biostudies-literatureUnknownKing IVNIAID NIH HHSNCI NIH HHSGates FoundationThe vast majority of persons living with HIV-1 who discontinue antiretroviral therapy (ART) demonstrate viral rebound, but the tissue-level events that lead to rebound viremia are poorly understood. Here we report the origin, dynamics, and correlates of viral rebound in 16 rhesus macaques (RMs) infected with molecularly barcoded SIVmac239M, treated with ART for 70 weeks, and necropsied on day 12 after ART discontinuation. Barcode analysis of plasma following ART discontinuation identified 1 to 38 rebounding barcode-defined viral lineages per animal, with 1 to 4 rebounding lineages contributing to first measurable rebound viremia. Analysis of barcode viral RNA (vRNA) expression in necropsy tissues revealed presumptive anatomic origin sites for 56 of 175 total rebounding viral lineages, withbioRxiv : the preprint server for biology2025.08.30.673277https://www.ebi.ac.uk/biostudies/studies/S-EPMC12407973biostudies-literatureOrigin and Correlates of Viral Rebound in SIV-Infected Rhesus Macaques Following ART Discontinuation.PMC12407973INV-002377UM1 AI164556R01 AI149670P01 AI17768775N91019D00024UM1 AI164560P01 AI169615Lifson JDBorducchi ENGoodman CABarouch DHKeele BFKing IVAid MImmonen TTWalker-Sperling VEKPicker LJKose EFerguson MJColarusso AGeleziunas RFennessey CMRinaldi WJfalseOrigin and Correlates of Viral Rebound in SIV-Infected Rhesus Macaques Following ART Discontinuation.The vast majority of persons living with HIV-1 who discontinue antiretroviral therapy (ART) demonstrate viral rebound, but the tissue-level events that lead to rebound viremia are poorly understood. Here we report the origin, dynamics, and correlates of viral rebound in 16 rhesus macaques (RMs) infected with molecularly barcoded SIVmac239M, treated with ART for 70 weeks, and necropsied on day 12 after ART discontinuation. Barcode analysis of plasma following ART discontinuation identified 1 to 38 rebounding barcode-defined viral lineages per animal, with 1 to 4 rebounding lineages contributing to first measurable rebound viremia. Analysis of barcode viral RNA (vRNA) expression in necropsy tissues revealed presumptive anatomic origin sites for 56 of 175 total rebounding viral lineages, with2025-01-01T00:00:00Z2025 Aug2026-04-23T03:13:25.385Z2026-04-23T03:09:38.587ZS-EPMC124079734090970610.1101/2025.08.30.673277