{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T14:59:01Z","timestamp":1788274741742,"version":"build-2803163510"},"reference-count":22,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2026,1,19]],"date-time":"2026-01-19T00:00:00Z","timestamp":1768780800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100017973","name":"International Maternal Pediatric Adolescent AIDS Clinical Trials Network","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100017973","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"}]},{"DOI":"10.13039\/100009633","name":"Eunice Kennedy Shriver National Institute of Child Health and Human Development","doi-asserted-by":"publisher","award":["HSN275201800001I"],"award-info":[{"award-number":["HSN275201800001I"]}],"id":[{"id":"10.13039\/100009633","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000025","name":"National Institute of Mental Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000025","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["UM1AI068632"],"award-info":[{"award-number":["UM1AI068632"]}],"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":["UM1AI068616"],"award-info":[{"award-number":["UM1AI068616"]}],"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":["UM1AI106716"],"award-info":[{"award-number":["UM1AI106716"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,1,19]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>To develop a population pharmacokinetic (popPK) model to understand factors affecting the broadly neutralizing HIV antibody (bNAb) VR07-523LS disposition and infant predicted serum neutralization 80% inhibitory dilution titre ratio (PT80) and its potential relationship to antiviral effects.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>PK data from two studies were used: infants exposed to HIV initiating therapy \u22645\u2005days of age (IMPAACT P1112, n\u200a=\u200a21) and healthy adults (VRC605, n\u200a=\u200a25). The infant study implemented fixed subcutaneous (s.c.) dosing whereas the adult study implemented weight-based dosing, via both intravenous (i.v.) and s.c. routes. Monte Carlo simulation assessed two doses (80\u2005mg followed by 100\u2005mg at 12\u2005weeks) to determine the maintenance of levels &amp;gt;10\u2005\u00b5g\/mL in virtual infants. The broadly neutralizing antibodies (bNAbs) concentration\/IC80 ratio (PT80) was calculated on the basis of simulated concentrations from the popPK model and VRC07-523LS HIV-1 sensitivity (IC80) distribution.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>This model predicts typical infant CL\/F and t1\/2 of 159\u2005mL\/day\/70\u2005kg and 39\u2005days. Comparatively, predicted adult typical CL\/F and t1\/2 were 269\u2005mL\/day\/70\u2005kg and 31\u2005days. Concentrations were &amp;gt;10\u2005\u00b5g\/mL in &amp;gt;87% of virtual infants at 12\u2005weeks following one dose and &amp;gt;98% at 24\u2005weeks following two doses. Median (90% predictive interval) PT80 was 163 (71\u2013383), 116 (51\u2013274) and 61 (26\u2013144) at 6, 8 and 12\u2005weeks, respectively. Significant model covariates included age (infant versus adult) and multiple dosing.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Age and repeat dosing influence VRC07-523LS PK. An 80-mg dose followed by 100\u2005mg at 12\u2005weeks rapidly achieves and maintains concentrations &amp;gt;10\u2005\u00b5g\/mL for &amp;gt;24\u2005weeks. This dosing strategy is expected to result in antiviral effects in patients with sensitive viruses and supports further evaluation of VRC07-523LS.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/jac\/dkaf449","type":"journal-article","created":{"date-parts":[[2025,12,2]],"date-time":"2025-12-02T12:55:24Z","timestamp":1764680124000},"source":"Crossref","is-referenced-by-count":2,"title":["Model-based assessment of VRC07-523LS dosing in infants through population pharmacokinetic -pharmacodynamic modelling in adults and infants"],"prefix":"10.1093","volume":"81","author":[{"given":"Dustin","family":"Huynh","sequence":"first","affiliation":[{"name":"Schools of Medicine and Skaggs School of Pharmacy, UC San Diego , La Jolla, CA 92093 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mina","family":"Nikanjam","sequence":"additional","affiliation":[{"name":"Schools of Medicine and Skaggs School of Pharmacy, UC San Diego , La Jolla, CA 92093 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Coleen K","family":"Cunningham","sequence":"additional","affiliation":[{"name":"School of Medicine, UC Irvine, Irvine CA and Children\u2019s Hospital of Orange County , Orange, CA 92868 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth J","family":"McFarland","sequence":"additional","affiliation":[{"name":"Pediatric Infectious Diseases, University of Colorado School of Medicine , Aurora, CO 80045 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Petronella","family":"Muresan","sequence":"additional","affiliation":[{"name":"Statistical and Data Management Center (SDMC), Frontier Science Foundation , Boston, MA 02115 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charlotte","family":"Perlowski","sequence":"additional","affiliation":[{"name":"FHI 360 , Durham, NC 27701 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8599-1004","authenticated-orcid":false,"given":"Dwight E","family":"Yin","sequence":"additional","affiliation":[{"name":"Division of AIDS, National Institute of Allergy and Infectious Diseases , Bethesda, MD 20892 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jack","family":"Moye","sequence":"additional","affiliation":[{"name":"Maternal and Pediatric Infectious Disease Branch Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) , Bethesda, MD 20892 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans","family":"Spiegel","sequence":"additional","affiliation":[{"name":"Kelly Government Solutions, Contractor to NIAID\/NIH\/HHS , Rockville, MD ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucio","family":"Gama","sequence":"additional","affiliation":[{"name":"Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health , Bethesda, MD 20892 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Gaudinski","sequence":"additional","affiliation":[{"name":"Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health , Bethesda, MD 20892 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edmund V","family":"Capparelli","sequence":"additional","affiliation":[{"name":"Schools of Medicine and Skaggs School of Pharmacy, UC San Diego , La Jolla, CA 92093 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