric A Engels, Pediatric HIV/AIDS Cohort Study, Youjin Wang, Sean S Brummel, Erin Beilstein-Wedel, Casey L Dagnall, Rohan Hazra, Deborah Kacanek, Ellen G Chadwick, Carmen J Marsit, Stephen J Chanock, Sharon A Savage, Miriam C Poirier, Mitchell J Machiela, Eric A Engels, Pediatric HIV/AIDS Cohort Study

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.

Conflict of interest statement

POTENTIAL CONFLICTS OF INTEREST

All authors: No potential conflicts of interest

Figures

Figure 1.. Association of relative telomere length…
Figure 1.. Association of relative telomere length at birth with zidovudine exposure in utero and mother’s HIV RNA level during pregnancy
a. Associations between relative telomere length at birth and zidovudine exposure in utero. Horizontal bars denote mean relative telomere length values. b. Associations between relative telomere length at birth and mother’s last HIV RNA level during pregnancy for all subjects. RNA level data were log10 transformed. c. Associations between relative telomere length at birth and mother’s last HIV RNA level during pregnancy according to in utero zidovudine exposure status. RNA level data were log10 transformed. Closed circle/solid line: ZDV-exposed, open circle/dotted line: ART-unexposed.

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Source: PubMed

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