In-utero exposure to zidovudine-containing antiretroviral therapy and clonal hematopoiesis in HIV-exposed uninfected newborns.

Autor:	Lin SH; Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville., Wang Y; Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville., Hartley SW; Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville., Karyadi DM; Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville., Lee OW; Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville., Zhu B; Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville., Zhou W; Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville.; Cancer Genomics Research Laboratory, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, Maryland., Brown DW; Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville., Beilstein-Wedel E; Center for Biostatistics in AIDS Research, Harvard T.H. Chan School of Public Health, Boston, Massachusetts., Hazra R; Maternal and Pediatric Infectious Disease Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland., Kacanek D; Center for Biostatistics in AIDS Research, Harvard T.H. Chan School of Public Health, Boston, Massachusetts., Chadwick EG; Department of Pediatrics, Feinberg School of Medicine, Northwestern University, Chicago, Illinois., Marsit CJ; Departments of Environmental Health and Epidemiology, Rollins School of Public Health, Emory University, Atlanta, Georgia., Poirier MC; Carcinogen-DNA Interactions Section, Laboratory of Cancer Biology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA., Brummel SS; Center for Biostatistics in AIDS Research, Harvard T.H. Chan School of Public Health, Boston, Massachusetts., Chanock SJ; Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville., Engels EA; Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville., Machiela MJ; Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville.
Jazyk:	angličtina
Zdroj:	AIDS (London, England) [AIDS] 2021 Aug 01; Vol. 35 (10), pp. 1525-1535.
DOI:	10.1097/QAD.0000000000002894
Abstrakt:	Objective: Zidovudine (ZDV) has been extensively used in pregnant women to prevent vertical transmission of HIV but few studies have evaluated potential mutagenic effects of ZDV during fetal development. Design: Our study investigated clonal hematopoiesis in HIV-exposed uninfected (HEU) newborns, 94 of whom were ZDV-exposed and 91 antiretroviral therapy (ART)-unexposed and matched for potential confounding factors. Methods: Utilizing high depth sequencing and genotyping arrays, we comprehensively examined blood samples collected during the first week after birth for potential clonal hematopoiesis associated with fetal ZDV exposure, including clonal single nucleotide variants (SNVs), small insertions and deletions (indels), and large structural copy number or copy neutral alterations. Results: We observed no statistically significant difference in the number of SNVs and indels per person in ZDV-exposed children (adjusted ratio [95% confidence interval, CI] for expected number of mutations = 0.79 [0.50--1.22], P = 0.3), and no difference in the number of large structural alterations. Mutations in common clonal hematopoiesis driver genes were not found in the study population. Mutational signature analyses on SNVs detected no novel signatures unique to the ZDV-exposed children and the mutational profiles were similar between the two groups. Conclusion: Our results suggest that clonal hematopoiesis at levels detectable in our study is not strongly influenced by in-utero ZDV exposure; however, additional follow-up studies are needed to further evaluate the safety and potential long-term impacts of in-utero ZDV exposure in HEU children as well as better investigate genomic aberrations occurring late in pregnancy. (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)
Databáze:	MEDLINE
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