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Authors: Abrahams, Melissa-Rose and Joseph, Sarah B. and Garrett, Nigel and Tyers, Lynn and Moeser, Matthew and Archin, Nancie and Council, Olivia D. and Matten, David and Zhou, Shuntai and Doolabh, Deelan and Anthony, Colin and Goonetilleke, Nilu and Karim, Salim Abdool and Margolis, David M. and Kosakovsky Pond, Sergei and Williamson, Carolyn and Swanstrom, Ronald

Although antiretroviral therapy (ART) is highly effective at suppressing HIV-1 replication, the virus persists as a latent reservoir in resting CD4+ T cells during therapy. Little is known about the dynamics of reservoir formation, and this reservoir forms even when ART is initiated early after infection. The reservoir of individuals who initiate therapy in chronic infection is generally larger and genetically more diverse than that of individuals who initiate in acute infection, suggesting the reservoir is formed continuously throughout untreated infection. To determine when viruses enter the latent reservoir, we compared sequences of replication-competent viruses from resting CD4+ T cells from nine women on therapy to viral sequences circulating in blood collected longitudinally prior to therapy. We found that 78% of viruses from the latent reservoir were most genetically similar to viruses replicating just prior to therapy initiation. This proportion is far greater than expected if the reservoir forms continuously and is always long-lived. Thus, therapy alters the host environment in a way that allows the formation of a majority of the long-lived latent HIV-1 reservoir.

Journal: BioRxiv
DOI: 10.1101/512475
Year: 2019

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