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Prolonged viral suppression with anti-HIV-1 antibody therapy

HIV-1 infection remains a public health problem with no cure. Anti-retroviral therapy (ART) is effective but requires lifelong drug administration owing to a stable reservoir of latent proviruses integrated into the genome of CD4(+) T cells(1). Immunotherapy with anti-HIV-1 antibodies has the potent...

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Autores principales: Gaebler, Christian, Nogueira, Lilian, Stoffel, Elina, Oliveira, Thiago Y., Breton, Gaëlle, Millard, Katrina G., Turroja, Martina, Butler, Allison, Ramos, Victor, Seaman, Michael S., Reeves, Jacqueline D., Petroupoulos, Christos J., Shimeliovich, Irina, Gazumyan, Anna, Jiang, Caroline S., Jilg, Nikolaus, Scheid, Johannes F., Gandhi, Rajesh, Walker, Bruce D., Sneller, Michael C., Fauci, Anthony, Chun, Tae-Wook, Caskey, Marina, Nussenzweig, Michel C.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9177424/
https://www.ncbi.nlm.nih.gov/pubmed/35418681
http://dx.doi.org/10.1038/s41586-022-04597-1
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author Gaebler, Christian
Nogueira, Lilian
Stoffel, Elina
Oliveira, Thiago Y.
Breton, Gaëlle
Millard, Katrina G.
Turroja, Martina
Butler, Allison
Ramos, Victor
Seaman, Michael S.
Reeves, Jacqueline D.
Petroupoulos, Christos J.
Shimeliovich, Irina
Gazumyan, Anna
Jiang, Caroline S.
Jilg, Nikolaus
Scheid, Johannes F.
Gandhi, Rajesh
Walker, Bruce D.
Sneller, Michael C.
Fauci, Anthony
Chun, Tae-Wook
Caskey, Marina
Nussenzweig, Michel C.
author_facet Gaebler, Christian
Nogueira, Lilian
Stoffel, Elina
Oliveira, Thiago Y.
Breton, Gaëlle
Millard, Katrina G.
Turroja, Martina
Butler, Allison
Ramos, Victor
Seaman, Michael S.
Reeves, Jacqueline D.
Petroupoulos, Christos J.
Shimeliovich, Irina
Gazumyan, Anna
Jiang, Caroline S.
Jilg, Nikolaus
Scheid, Johannes F.
Gandhi, Rajesh
Walker, Bruce D.
Sneller, Michael C.
Fauci, Anthony
Chun, Tae-Wook
Caskey, Marina
Nussenzweig, Michel C.
author_sort Gaebler, Christian
collection PubMed
description HIV-1 infection remains a public health problem with no cure. Anti-retroviral therapy (ART) is effective but requires lifelong drug administration owing to a stable reservoir of latent proviruses integrated into the genome of CD4(+) T cells(1). Immunotherapy with anti-HIV-1 antibodies has the potential to suppress infection and increase the rate of clearance of infected cells(2,3). Here we report on a clinical study in which people living with HIV received seven doses of a combination of two broadly neutralizing antibodies over 20 weeks in the presence or absence of ART. Without pre-screening for antibody sensitivity, 76% (13 out of 17) of the volunteers maintained virologic suppression for at least 20 weeks off ART. Post hoc sensitivity analyses were not predictive of the time to viral rebound. Individuals in whom virus remained suppressed for more than 20 weeks showed rebound viraemia after one of the antibodies reached serum concentrations below 10 µg ml(−1). Two of the individuals who received all seven antibody doses maintained suppression after one year. Reservoir analysis performed after six months of antibody therapy revealed changes in the size and composition of the intact proviral reservoir. By contrast, there was no measurable decrease in the defective reservoir in the same individuals. These data suggest that antibody administration affects the HIV-1 reservoir, but additional larger and longer studies will be required to define the precise effect of antibody immunotherapy on the reservoir.
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spelling pubmed-91774242022-06-10 Prolonged viral suppression with anti-HIV-1 antibody therapy Gaebler, Christian Nogueira, Lilian Stoffel, Elina Oliveira, Thiago Y. Breton, Gaëlle Millard, Katrina G. Turroja, Martina Butler, Allison Ramos, Victor Seaman, Michael S. Reeves, Jacqueline D. Petroupoulos, Christos J. Shimeliovich, Irina Gazumyan, Anna Jiang, Caroline S. Jilg, Nikolaus Scheid, Johannes F. Gandhi, Rajesh Walker, Bruce D. Sneller, Michael C. Fauci, Anthony Chun, Tae-Wook Caskey, Marina Nussenzweig, Michel C. Nature Article HIV-1 infection remains a public health problem with no cure. Anti-retroviral therapy (ART) is effective but requires lifelong drug administration owing to a stable reservoir of latent proviruses integrated into the genome of CD4(+) T cells(1). Immunotherapy with anti-HIV-1 antibodies has the potential to suppress infection and increase the rate of clearance of infected cells(2,3). Here we report on a clinical study in which people living with HIV received seven doses of a combination of two broadly neutralizing antibodies over 20 weeks in the presence or absence of ART. Without pre-screening for antibody sensitivity, 76% (13 out of 17) of the volunteers maintained virologic suppression for at least 20 weeks off ART. Post hoc sensitivity analyses were not predictive of the time to viral rebound. Individuals in whom virus remained suppressed for more than 20 weeks showed rebound viraemia after one of the antibodies reached serum concentrations below 10 µg ml(−1). Two of the individuals who received all seven antibody doses maintained suppression after one year. Reservoir analysis performed after six months of antibody therapy revealed changes in the size and composition of the intact proviral reservoir. By contrast, there was no measurable decrease in the defective reservoir in the same individuals. These data suggest that antibody administration affects the HIV-1 reservoir, but additional larger and longer studies will be required to define the precise effect of antibody immunotherapy on the reservoir. Nature Publishing Group UK 2022-04-13 2022 /pmc/articles/PMC9177424/ /pubmed/35418681 http://dx.doi.org/10.1038/s41586-022-04597-1 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Gaebler, Christian
Nogueira, Lilian
Stoffel, Elina
Oliveira, Thiago Y.
Breton, Gaëlle
Millard, Katrina G.
Turroja, Martina
Butler, Allison
Ramos, Victor
Seaman, Michael S.
Reeves, Jacqueline D.
Petroupoulos, Christos J.
Shimeliovich, Irina
Gazumyan, Anna
Jiang, Caroline S.
Jilg, Nikolaus
Scheid, Johannes F.
Gandhi, Rajesh
Walker, Bruce D.
Sneller, Michael C.
Fauci, Anthony
Chun, Tae-Wook
Caskey, Marina
Nussenzweig, Michel C.
Prolonged viral suppression with anti-HIV-1 antibody therapy
title Prolonged viral suppression with anti-HIV-1 antibody therapy
title_full Prolonged viral suppression with anti-HIV-1 antibody therapy
title_fullStr Prolonged viral suppression with anti-HIV-1 antibody therapy
title_full_unstemmed Prolonged viral suppression with anti-HIV-1 antibody therapy
title_short Prolonged viral suppression with anti-HIV-1 antibody therapy
title_sort prolonged viral suppression with anti-hiv-1 antibody therapy
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9177424/
https://www.ncbi.nlm.nih.gov/pubmed/35418681
http://dx.doi.org/10.1038/s41586-022-04597-1
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