PT - JOURNAL ARTICLE AU - Melissa-Rose Abrahams AU - Sarah B. Joseph AU - Nigel Garrett AU - Lynn Tyers AU - Matthew Moeser AU - Nancie Archin AU - Olivia D. Council AU - David Matten AU - Shuntai Zhou AU - Deelan Doolabh AU - Colin Anthony AU - Nilu Goonetilleke AU - Salim Abdool Karim AU - David M. Margolis AU - Sergei Kosakovsky Pond AU - Carolyn Williamson AU - Ronald Swanstrom TI - The Replication-Competent HIV-1 Latent Reservoir is Primarily Established Near the Time of Therapy Initiation AID - 10.1101/512475 DP - 2019 Jan 01 TA - bioRxiv PG - 512475 4099 - http://biorxiv.org/content/early/2019/01/04/512475.short 4100 - http://biorxiv.org/content/early/2019/01/04/512475.full AB - 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.One Sentence Summary Most of the long-lived, replication-competent HIV-1 reservoir is formed at the time of therapy initiation.