{"doi":"10.1101/2024.03.27.24304867","title":"Rapid Biphasic Decay of Intact and Defective HIV DNA Reservoir During Acute Treated HIV Disease","abstract":"ABSTRACT Despite antiretroviral therapy (ART), HIV persists in latently-infected cells (“the reservoir”) which decay slowly over time. Here, leveraging >500 longitudinal samples from 67 people with HIV (PWH) treated during acute infection, we developed a novel mathematical model to predict reservoir decay from peripheral CD4+ T cells. Nonlinear generalized additive models demonstrated rapid biphasic decay of intact DNA (week 0-5: t 1/2 ∼2.83 weeks; week 5-24: t 1/2 ∼15.4 weeks) that extended out to 1 year. These estimates were ∼5-fold faster than prior decay estimates among chronic treated PWH. Defective DNA had a similar biphasic pattern, but data were more variable. Predicted intact and defective decay rates were faster for PWH with earlier timing of ART initiation, higher initial CD4+ T cell count, and lower pre-ART viral load. These data add to our limited understanding of HIV reservoir decay at the time of ART initiation, informing future curative strategies targeting this critical time.","journal":"medRxiv","year":2024,"id":485100,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":6,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9477,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1219798,"name":"Lei Shi","orcid":"0009-0004-4245-3478","position":1,"is_corresponding":false},{"id":828876,"name":"Junzhe Shao","orcid":null,"position":2,"is_corresponding":false},{"id":71690,"name":"Rebecca Hoh","orcid":"0000-0001-5112-4220","position":3,"is_corresponding":false},{"id":489748,"name":"Heather Hartig","orcid":null,"position":4,"is_corresponding":false},{"id":807186,"name":"Vivian Pae","orcid":null,"position":5,"is_corresponding":false},{"id":806362,"name":"Sannidhi Sarvadhavabhatla","orcid":"0009-0003-8326-8423","position":6,"is_corresponding":false},{"id":1220304,"name":"Sophia Donaire","orcid":null,"position":7,"is_corresponding":false},{"id":1219799,"name":"Caroline Sheikhzadeh","orcid":"0009-0000-2631-9827","position":8,"is_corresponding":false},{"id":228707,"name":"Jeffrey M. Milush","orcid":"0000-0002-0773-6411","position":9,"is_corresponding":false},{"id":228711,"name":"Gregory M. Laird","orcid":"0000-0003-2873-4295","position":10,"is_corresponding":false},{"id":1220305,"name":"M. Mathias","orcid":null,"position":11,"is_corresponding":false},{"id":243447,"name":"Kristen D. Ritter","orcid":null,"position":12,"is_corresponding":false},{"id":228705,"name":"Michael J. Peluso","orcid":"0000-0003-0585-6230","position":13,"is_corresponding":false},{"id":239684,"name":"Jeffrey N. Martin","orcid":"0000-0002-9773-3256","position":14,"is_corresponding":false},{"id":286358,"name":"Frederick Hecht","orcid":"0000-0002-5782-1171","position":15,"is_corresponding":false},{"id":293287,"name":"Christopher D. Pilcher","orcid":null,"position":16,"is_corresponding":false},{"id":462119,"name":"Stephanie E. Cohen","orcid":"0000-0002-1632-1074","position":17,"is_corresponding":false},{"id":41005,"name":"Susan Buchbinder","orcid":"0000-0003-2404-0712","position":18,"is_corresponding":false},{"id":58746,"name":"Diane V. Havlir","orcid":"0000-0003-0761-3136","position":19,"is_corresponding":false},{"id":241509,"name":"Monica Gandhi","orcid":"0000-0002-7025-1994","position":20,"is_corresponding":false},{"id":239686,"name":"Timothy J. Henrich","orcid":"0000-0002-6684-0622","position":21,"is_corresponding":false},{"id":1219800,"name":"Hiroyu Hatano","orcid":"0000-0002-3606-0772","position":22,"is_corresponding":false},{"id":779147,"name":"Jingshen Wang","orcid":"0000-0002-1432-3834","position":23,"is_corresponding":false},{"id":71691,"name":"Steven G. Deeks","orcid":"0000-0001-6371-747X","position":24,"is_corresponding":false},{"id":75994,"name":"Sulggi A. 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