High monoclonal neutralization titers reduced breakthrough HIV-1 viral loads in the Antibody Mediated Prevention trials.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
14 Dec 2023
14 Dec 2023
Historique:
received:
13
06
2023
accepted:
07
11
2023
medline:
15
12
2023
pubmed:
15
12
2023
entrez:
14
12
2023
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 38097552
doi: 10.1038/s41467-023-43384-y
pii: 10.1038/s41467-023-43384-y
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
8299Subventions
Organisme : NIAID NIH HHS
ID : K25 AI155224
Pays : United States
Organisme : NIAID NIH HHS
ID : UM1 AI068635
Pays : United States
Organisme : NIAID NIH HHS
ID : UM1 AI068635
Pays : United States
Organisme : NIAID NIH HHS
ID : UM1 AI068614
Pays : United States
Organisme : NIAID NIH HHS
ID : P30 AI064518
Pays : United States
Organisme : NIAID NIH HHS
ID : UM1 AI068619
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI150500
Pays : United States
Informations de copyright
© 2023. The Author(s).
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