Insights from Clonal Expansion and HIV Persistence in Perinatal Infections

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.