{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,2]],"date-time":"2026-11-02T12:14:02Z","timestamp":1793621642814,"version":"4.5.0"},"reference-count":27,"publisher":"Oxford University Press (OUP)","issue":"8","license":[{"start":{"date-parts":[[2022,3,2]],"date-time":"2022-03-02T00:00:00Z","timestamp":1646179200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P01 AI131385"],"award-info":[{"award-number":["P01 AI131385"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 AI106408"],"award-info":[{"award-number":["R01 AI106408"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 DA055491"],"award-info":[{"award-number":["R01 DA055491"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["DP2 DA051915"],"award-info":[{"award-number":["DP2 DA051915"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Pendleton Charitable Trust"},{"name":"San Diego Center for AIDS Research","award":["P30 AI036214"],"award-info":[{"award-number":["P30 AI036214"]}]},{"name":"San Diego Center for AIDS Research","award":["R01 MH128153"],"award-info":[{"award-number":["R01 MH128153"]}]},{"name":"San Diego Center for AIDS Research","award":["R01 DK131532"],"award-info":[{"award-number":["R01 DK131532"]}]},{"DOI":"10.13039\/100012802","name":"Ragon Institute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100012802","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,10,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Human immunodeficiency virus type 1 (HIV-1) sequence diversity and the presence of archived epitope muta\u00adtions in antibody binding sites are a major obstacle for the clinical application of broadly neutralizing antibodies (bNAbs) against HIV-1. Specifically, it is unclear to what degree the viral reservoir is compartmentalized and if virus susceptibility to antibody neutralization differs across tissues.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>The Last Gift cohort enrolled 7 people with HIV diagnosed with a terminal illness and collected antemortem blood and postmortem tissues across 33 anatomical compartments for near full-length env HIV genome sequencing. Using these data, we applied a Bayesian machine-learning model (Markov chain Monte Carlo\u2013support vector machine) that uses HIV-1 envelope sequences and approximated glycan-occupancy information to quantitatively predict the half-maximal inhib\u00aditory concentrations (IC50) of bNAbs, allowing us to map neutralization resistance pattern across tissue reservoirs.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Predicted mean susceptibilities across tissues within participants were relatively homogenous, and the susceptibility pattern observed in blood often matched what was predicted for tissues. However, selected tissues, such as the brain, showed ev\u00adidence of compartmentalized viral populations with distinct neutralization susceptibilities in some participants. Additionally, we found substantial heterogeneity in the range of neutralization susceptibilities across tissues within and between indi\u00adviduals, and between bNAbs within individuals (standard deviation of log2(IC50) &amp;gt;3.4).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Blood-based screening methods to determine viral susceptibility to bNAbs might underestimate the presence of resistant viral variants in tissues. The extent to which these resistant viruses are clinically relevant, that is, lead to bNAb therapeutic failure, needs to be further explored.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/cid\/ciac164","type":"journal-article","created":{"date-parts":[[2022,3,1]],"date-time":"2022-03-01T20:10:34Z","timestamp":1646165434000},"page":"1342-1350","source":"Crossref","is-referenced-by-count":10,"title":["Landscape of Human Immunodeficiency Virus Neutralization Susceptibilities Across Tissue Reservoirs"],"prefix":"10.1093","volume":"75","author":[{"given":"Chuangqi","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Biological Engineering, Massachusetts Institute of Technology , Cambridge, Massachusetts , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy E","family":"Schlub","sequence":"additional","affiliation":[{"name":"University of Sydney, Faculty of Medicine and Health, Sydney School of Public Health , Sydney, New South Wales , Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen Han","family":"Yu","sequence":"additional","affiliation":[{"name":"Bill & Melinda Gates Medical Research Institute , Cambridge, Massachusetts , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C Sabrina","family":"Tan","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center , Boston, Massachusetts , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karl","family":"Stefic","sequence":"additional","affiliation":[{"name":"Department of Virology, Tours University Hospital , Tours , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Gianella","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases and Global Public Health, University of California\u2013San Diego , San Diego, California , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Davey M","family":"Smith","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases and Global Public Health, University of California\u2013San Diego , San Diego, California , USA"},{"name":"VA San Diego Healthcare System , San Diego, California , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Douglas A","family":"Lauffenburger","sequence":"additional","affiliation":[{"name":"Department of Biological Engineering, Massachusetts Institute of Technology , Cambridge, Massachusetts , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antoine","family":"Chaillon","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases and Global Public Health, University of California\u2013San Diego , San Diego, California , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4687-9626","authenticated-orcid":false,"given":"Boris","family":"Julg","sequence":"additional","affiliation":[{"name":"Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, and Harvard University , Cambridge, Massachusetts , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2022,3,2]]},"reference":[{"key":"2022101219172185500_CIT0001","article-title":"Broadly neutralizing antibodies for HIV-1 prevention and therapy.","volume":"101475","author":"Julg","year":"2021","journal-title":"Semin Immunol"},{"key":"2022101219172185500_CIT0002","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1038\/nature14411","article-title":"Viraemia suppressed in HIV-1-infected humans by broadly neutralizing antibody 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