{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,18]],"date-time":"2026-04-18T01:20:36Z","timestamp":1776475236150,"version":"3.51.2"},"update-to":[{"DOI":"10.1371\/journal.pcbi.1010003","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2022,5,9]],"date-time":"2022-05-09T00:00:00Z","timestamp":1652054400000}}],"reference-count":38,"publisher":"Public Library of Science (PLoS)","issue":"4","license":[{"start":{"date-parts":[[2022,4,6]],"date-time":"2022-04-06T00:00:00Z","timestamp":1649203200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["K25 AI155224"],"award-info":[{"award-number":["K25 AI155224"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["UM1 AI068614"],"award-info":[{"award-number":["UM1 AI068614"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["UM1 AI068635"],"award-info":[{"award-number":["UM1 AI068635"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000865","name":"Bill and Melinda Gates Foundation","doi-asserted-by":"publisher","award":["OPP1151646"],"award-info":[{"award-number":["OPP1151646"]}],"id":[{"id":"10.13039\/100000865","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.ploscompbiol.org"],"crossmark-restriction":false},"short-container-title":["PLoS Comput Biol"],"abstract":"<jats:p>\n                    Broadly neutralizing antibodies (bNAbs) are promising agents to prevent HIV infection and achieve HIV remission without antiretroviral therapy (ART). As with ART, bNAb combinations are likely needed to cover HIV\u2019s extensive diversity. Not all bNAbs are identical in terms of their breadth, potency, and\n                    <jats:italic>in vivo<\/jats:italic>\n                    longevity (half-life). Given these differences, it is important to optimally select the composition, or dose ratio, of combination bNAb therapies for future clinical studies. We developed a model that synthesizes 1) pharmacokinetics, 2) potency against a wide HIV diversity, 3) interaction models for how drugs work together, and 4) correlates that translate\n                    <jats:italic>in vitro<\/jats:italic>\n                    potency to clinical protection. We found optimization requires drug-specific balances between potency, longevity, and interaction type. As an example, tradeoffs between longevity and potency are shown by comparing a combination therapy to a bi-specific antibody (a single protein merging both bNAbs) that takes the better potency but the worse longevity of the two components. Then, we illustrate a realistic dose ratio optimization of a triple combination of VRC07, 3BNC117, and 10\u20131074 bNAbs. We apply protection estimates derived from both a non-human primate (NHP) challenge study meta-analysis and the human antibody mediated prevention (AMP) trials. In both cases, we find a 2:1:1 dose emphasizing VRC07 is nearly optimal. Our approach can be immediately applied to optimize the next generation of combination antibody prevention and cure studies.\n                  <\/jats:p>","DOI":"10.1371\/journal.pcbi.1010003","type":"journal-article","created":{"date-parts":[[2022,4,6]],"date-time":"2022-04-06T13:55:24Z","timestamp":1649253324000},"page":"e1010003","update-policy":"https:\/\/doi.org\/10.1371\/journal.pcbi.corrections_policy","source":"Crossref","is-referenced-by-count":26,"title":["Optimizing clinical dosing of combination broadly neutralizing antibodies for HIV prevention"],"prefix":"10.1371","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2258-5276","authenticated-orcid":true,"given":"Bryan T.","family":"Mayer","sequence":"first","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1404-4322","authenticated-orcid":true,"given":"Allan C.","family":"deCamp","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1546-6172","authenticated-orcid":true,"given":"Yunda","family":"Huang","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2598-1621","authenticated-orcid":true,"given":"Joshua T.","family":"Schiffer","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3867-0232","authenticated-orcid":true,"given":"Raphael","family":"Gottardo","sequence":"additional","affiliation":[]},{"given":"Peter B.","family":"Gilbert","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5684-9538","authenticated-orcid":true,"given":"Daniel 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Antibodies","volume":"160","author":"S Wang","year":"2015","journal-title":"Cell [Internet]."},{"issue":"1","key":"pcbi.1010003.ref004","article-title":"Basis and Statistical Design of the Passive HIV-1 Antibody Mediated Prevention (AMP) Test-of-Concept Efficacy Trials.","volume":"9","author":"PB Gilbert","year":"2017","journal-title":"Stat Commun Infect Dis [Internet]."},{"issue":"11","key":"pcbi.1010003.ref005","doi-asserted-by":"crossref","first-page":"1003","DOI":"10.1056\/NEJMoa2031738","article-title":"Two Randomized Trials of Neutralizing Antibodies to Prevent HIV-1 Acquisition","volume":"384","author":"L Corey","year":"2021","journal-title":"N Engl J Med [Internet]."},{"issue":"1","key":"pcbi.1010003.ref006","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1186\/s12915-018-0544-1","article-title":"Viral diversity is an obligate consideration in CRISPR\/Cas9 designs for targeting the HIV reservoir.","volume":"16","author":"P Roychoudhury","year":"2018","journal-title":"BMC Biol [Internet]."},{"issue":"5","key":"pcbi.1010003.ref007","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1056\/NEJMoa1108524","article-title":"Antiretroviral Prophylaxis for HIV Prevention in Heterosexual Men and Women","volume":"367","author":"JM Baeten","year":"2012","journal-title":"N Engl J Med [Internet]."},{"issue":"5","key":"pcbi.1010003.ref008","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1056\/NEJMoa1202614","article-title":"Preexposure Prophylaxis for HIV Infection among African Women","volume":"367","author":"L Van Damme","year":"2012","journal-title":"N Engl J Med [Internet]."},{"issue":"23","key":"pcbi.1010003.ref009","doi-asserted-by":"crossref","first-page":"2237","DOI":"10.1056\/NEJMoa1506273","article-title":"On-Demand Preexposure Prophylaxis in Men at High Risk for HIV-1 Infection","volume":"373","author":"J-M Molina","year":"2015","journal-title":"N Engl J Med 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