Adults on pre-exposure prophylaxis (tenofovir-emtricitabine) have faster clearance of anti-HIV monoclonal antibody VRC01.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
28 Nov 2023
28 Nov 2023
Historique:
received:
01
06
2023
accepted:
08
11
2023
medline:
30
11
2023
pubmed:
29
11
2023
entrez:
28
11
2023
Statut:
epublish
Résumé
Broadly neutralizing monoclonal antibodies (mAbs) are being developed for HIV-1 prevention. Hence, these mAbs and licensed oral pre-exposure prophylaxis (PrEP) (tenofovir-emtricitabine) can be concomitantly administered in clinical trials. In 48 US participants (men and transgender persons who have sex with men) who received the HIV-1 mAb VRC01 and remained HIV-free in an antibody-mediated-prevention trial (ClinicalTrials.gov #NCT02716675), we conduct a post-hoc analysis and find that VRC01 clearance is 0.08 L/day faster (p = 0.005), and dose-normalized area-under-the-curve of VRC01 serum concentration over-time is 0.29 day/mL lower (p < 0.001) in PrEP users (n = 24) vs. non-PrEP users (n = 24). Consequently, PrEP users are predicted to have 14% lower VRC01 neutralization-mediated prevention efficacy against circulating HIV-1 strains. VRC01 clearance is positively associated (r = 0.33, p = 0.03) with levels of serum intestinal Fatty Acid Binding protein (I-FABP), a marker of epithelial intestinal permeability, which is elevated upon starting PrEP (p = 0.04) and after months of self-reported use (p = 0.001). These findings have implications for the evaluation of future HIV-1 mAbs and postulate a potential mechanism for mAb clearance in the context of PrEP.
Identifiants
pubmed: 38016958
doi: 10.1038/s41467-023-43399-5
pii: 10.1038/s41467-023-43399-5
pmc: PMC10684488
doi:
Substances chimiques
Tenofovir
99YXE507IL
Emtricitabine
G70B4ETF4S
VRC01 monoclonal antibody
0
Anti-HIV Agents
0
Antibodies, Monoclonal
0
Banques de données
ClinicalTrials.gov
['NCT02716675']
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
7813Subventions
Organisme : NIAID NIH HHS
ID : UM1 AI068613
Pays : United States
Organisme : NIAID NIH HHS
ID : UM1 AI068614
Pays : United States
Organisme : NIAID NIH HHS
ID : UM1 AI068618
Pays : United States
Organisme : NIAID NIH HHS
ID : UM1 AI068635
Pays : United States
Organisme : NIAID NIH HHS
ID : UM1 AI068619
Pays : United States
Organisme : NIAID NIH HHS
ID : UM1 AI068617
Pays : United States
Informations de copyright
© 2023. The Author(s).
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