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Combination therapy with broadly neutralizing antibodies, antiretroviral therapy and CCR5 blockade limits viral reservoir seeding in infant macaque model of HIV

delete2026-08-10
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OA
AI
J
Jonah B. Sacha *
T
Tracy Ordonez
S
Shilpi Pandey
G
Gabriela Webb
P
Philip Barnette
C
Cleiton Pessoa
M
Matthew Humkey
J
Jason Reed
A
Anden Morehead
J
Jennifer K. Watanabe
J
Jodie L. Usachenko
S
Shrivaas Vijayan
A
Altair Fazio
H
Heather Sidener
A
Anne D. Lewis
G
Gabrielle Pastenkos
S
Sohita Ojha
A
Aaron Barber-Axthelm
B
Bella Swan
R
Rachele Bochart
J
John R. Mascola
A
Amarendra Pegu
E
Emily J. Fray
R
Rachael M. Wolters
J
Janet D. Siliciano
R
Robert F. Siliciano
S
Scott G. Hansen
K
Koen K. A. Van Rompay
A
Ann J. Hessell
N
Nancy L. Haigwood *
DOI:10.1038/s41564-026-02444-xdelete
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Abstract

Abstract

En 中文
Lack of access to antiretroviral therapy (ART) leads to the transmission of human immunodeficiency virus in ~120,000 children annually, emphasizing the need for new strategies to prevent lifelong infection. Here in an infant rhesus macaque model of peripartum oral infection, we show that broadly neutralizing antibodies directed to the viral envelope protein were insufficient to prevent latent reservoir establishment, independent of daily ART. Blockade of the human immunodeficiency virus co-receptor CCR5 via the antibody leronlimab also failed to prevent reservoir establishment, but it significantly reduced reservoir seeding in lymphoid and gastrointestinal tissues. Following the treatment of infants with viraemia at 72 h post-infection with the combination of broadly neutralizing antibodies, ART and leronlimab, no subsequent evidence of replicating or latent virus and antiviral immunity was observed 1 year after treatment interruption. These findings suggest a synergy between broadly neutralizing antibodies, ART and CCR5 blockade for preventing viral reservoir establishment and offer potential improvements over current therapies for newborns exposed to human immunodeficiency virus. A combined therapy using broadly neutralizing antibodies that target the HIV envelope protein, the CCR5-blocking antibody leronlimab and antiretroviral therapy limits seeding of the viral reservoir in an infant macaque model of HIV at 72 h post-infection.

Journal

Nature Microbiology cover
Nature Microbiology
IF:
19.4
Papers:
576
Citations:
2.7W

Organization

N
national institutes of health
Scholars:
2.8K
Papers: 798
Citations: 0
O
Oregon Health & Science University
Scholars:
2.5W
Papers: 2.1W
Citations: 39
U
University of California
Scholars:
7.3K
Papers: 2.8K
Citations: 8.3W
T
the johns hopkins university school of medicine
Scholars:
41
Papers: 20
Citations: 0
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