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ABSTRACT The latent HIV reservoir forms early in the course of infection and is maintained for life despite effective antiretroviral treatment (ART), including early treatment. Perinatal HIV infection presents a unique opportunity to limit seeding of the reservoir through early ART. However, a greater understanding of the persistence of the integrated proviruses is needed for targeting the residual proviruses that form barriers to cure. A study was performed by Bale and Katusiime et al. (M. J. Bale, M. G. Katusiime, D. Wells, X. Wu, et al., mBio 12:e00568-21, 2021, https://doi.org/10.1128/mBio.00568-21) using in-depth integration site analysis in 11 children before ART and after up to nine years of ART. They have identified early development of long-lived proviruses, although the replication competence is unknown. A small fraction of cells bearing integrated proviruses clonally expand early during infection and persist. Integration in the oncogenes STAT5B and BACH2 were also found; these findings confirm the early development of clonal proliferation in perinatal HIV infection despite early effective ART, with a propensity for oncogenes.