High monoclonal neutralization titers reduced breakthrough HIV-1 viral loads in the Antibody Mediated Prevention trials
Abstract The Antibody Mediated Prevention (AMP) trials (NCT02716675 and NCT02568215) demonstrated that passive administration of the broadly neutralizing monoclonal antibody VRC01 could prevent some HIV-1 acquisition events. Here, we use mathematical modeling in a post hoc analysis to demonstrate th...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2023-12-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-023-43384-y |
| _version_ | 1797247207272873984 |
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| author | Daniel B. Reeves Bryan T. Mayer Allan C. deCamp Yunda Huang Bo Zhang Lindsay N. Carpp Craig A. Magaret Michal Juraska Peter B. Gilbert David C. Montefiori Katharine J. Bar E. Fabian Cardozo-Ojeda Joshua T. Schiffer Raabya Rossenkhan Paul Edlefsen Lynn Morris Nonhlanhla N. Mkhize Carolyn Williamson James I. Mullins Kelly E. Seaton Georgia D. Tomaras Philip Andrew Nyaradzo Mgodi Julie E. Ledgerwood Myron S. Cohen Lawrence Corey Logashvari Naidoo Catherine Orrell Paul A. Goepfert Martin Casapia Magdalena E. Sobieszczyk Shelly T. Karuna Srilatha Edupuganti |
| author_facet | Daniel B. Reeves Bryan T. Mayer Allan C. deCamp Yunda Huang Bo Zhang Lindsay N. Carpp Craig A. Magaret Michal Juraska Peter B. Gilbert David C. Montefiori Katharine J. Bar E. Fabian Cardozo-Ojeda Joshua T. Schiffer Raabya Rossenkhan Paul Edlefsen Lynn Morris Nonhlanhla N. Mkhize Carolyn Williamson James I. Mullins Kelly E. Seaton Georgia D. Tomaras Philip Andrew Nyaradzo Mgodi Julie E. Ledgerwood Myron S. Cohen Lawrence Corey Logashvari Naidoo Catherine Orrell Paul A. Goepfert Martin Casapia Magdalena E. Sobieszczyk Shelly T. Karuna Srilatha Edupuganti |
| author_sort | Daniel B. Reeves |
| collection | DOAJ |
| description | Abstract The Antibody Mediated Prevention (AMP) trials (NCT02716675 and NCT02568215) demonstrated that passive administration of the broadly neutralizing monoclonal antibody VRC01 could prevent some HIV-1 acquisition events. Here, we use mathematical modeling in a post hoc analysis to demonstrate that VRC01 influenced viral loads in AMP participants who acquired HIV. Instantaneous inhibitory potential (IIP), which integrates VRC01 serum concentration and VRC01 sensitivity of acquired viruses in terms of both IC50 and IC80, follows a dose-response relationship with first positive viral load (p = 0.03), which is particularly strong above a threshold of IIP = 1.6 (r = -0.6, p = 2e-4). Mathematical modeling reveals that VRC01 activity predicted from in vitro IC80s and serum VRC01 concentrations overestimates in vivo neutralization by 600-fold (95% CI: 300–1200). The trained model projects that even if future therapeutic HIV trials of combination monoclonal antibodies do not always prevent acquisition, reductions in viremia and reservoir size could be expected. |
| first_indexed | 2024-03-08T22:37:25Z |
| format | Article |
| id | doaj.art-794805ba580c4e44895b377fd359c2eb |
| institution | Directory Open Access Journal |
| issn | 2041-1723 |
| language | English |
| last_indexed | 2024-04-24T19:55:01Z |
| publishDate | 2023-12-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj.art-794805ba580c4e44895b377fd359c2eb2024-03-24T12:24:47ZengNature PortfolioNature Communications2041-17232023-12-0114111510.1038/s41467-023-43384-yHigh monoclonal neutralization titers reduced breakthrough HIV-1 viral loads in the Antibody Mediated Prevention trialsDaniel B. Reeves0Bryan T. Mayer1Allan C. deCamp2Yunda Huang3Bo Zhang4Lindsay N. Carpp5Craig A. Magaret6Michal Juraska7Peter B. Gilbert8David C. Montefiori9Katharine J. Bar10E. Fabian Cardozo-Ojeda11Joshua T. Schiffer12Raabya Rossenkhan13Paul Edlefsen14Lynn Morris15Nonhlanhla N. Mkhize16Carolyn Williamson17James I. Mullins18Kelly E. Seaton19Georgia D. Tomaras20Philip Andrew21Nyaradzo Mgodi22Julie E. Ledgerwood23Myron S. Cohen24Lawrence Corey25Logashvari Naidoo26Catherine Orrell27Paul A. Goepfert28Martin Casapia29Magdalena E. Sobieszczyk30Shelly T. Karuna31Srilatha Edupuganti32Vaccine and Infectious Disease Division, Fred Hutchinson Cancer CenterVaccine and Infectious Disease Division, Fred Hutchinson Cancer CenterVaccine and Infectious Disease Division, Fred Hutchinson Cancer CenterVaccine and Infectious Disease Division, Fred Hutchinson Cancer CenterVaccine and Infectious Disease Division, Fred Hutchinson Cancer CenterVaccine and Infectious Disease Division, Fred Hutchinson Cancer CenterVaccine and Infectious Disease Division, Fred Hutchinson Cancer CenterVaccine and Infectious Disease Division, Fred Hutchinson Cancer CenterVaccine and Infectious Disease Division, Fred Hutchinson Cancer CenterDepartment of Surgery, Duke University Medical CenterPerelman School of Medicine, University of PennsylvaniaVaccine and Infectious Disease Division, Fred Hutchinson Cancer CenterVaccine and Infectious Disease Division, Fred Hutchinson Cancer CenterVaccine and Infectious Disease Division, Fred Hutchinson Cancer CenterVaccine and Infectious Disease Division, Fred Hutchinson Cancer CenterNational Institute for Communicable Diseases, National Health Laboratory ServiceNational Institute for Communicable Diseases, National Health Laboratory ServiceDivision of Medical Virology, Faculty of Health Sciences, University of Cape Town and National Health Laboratory ServiceDepartment of Global Health, University of WashingtonCenter for Human Systems Immunology, Duke UniversityCenter for Human Systems Immunology, Duke UniversityFamily Health InternationalClinical Trials Research Centre, University of Zimbabwe College of Health SciencesVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of HealthInstitute for Global Health and Infectious Diseases, The University of North Carolina at Chapel HillVaccine and Infectious Disease Division, Fred Hutchinson Cancer CenterSouth African Medical Research Council, HPRUDesmond Tutu HIV Centre, Institute of Infectious Disease and Molecular Medicine and Department of Medicine, University of Cape TownDivision of Infectious Diseases, Department of Medicine, University of Alabama at BirminghamFacultad de Medicina Humana, Universidad Nacional de la Amazonia PeruDivision of Infectious Diseases, Department of Medicine, Vagelos College of Physicians and Surgeons, New York-Presbyterian/Columbia University Irving Medical CenterVaccine and Infectious Disease Division, Fred Hutchinson Cancer CenterDivision of Infectious Diseases, Department of Medicine, Emory University School of MedicineAbstract The Antibody Mediated Prevention (AMP) trials (NCT02716675 and NCT02568215) demonstrated that passive administration of the broadly neutralizing monoclonal antibody VRC01 could prevent some HIV-1 acquisition events. Here, we use mathematical modeling in a post hoc analysis to demonstrate that VRC01 influenced viral loads in AMP participants who acquired HIV. Instantaneous inhibitory potential (IIP), which integrates VRC01 serum concentration and VRC01 sensitivity of acquired viruses in terms of both IC50 and IC80, follows a dose-response relationship with first positive viral load (p = 0.03), which is particularly strong above a threshold of IIP = 1.6 (r = -0.6, p = 2e-4). Mathematical modeling reveals that VRC01 activity predicted from in vitro IC80s and serum VRC01 concentrations overestimates in vivo neutralization by 600-fold (95% CI: 300–1200). The trained model projects that even if future therapeutic HIV trials of combination monoclonal antibodies do not always prevent acquisition, reductions in viremia and reservoir size could be expected.https://doi.org/10.1038/s41467-023-43384-y |
| spellingShingle | Daniel B. Reeves Bryan T. Mayer Allan C. deCamp Yunda Huang Bo Zhang Lindsay N. Carpp Craig A. Magaret Michal Juraska Peter B. Gilbert David C. Montefiori Katharine J. Bar E. Fabian Cardozo-Ojeda Joshua T. Schiffer Raabya Rossenkhan Paul Edlefsen Lynn Morris Nonhlanhla N. Mkhize Carolyn Williamson James I. Mullins Kelly E. Seaton Georgia D. Tomaras Philip Andrew Nyaradzo Mgodi Julie E. Ledgerwood Myron S. Cohen Lawrence Corey Logashvari Naidoo Catherine Orrell Paul A. Goepfert Martin Casapia Magdalena E. Sobieszczyk Shelly T. Karuna Srilatha Edupuganti High monoclonal neutralization titers reduced breakthrough HIV-1 viral loads in the Antibody Mediated Prevention trials Nature Communications |
| title | High monoclonal neutralization titers reduced breakthrough HIV-1 viral loads in the Antibody Mediated Prevention trials |
| title_full | High monoclonal neutralization titers reduced breakthrough HIV-1 viral loads in the Antibody Mediated Prevention trials |
| title_fullStr | High monoclonal neutralization titers reduced breakthrough HIV-1 viral loads in the Antibody Mediated Prevention trials |
| title_full_unstemmed | High monoclonal neutralization titers reduced breakthrough HIV-1 viral loads in the Antibody Mediated Prevention trials |
| title_short | High monoclonal neutralization titers reduced breakthrough HIV-1 viral loads in the Antibody Mediated Prevention trials |
| title_sort | high monoclonal neutralization titers reduced breakthrough hiv 1 viral loads in the antibody mediated prevention trials |
| url | https://doi.org/10.1038/s41467-023-43384-y |
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