Genomic Damage in HIV-Uninfected Children with In Utero Zidovudine Exposure

Zidovudine (ZDV) is a nucleoside reverse transcriptase inhibitor (NRTI) which competitively inhibits HIV reverse transcriptase and is incorporated into the viral DNA, resulting in DNA chain termination. It was the first approved antiretroviral medication used for preventing HIV transmission from mother to child. However, in vitro and animal studies have suggested genotoxicity of ZDV and no study has evaluated potential impact of in utero ZDV exposure using genomic sequencing technologies. In this study, we investigate markers of genomic damage detected in peripheral blood mononuclear cell samples obtained from 91 ZDV-exposed and, for comparison, 94 NRTI-unexposed HIV-uninfected children born to HIV-infected mothers during the first week after birth. We utilize high-throughput DNA sequencing (whole exome sequencing) and genotype array methods to comprehensively identify potential clonal somatic single nucleotide variants (SNVs) and large acquired copy number alterations (SCNAs) related to ZDV exposure.]]>
ZDV-exposed children from SMARTT and NRTI-unexposed children from WITS were frequency-matched on sex, race, and maternal substance use status. 10 children were excluded due to insufficient DNA. Further examination revealed that 3 samples were contaminated. Additionally, 2 children were excluded due to discordant gender.]]>