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Immunol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>High HIV viral load (VL) is associated with increased transmission risk and faster disease progression. HIV controllers achieve viral suppression without antiretroviral (ARV) treatment. We evaluated viremic control in a community-randomized trial with &amp;gt;48,000 participants.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A massively multiplexed antibody profiling system, VirScan, was used to quantify pre- and post-infection antibody reactivity to HIV peptides in 664 samples from 429 participants (13 controllers, 135 viremic non-controllers, 64 other non-controllers, 217 uninfected persons). Controllers had VLs &amp;lt;2,000 copies\/mL with no ARV drugs detected at the first HIV-positive visit and one year later. Viremic non-controllers had VLs 2,000 copies\/mL with no ARV drugs detected at the first HIV-positive visit. Other non-controllers had either ARV drugs detected at the first HIV-positive visit (n=47) or VLs &amp;lt;2,000 copies\/mL with no ARV drugs detected at only one HIV-positive visit (n=17).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We identified pre-infection HIV antibody reactivities that correlated with post-infection VL. Pre-infection reactivity to an epitope in the HR2 domain of gp41 was associated with controller status and lower VL. Pre-infection reactivity to an epitope in the C2 domain of gp120 was associated with non-controller status and higher VL. Different patterns of antibody reactivity were observed over time for these two epitopes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>These studies suggest that pre-infection HIV antibodies are associated with controller status and modulation of HIV VL. These findings may inform research on antibody-based interventions for HIV treatment.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2023.1178520","type":"journal-article","created":{"date-parts":[[2023,9,6]],"date-time":"2023-09-06T17:42:54Z","timestamp":1694022174000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Comprehensive profiling of pre-infection antibodies identifies HIV targets associated with viremic control and viral load"],"prefix":"10.3389","volume":"14","author":[{"given":"Wendy","family":"Grant-McAuley","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"William","family":"Morgenlander","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sarah E.","family":"Hudelson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Manjusha","family":"Thakar","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Estelle","family":"Piwowar-Manning","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"William","family":"Clarke","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Autumn","family":"Breaud","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joel","family":"Blankson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ethan","family":"Wilson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Helen","family":"Ayles","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter","family":"Bock","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ayana","family":"Moore","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Barry","family":"Kosloff","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kwame","family":"Shanaube","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sue-Ann","family":"Meehan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anneen","family":"van Deventer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sarah","family":"Fidler","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard","family":"Hayes","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ingo","family":"Ruczinski","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kai","family":"Kammers","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Oliver","family":"Laeyendecker","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"H. 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