{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T13:28:57Z","timestamp":1787059737893,"version":"build-2736575974"},"reference-count":74,"publisher":"American Society for Microbiology","issue":"8","license":[{"start":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T00:00:00Z","timestamp":1787011200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T00:00:00Z","timestamp":1787011200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["PJT-159625"],"award-info":[{"award-number":["PJT-159625"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["HB1-164063"],"award-info":[{"award-number":["HB1-164063"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Canadian HIV Cure Enterprise","award":["BR4-197730"],"award-info":[{"award-number":["BR4-197730"]}]},{"name":"Martin Delaney \"REACH\" Collaboratory","award":["NIH grant 1-UM1AI164565-01"],"award-info":[{"award-number":["NIH grant 1-UM1AI164565-01"]}]},{"name":"sub-Saharan African Network for TB\/HIV Research Excellence (SANTHE), a DELTAS Africa Initiative","award":["DEL-15-006"],"award-info":[{"award-number":["DEL-15-006"]}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["J Virol"],"published-print":{"date-parts":[[2026,8,18]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>Superinfection, where a person with HIV acquires a second phylogenetically distinct strain, provides an opportunity to study reservoir evolutionary dynamics because the two strains can be tracked over time. We hereby characterize such a case that originally went undetected by clinical monitoring. The participant, who expressed the protective HLA-B*57:03 allele, initially controlled his subtype B infection but lost control after superinfection with a unique recombinant form (URF), which came to dominate in plasma without displacing the original B strain. Five years after initiating therapy, replication-competent proviruses from both strains persisted in blood, though URF proviruses dominated (80%). Despite their unequal representation within the reservoir, both strains rapidly rebounded upon treatment interruption, though most rebounding sequences belonged to a URF subclade that predated ART initiation. During the treatment interruption, genetically distinct viral lineages continually appeared in plasma, consistent with sequential \u201cwaves\u201d of reactivation of diverse reservoir clones. Notably, immune escape variants emerged from the reservoir in a later \u201cwave,\u201d displacing initial susceptible variants and underscoring the important role of immune responses in shaping rebound dynamics. Sequence analysis revealed that the URF transmitted\/founder virus already harbored key HLA-B*57:03-associated escape mutations, likely explaining the loss of viral control after superinfection. Our results reveal that superinfection can remain undetected despite routine HIV clinical monitoring, pre-adaptation of the superinfecting strain to host HLA can undermine immune control, immune-escaped virus can re-emerge from reservoirs during treatment interruption, and immune responses can actively shape viral rebound dynamics.<\/jats:p>\n                    <jats:sec>\n                      <jats:title>IMPORTANCE<\/jats:title>\n                      <jats:p>This case demonstrates that HIV superinfection can go undetected by routine clinical monitoring, underscoring the importance of assays that capture HIV diversity\u2014particularly those used to screen participants for cure trials. It also illustrates how pre-adaptation of a superinfecting strain to host HLA-restricted immune responses can evade existing immunity, with implications for understanding natural immune control, and underscoring the challenge of viral diversity for vaccine and immunotherapy design. The sequential emergence of genetically diverse HIV lineages during treatment interruption, including minority immune-escape variants that emerge from the reservoir to displace the initial susceptible population, highlights the difficulty of predicting rebound viral composition and underscores the key role of immune responses in shaping rebound dynamics. Critically, escaped rebound variants can then reseed the reservoir, thereby enriching it in escaped forms, highlighting a specific vulnerability for cure approaches that harness natural immune responses to eliminate reservoir cells.<\/jats:p>\n                    <\/jats:sec>\n                  <\/jats:sec>","DOI":"10.1128\/jvi.00473-26","type":"journal-article","created":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T14:01:49Z","timestamp":1783692109000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":0,"title":["HIV superinfection reveals sequential reservoir reactivation and immune-driven rebound dynamics"],"prefix":"10.1128","volume":"100","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0940-7512","authenticated-orcid":true,"given":"F. Harrison","family":"Omondi","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/0213rcc28","id-type":"ROR","asserted-by":"publisher"}],"name":"Faculty of Health Sciences, Simon Fraser University","place":["Burnaby, Canada"]},{"name":"British Columbia Centre for Excellence in HIV\/AIDS","place":["Vancouver, Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aniqa","family":"Shahid","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/0213rcc28","id-type":"ROR","asserted-by":"publisher"}],"name":"Faculty of Health Sciences, Simon Fraser University","place":["Burnaby, Canada"]},{"name":"British Columbia Centre for Excellence in HIV\/AIDS","place":["Vancouver, Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalie N.","family":"Kinloch","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/0213rcc28","id-type":"ROR","asserted-by":"publisher"}],"name":"Faculty of Health Sciences, Simon Fraser University","place":["Burnaby, Canada"]},{"name":"British Columbia Centre for Excellence in HIV\/AIDS","place":["Vancouver, Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Winnie","family":"Dong","sequence":"additional","affiliation":[{"name":"British Columbia Centre for Excellence in HIV\/AIDS","place":["Vancouver, Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maggie C.","family":"Duncan","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/0213rcc28","id-type":"ROR","asserted-by":"publisher"}],"name":"Faculty of Health Sciences, Simon Fraser University","place":["Burnaby, Canada"]},{"name":"British Columbia Centre for Excellence in HIV\/AIDS","place":["Vancouver, Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fatima","family":"Yaseen","sequence":"additional","affiliation":[{"name":"British Columbia Centre for Excellence in HIV\/AIDS","place":["Vancouver, Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evan","family":"Barad","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/0213rcc28","id-type":"ROR","asserted-by":"publisher"}],"name":"Faculty of Health Sciences, Simon Fraser University","place":["Burnaby, Canada"]},{"name":"British Columbia Centre for Excellence in HIV\/AIDS","place":["Vancouver, Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadia","family":"Moran-Garcia","sequence":"additional","affiliation":[{"name":"British Columbia Centre for Excellence in HIV\/AIDS","place":["Vancouver, Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1868-7579","authenticated-orcid":true,"given":"Amanda","family":"Cabral da Silva","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/0213rcc28","id-type":"ROR","asserted-by":"publisher"}],"name":"Faculty of Health Sciences, Simon Fraser University","place":["Burnaby, Canada"]},{"name":"British Columbia Centre for Excellence in HIV\/AIDS","place":["Vancouver, Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vitaliy","family":"Mysak","sequence":"additional","affiliation":[{"name":"British Columbia Centre for Excellence in HIV\/AIDS","place":["Vancouver, Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Don","family":"Kirkby","sequence":"additional","affiliation":[{"name":"British Columbia Centre for Excellence in HIV\/AIDS","place":["Vancouver, Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7369-1936","authenticated-orcid":true,"given":"Mario","family":"Ostrowski","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03dbr7087","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Immunology, University of Toronto","place":["Toronto, Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca M.","family":"Lynch","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00y4zzh67","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Microbiology, Immunology and Tropical Medicine, George Washington University","place":["Washington, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chanson J.","family":"Brumme","sequence":"additional","affiliation":[{"name":"British Columbia Centre for Excellence in HIV\/AIDS","place":["Vancouver, Canada"]},{"id":[{"id":"https:\/\/ror.org\/03rmrcq20","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Medicine, University of British Columbia","place":["Vancouver, Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Colin","family":"Kovacs","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/048sa9h54","id-type":"ROR","asserted-by":"publisher"}],"name":"Maple Leaf Clinic","place":["Toronto, Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4470-1231","authenticated-orcid":true,"given":"R. Brad","family":"Jones","sequence":"additional","affiliation":[{"name":"Infectious Disease Division, Department of Medicine, Weill Cornell Medical College","place":["New York, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guinevere Q.","family":"Lee","sequence":"additional","affiliation":[{"name":"Infectious Disease Division, Department of Medicine, Weill Cornell Medical College","place":["New York, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8157-1037","authenticated-orcid":true,"given":"Zabrina L.","family":"Brumme","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/0213rcc28","id-type":"ROR","asserted-by":"publisher"}],"name":"Faculty of Health Sciences, Simon Fraser University","place":["Burnaby, Canada"]},{"name":"British Columbia Centre for Excellence in HIV\/AIDS","place":["Vancouver, Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_5_2_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.278.5341.1295"},{"key":"e_1_3_5_3_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.278.5341.1291"},{"key":"e_1_3_5_4_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.94.24.13193"},{"key":"e_1_3_5_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm880"},{"key":"e_1_3_5_6_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.96.26.15109"},{"key":"e_1_3_5_7_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1414926112"},{"key":"e_1_3_5_8_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1802028115"},{"key":"e_1_3_5_9_2","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2021.719153"},{"key":"e_1_3_5_10_2","doi-asserted-by":"publisher","DOI":"10.1128\/mbio.02417-23"},{"key":"e_1_3_5_11_2","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.18889"},{"key":"e_1_3_5_12_2","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aaw5589"},{"key":"e_1_3_5_13_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1008286"},{"key":"e_1_3_5_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(13)70066-5"},{"key":"e_1_3_5_15_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiac166"},{"key":"e_1_3_5_16_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.292.10.1177"},{"key":"e_1_3_5_17_2","doi-asserted-by":"publisher","DOI":"10.1186\/1742-4690-4-67"},{"key":"e_1_3_5_18_2","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.37.7.2291-2296.1999"},{"key":"e_1_3_5_19_2","doi-asserted-by":"publisher","DOI":"10.1097\/QAD.0b013e3280f3c08a"},{"key":"e_1_3_5_20_2","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.00804-11"},{"key":"e_1_3_5_21_2","doi-asserted-by":"publisher","DOI":"10.1093\/ve\/vey030"},{"key":"e_1_3_5_22_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.710327"},{"key":"e_1_3_5_23_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-20442-3"},{"key":"e_1_3_5_24_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature03113"},{"key":"e_1_3_5_25_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1195271"},{"key":"e_1_3_5_26_2","doi-asserted-by":"publisher","DOI":"10.1093\/ve\/vev003"},{"key":"e_1_3_5_27_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm.4156"},{"key":"e_1_3_5_28_2","doi-asserted-by":"publisher","DOI":"10.3390\/v12020136"},{"key":"e_1_3_5_29_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20170193"},{"key":"e_1_3_5_30_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI93289"},{"key":"e_1_3_5_31_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI145254"},{"key":"e_1_3_5_32_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1256304"},{"key":"e_1_3_5_33_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1254194"},{"key":"e_1_3_5_34_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-39837-z"},{"key":"e_1_3_5_35_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01986-20"},{"key":"e_1_3_5_36_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiaa649"},{"key":"e_1_3_5_37_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.15.8869"},{"key":"e_1_3_5_38_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-018-0026-6"},{"key":"e_1_3_5_39_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2023.01.030"},{"key":"e_1_3_5_40_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-06843-5"},{"key":"e_1_3_5_41_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.06150-11"},{"key":"e_1_3_5_42_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.80.7.3617-3623.2006"},{"key":"e_1_3_5_43_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm992"},{"key":"e_1_3_5_44_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00286-10"},{"key":"e_1_3_5_45_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20031982"},{"key":"e_1_3_5_46_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.79.18.12100-12105.2005"},{"key":"e_1_3_5_47_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.174.12.7524"},{"key":"e_1_3_5_48_2","unstructured":"Los Alamos National Laboratory Sequence Database. Available from: https:\/\/www.hiv.lanl.gov"},{"key":"e_1_3_5_49_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20041455"},{"key":"e_1_3_5_50_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1008378"},{"key":"e_1_3_5_51_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-025-56116-1"},{"key":"e_1_3_5_52_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1005000"},{"key":"e_1_3_5_53_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2019.08.003"},{"key":"e_1_3_5_54_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1011755"},{"key":"e_1_3_5_55_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm.4100"},{"key":"e_1_3_5_56_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.0030177"},{"key":"e_1_3_5_57_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11538-007-9223-z"},{"key":"e_1_3_5_58_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0906822106"},{"key":"e_1_3_5_59_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0502522102"},{"key":"e_1_3_5_60_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.virol.2007.01.034"},{"key":"e_1_3_5_61_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btv120"},{"key":"e_1_3_5_62_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-019-0898-8"},{"key":"e_1_3_5_63_2","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.02490-21"},{"key":"e_1_3_5_64_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-10659-2"},{"key":"e_1_3_5_65_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkf436"},{"key":"e_1_3_5_66_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/17.5.415"},{"key":"e_1_3_5_67_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkh340"},{"key":"e_1_3_5_68_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btu531"},{"key":"e_1_3_5_69_2","doi-asserted-by":"publisher","DOI":"10.1093\/molbev\/msaa015"},{"key":"e_1_3_5_70_2","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.4285"},{"key":"e_1_3_5_71_2","doi-asserted-by":"publisher","DOI":"10.1111\/2041-210X.12628"},{"key":"e_1_3_5_72_2","doi-asserted-by":"publisher","DOI":"10.1089\/aid.1995.11.1413"},{"key":"e_1_3_5_73_2","doi-asserted-by":"publisher","DOI":"10.1086\/503914"},{"key":"e_1_3_5_74_2","doi-asserted-by":"publisher","DOI":"10.1038\/nbt1371"},{"key":"e_1_3_5_75_2","doi-asserted-by":"publisher","DOI":"10.1097\/QAD.0b013e32833e6cfb"}],"container-title":["Journal of Virology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/jvi.00473-26","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/jvi.00473-26","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T13:04:49Z","timestamp":1787058289000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/jvi.00473-26"}},"subtitle":[],"editor":[{"given":"Daniel","family":"Sauter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2026,8,18]]},"references-count":74,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2026,8,18]]}},"alternative-id":["10.1128\/jvi.00473-26"],"URL":"https:\/\/doi.org\/10.1128\/jvi.00473-26","relation":{},"ISSN":["0022-538X","1098-5514"],"issn-type":[{"value":"0022-538X","type":"print"},{"value":"1098-5514","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,18]]},"assertion":[{"value":"2026-03-21","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-05-26","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-07-10","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e00473-26"}}