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HIV-Specific T Cell Responses Are Highly Stable on Antiretroviral Therapy

HIV infection induces a robust T cell response that is sustained by high viremia, but falls following the onset of antiretroviral therapy (ART). Relatively little has been reported on the subsequent stability of the HIV-specific T cell response in individuals on durable therapy. Such data are critic...

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Autores principales: Xu, Yinyan, Trumble, Ilana M., Warren, Joanna A., Clutton, Genevieve, Abad-Fernandez, Maria, Kirchnerr, Jennifer, Adimora, Adaora A., Deeks, Steven G., Margolis, David M., Kuruc, JoAnn D., Gay, Cynthia L., Archin, Nancie M., Mollan, Katie R., Hudgens, Michael, Goonetilleke, Nilu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society of Gene & Cell Therapy 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6745511/
https://www.ncbi.nlm.nih.gov/pubmed/31534983
http://dx.doi.org/10.1016/j.omtm.2019.07.008
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author Xu, Yinyan
Trumble, Ilana M.
Warren, Joanna A.
Clutton, Genevieve
Abad-Fernandez, Maria
Kirchnerr, Jennifer
Adimora, Adaora A.
Deeks, Steven G.
Margolis, David M.
Kuruc, JoAnn D.
Gay, Cynthia L.
Archin, Nancie M.
Mollan, Katie R.
Hudgens, Michael
Goonetilleke, Nilu
author_facet Xu, Yinyan
Trumble, Ilana M.
Warren, Joanna A.
Clutton, Genevieve
Abad-Fernandez, Maria
Kirchnerr, Jennifer
Adimora, Adaora A.
Deeks, Steven G.
Margolis, David M.
Kuruc, JoAnn D.
Gay, Cynthia L.
Archin, Nancie M.
Mollan, Katie R.
Hudgens, Michael
Goonetilleke, Nilu
author_sort Xu, Yinyan
collection PubMed
description HIV infection induces a robust T cell response that is sustained by high viremia, but falls following the onset of antiretroviral therapy (ART). Relatively little has been reported on the subsequent stability of the HIV-specific T cell response in individuals on durable therapy. Such data are critical for powering clinical trials testing T cell-based immunotherapies. In a cross-sectional study, HIV-specific T cell responses were detectable by ex vivo interferon (IFN)-γ ELISpot (average ∼1,100 spot-forming units [SFUs]/10(6) peripheral blood mononuclear cells) in persons living with HIV (PLWH; n = 34), despite median durable ART suppression of 5.0 years. No substantial association was detected between the summed HIV-specific T cell response and the size of the replication-competent HIV reservoir. T cell responses were next measured in participants sampled weekly, monthly, or yearly. HIV-specific T cell responses were highly stable over the time periods examined; within-individual variation ranged from 16% coefficient of variation (CV) for weekly to 27% CV for yearly sampling. These data were used to generate power calculations for future immunotherapy studies. The stability of the HIV-specific T cell response in suppressed PLWH will enable powered studies of small sizes (e.g., n = 6–12), facilitating rapid and iterative testing for T cell-based immunotherapies against HIV.
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spelling pubmed-67455112019-09-18 HIV-Specific T Cell Responses Are Highly Stable on Antiretroviral Therapy Xu, Yinyan Trumble, Ilana M. Warren, Joanna A. Clutton, Genevieve Abad-Fernandez, Maria Kirchnerr, Jennifer Adimora, Adaora A. Deeks, Steven G. Margolis, David M. Kuruc, JoAnn D. Gay, Cynthia L. Archin, Nancie M. Mollan, Katie R. Hudgens, Michael Goonetilleke, Nilu Mol Ther Methods Clin Dev Article HIV infection induces a robust T cell response that is sustained by high viremia, but falls following the onset of antiretroviral therapy (ART). Relatively little has been reported on the subsequent stability of the HIV-specific T cell response in individuals on durable therapy. Such data are critical for powering clinical trials testing T cell-based immunotherapies. In a cross-sectional study, HIV-specific T cell responses were detectable by ex vivo interferon (IFN)-γ ELISpot (average ∼1,100 spot-forming units [SFUs]/10(6) peripheral blood mononuclear cells) in persons living with HIV (PLWH; n = 34), despite median durable ART suppression of 5.0 years. No substantial association was detected between the summed HIV-specific T cell response and the size of the replication-competent HIV reservoir. T cell responses were next measured in participants sampled weekly, monthly, or yearly. HIV-specific T cell responses were highly stable over the time periods examined; within-individual variation ranged from 16% coefficient of variation (CV) for weekly to 27% CV for yearly sampling. These data were used to generate power calculations for future immunotherapy studies. The stability of the HIV-specific T cell response in suppressed PLWH will enable powered studies of small sizes (e.g., n = 6–12), facilitating rapid and iterative testing for T cell-based immunotherapies against HIV. American Society of Gene & Cell Therapy 2019-08-14 /pmc/articles/PMC6745511/ /pubmed/31534983 http://dx.doi.org/10.1016/j.omtm.2019.07.008 Text en © 2019 The Authors http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Article
Xu, Yinyan
Trumble, Ilana M.
Warren, Joanna A.
Clutton, Genevieve
Abad-Fernandez, Maria
Kirchnerr, Jennifer
Adimora, Adaora A.
Deeks, Steven G.
Margolis, David M.
Kuruc, JoAnn D.
Gay, Cynthia L.
Archin, Nancie M.
Mollan, Katie R.
Hudgens, Michael
Goonetilleke, Nilu
HIV-Specific T Cell Responses Are Highly Stable on Antiretroviral Therapy
title HIV-Specific T Cell Responses Are Highly Stable on Antiretroviral Therapy
title_full HIV-Specific T Cell Responses Are Highly Stable on Antiretroviral Therapy
title_fullStr HIV-Specific T Cell Responses Are Highly Stable on Antiretroviral Therapy
title_full_unstemmed HIV-Specific T Cell Responses Are Highly Stable on Antiretroviral Therapy
title_short HIV-Specific T Cell Responses Are Highly Stable on Antiretroviral Therapy
title_sort hiv-specific t cell responses are highly stable on antiretroviral therapy
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6745511/
https://www.ncbi.nlm.nih.gov/pubmed/31534983
http://dx.doi.org/10.1016/j.omtm.2019.07.008
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