{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,19]],"date-time":"2026-07-19T00:41:28Z","timestamp":1784421688114,"version":"3.55.0"},"reference-count":42,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2025,6,8]],"date-time":"2025-06-08T00:00:00Z","timestamp":1749340800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"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 AI068618"],"award-info":[{"award-number":["UM1 AI068618"]}],"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"}]}],"content-domain":{"domain":["accp1.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Clinical Pharma"],"published-print":{"date-parts":[[2025,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>VRC01 and VRC01LS are a pair of parental and LS\u2010modified anti\u2010HIV IgG1\u2010backboned monoclonal antibodies. In a Phase 1 clinical trial HVTN 116, 79 participants without HIV received intravenously one dose of VRC01 (30 mg\/kg, n = 16) or VRC01LS (30 mg\/kg, n = 10), four doses of VRC01 (10 mg\/kg, n = 23 or 30 mg\/kg, n = 23) every 2 months, or three doses of VRC01LS (30 mg\/kg, n = 7) every 3 months. Participants were followed for 6 (VRC01) or 12 (VRC01LS) months after the last dose. Using nonlinear mixed\u2010effects models, we conducted the first population pharmacokinetics analysis of VRC01\/LS concentrations in serum and rectal tissue, a primary site of HIV transmission. Serum concentration was described as a one\u2010compartment model in equilibrium with one tissue compartment, with first\u2010order elimination in both compartments. The model was parameterized with micro\u2010constants to estimate volumes of distribution for serum and tissue, serum\u2013tissue distribution rates (K12, K21), and elimination rate constants; distribution and elimination half\u2010life estimates were derived from the governing differential equations. To account for rectal biopsy heterogenicity between individuals, three normalization approaches were used: tissue weight adjusted, IgG concentration adjusted, and protein concentration adjusted. All three approaches rendered consistent estimates. Based on protein\u2010concentration\u2010normalized data, VRC01LS (vs VRC01) exhibited \u223c10\u2010fold higher concentrations over time in blood and rectal tissues, and faster blood\u2010to\u2010tissue distribution (K12 = 0.61 vs 0.13\/day). Median elimination half\u2010life estimates were 20 days for VRC01 and 63 days for VRC01LS in serum and rectal tissues. These data support lower dosage and\/or less frequent dosing of LS monoclonal antibodies providing potentially more immediate protection against HIV exposure in the rectum.<\/jats:p>","DOI":"10.1002\/jcph.70060","type":"journal-article","created":{"date-parts":[[2025,6,9]],"date-time":"2025-06-09T01:14:36Z","timestamp":1749431676000},"page":"1506-1516","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Pharmacokinetics Analysis of Serum and Rectal Tissue Concentrations of a Pair of Anti\u2010HIV Monoclonal Antibodies, VRC01 and VRC01LS, in Adults Without HIV"],"prefix":"10.1002","volume":"65","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1546-6172","authenticated-orcid":false,"given":"Yunda","family":"Huang","sequence":"first","affiliation":[{"name":"Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center Seattle WA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lily","family":"Zhang","sequence":"additional","affiliation":[{"name":"Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center Seattle WA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria P.","family":"Lemos","sequence":"additional","affiliation":[{"name":"Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center Seattle WA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rena D.","family":"Astronomo","sequence":"additional","affiliation":[{"name":"Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center Seattle WA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandeep","family":"Narpala","sequence":"additional","affiliation":[{"name":"Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health Bethesda MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madhu","family":"Prabhakaran","sequence":"additional","affiliation":[{"name":"Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health Bethesda MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nina Marie G.","family":"Garcia","sequence":"additional","affiliation":[{"name":"Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center Seattle WA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiwen","family":"Lu","sequence":"additional","affiliation":[{"name":"Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center Seattle WA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Greg J.","family":"Mize","sequence":"additional","affiliation":[{"name":"Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center Seattle WA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hayley","family":"Glantz","sequence":"additional","affiliation":[{"name":"Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center Seattle WA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hunter","family":"Colegrove","sequence":"additional","affiliation":[{"name":"Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center Seattle WA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philipp","family":"Mann","sequence":"additional","affiliation":[{"name":"Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center Seattle WA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmen A.","family":"Paez","sequence":"additional","affiliation":[{"name":"Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center Seattle WA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erica","family":"Andersen\u2010Nissen","sequence":"additional","affiliation":[{"name":"Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center Seattle WA USA"},{"name":"Cape Town HVTN Immunology Laboratory Hutchinson Centre Research Institute of South Africa Cape Town South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"Hutter","sequence":"additional","affiliation":[{"name":"Division of AIDS, National Institute of Allergy and Infectious Diseases, National Institutes of Health Bethesda MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie","family":"Dumond","sequence":"additional","affiliation":[{"name":"Division of Pharmacotherapy and Experimental Therapeutics University of North Carolina at Chapel Hill Chapel Hill NC USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adrian B.","family":"McDermott","sequence":"additional","affiliation":[{"name":"Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health Bethesda MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John R.","family":"Mascola","sequence":"additional","affiliation":[{"name":"Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health Bethesda MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard A.","family":"Koup","sequence":"additional","affiliation":[{"name":"Immunology Laboratory Vaccine Research Center National Institute for Allergy and Infectious Diseases, National Institutes of Health Bethesda MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linda\u2010Gail","family":"Bekker","sequence":"additional","affiliation":[{"name":"Desmond Tutu HIV Centre, University of Cape Town Cape Town South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. Juliana","family":"McElrath","sequence":"additional","affiliation":[{"name":"Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center Seattle WA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,6,8]]},"reference":[{"key":"e_1_2_11_2_1","unstructured":"UNAIDS.Fact sheet \u2010 latest global and regional statistics on the status of the AIDS epidemic.2023. Accessed January 17 2024.https:\/\/www.unaids.org\/en\/resources\/documents\/2024\/UNAIDS_FactSheet"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1011205"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(20)31065-5"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1097\/QAD.0000000000001145"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(22)00538-4"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2101016"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2031738"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2031499"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1310566"},{"key":"e_1_2_11_11_1","doi-asserted-by":"crossref","unstructured":"Johnson & Johnson. Johnson & Johnson and Global Partners Announce Results from Phase 2b Imbokodo HIV Vaccine Clinical Trial in Young Women in Sub\u2010Saharan Africa.2021. Accessed March 3 2023.https:\/\/www.jnj.com\/johnson\u2010johnson\u2010and\u2010global\u2010partners\u2010announce\u2010results\u2010from\u2010phase\u20102b\u2010imbokodo\u2010hiv\u2010vaccine\u2010clinical\u2010trial\u2010in\u2010young\u2010women\u2010in\u2010sub\u2010saharan\u2010africa","DOI":"10.5040\/9798216183723.ch-005"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.smim.2021.101475"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2352-3018(23)00264-3"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1187659"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1192819"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-022-01953-6"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2023.104590"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature13612"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri2155"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1403014"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.3390\/pharmaceutics16050594"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-54580-9"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jim.2021.112995"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btt456"},{"issue":"9","key":"e_1_2_11_25_1","first-page":"1524","article-title":"A new rectal model for dosimetry applications","volume":"40","author":"Mardirossian G","year":"1999","journal-title":"J Nucl Med."},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3003174"},{"key":"e_1_2_11_27_1","volume-title":"Monolix version 2021 R2","author":"Lixoft","year":"2021"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1214\/aos\/1018031103"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2020.103203"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1080\/19420862.2017.1311435"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1097\/00002030-199802000-00003"},{"issue":"4","key":"e_1_2_11_32_1","first-page":"823","article-title":"Detection, localization, and quantitation of HIV\u2010associated antigens in intestinal biopsies from patients with HIV","volume":"139","author":"Kotler DP","year":"1991","journal-title":"Am J Pathol."},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1086\/314628"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI27821"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1003776"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiu300"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200809122"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-022-01953-6"},{"key":"e_1_2_11_39_1","doi-asserted-by":"publisher","DOI":"10.1002\/sim.8310"},{"key":"e_1_2_11_40_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10928-013-9332-2"},{"key":"e_1_2_11_41_1","doi-asserted-by":"publisher","DOI":"10.1002\/psp4.12224"},{"key":"e_1_2_11_42_1","doi-asserted-by":"publisher","DOI":"10.1002\/jia2.26257"},{"key":"e_1_2_11_43_1","doi-asserted-by":"publisher","DOI":"10.1002\/bdd.1997"}],"container-title":["The Journal of Clinical Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcph.70060","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,1]],"date-time":"2025-11-01T07:43:07Z","timestamp":1761982987000},"score":1,"resource":{"primary":{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/10.1002\/jcph.70060"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6,8]]},"references-count":42,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2025,11]]}},"alternative-id":["10.1002\/jcph.70060"],"URL":"https:\/\/doi.org\/10.1002\/jcph.70060","archive":["Portico"],"relation":{},"ISSN":["0091-2700","1552-4604"],"issn-type":[{"value":"0091-2700","type":"print"},{"value":"1552-4604","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,6,8]]},"assertion":[{"value":"2025-04-16","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-05-22","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-06-08","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}