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@article{Fumagalli:2025:10.1101/2025.11.03.25339415,
author = {Fumagalli, MJ and Kaczynska, A and Allombert, M and Lopes-Ribeiro, Á and de, Oliveira Silva M and Hernandez, BJ and Lavine, C and Espinosa, SM and Brown, H and Box, H and Falaschetti, E and Cherrill, L-R and Elliott, T and Lee, M and Fox, J and Pett, S and Clarke, A and Uriel, A and Sogaard, O and Sutherland, R and Boffito, M and Kinloch-Loes, S and Orkin, C and Collins, S and Zacharopoulou, P and Robison, N and Bittar, C and Oliveira, T and Gazumyan, A and Jankovic, M and Seaman, MS and Frater, J and Caskey, M and Fidler, S and Nussenzweig, MC},
doi = {10.1101/2025.11.03.25339415},
journal = {medRxiv},
title = {Enhanced HIV-1 Control After Antibody Therapy is Associated with Autologous Antibodies and Reservoir Clearance in the RIO trial.},
url = {http://dx.doi.org/10.1101/2025.11.03.25339415},
year = {2025}
}
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TY  - JOUR
AB  - RIO is an ongoing double blind randomized placebo controlled human trial in which participants that started antiretroviral therapy (ART) during primary or early-stage infection underwent treatment interruption and were randomly assigned to a group receiving one or two doses of two long acting broadly neutralizing antibodies 3BNC117-LS and 10-1074-LS (Arm A), or saline (Arm B). The two arms differed significantly in time to viral rebound, ART restart and number of individuals that remained off therapy after 96 weeks (p=0.001) 1 . Here we report on the relationship between viremic control, the latent HIV-1 proviral reservoir, rebound viruses and their sensitivity to the infused and autologous antibodies. Pre-infusion reservoir measurements showed low levels of intact proviral HIV-1 DNA in circulating CD4+ T cells in both arms. The rebounding viruses in participants that received the antibodies, showed significant selection for resistance to 10-1074-LS but not to 3BNC117-LS. Notably, there was a significant correlation between initial reservoir sensitivity to autologous antibodies and to 10-1074 and time to rebound. Finally, comparison of pre-infusion and pre-rebound HIV-1 proviral reservoir in participants that received antibodies showed that the reservoir of intact proviruses decayed faster than earlier reports with a half-life of 0.65 years.
AU  - Fumagalli,MJ
AU  - Kaczynska,A
AU  - Allombert,M
AU  - Lopes-Ribeiro,Á
AU  - de,Oliveira Silva M
AU  - Hernandez,BJ
AU  - Lavine,C
AU  - Espinosa,SM
AU  - Brown,H
AU  - Box,H
AU  - Falaschetti,E
AU  - Cherrill,L-R
AU  - Elliott,T
AU  - Lee,M
AU  - Fox,J
AU  - Pett,S
AU  - Clarke,A
AU  - Uriel,A
AU  - Sogaard,O
AU  - Sutherland,R
AU  - Boffito,M
AU  - Kinloch-Loes,S
AU  - Orkin,C
AU  - Collins,S
AU  - Zacharopoulou,P
AU  - Robison,N
AU  - Bittar,C
AU  - Oliveira,T
AU  - Gazumyan,A
AU  - Jankovic,M
AU  - Seaman,MS
AU  - Frater,J
AU  - Caskey,M
AU  - Fidler,S
AU  - Nussenzweig,MC
DO  - 10.1101/2025.11.03.25339415
PY  - 2025///
TI  - Enhanced HIV-1 Control After Antibody Therapy is Associated with Autologous Antibodies and Reservoir Clearance in the RIO trial.
T2  - medRxiv
UR  - http://dx.doi.org/10.1101/2025.11.03.25339415
UR  - https://www.ncbi.nlm.nih.gov/pubmed/41282811
ER  -
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