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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...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2022
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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. |
format | Online Article Text |
id | pubmed-9177424 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
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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