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ResearchIn-Press PreviewAIDS/HIVImmunology Open Access | 10.1172/jci.insight.142640

HIV-specific T-cell responses reflect substantive in vivo interactions with antigen despite long-term therapy

Eva M. Stevenson,1 Adam R. Ward,2 Ronald Truong,2 Allison S. Thomas,3 Szu-Han Huang,2 Thomas R. Dilling,1 Sandra Terry,1 John K. Bui,1 Talia M. Mota,1 Ali Danesh,1 Guinevere Q. Lee,1 Andrea Gramatica,1 Pragya Khadka,1 Winiffer D. Conce Alberto,1 Rajesh T. Gandhi,5 Deborah K. McMahon,6 Christina M. Lalama,7 Ronald J. Bosch,7 Bernard J. Macatangay,6 Joshua C. Cyktor,6 Joseph J. Eron,8 John W. Mellors,6 and R. Brad Jones1

1Division of Infectious Diseases, Weill Cornell Medicine, New York, United States of America

2Department of Microbiology, Immunology, and Tropical Medicine, George Washington University, Washington, United States of America

3Department of Microbiology, Boston University School of Medicine, Boston, United States of America

4Division of Infectious Diseases, Weill Cornell Medicine, New York City, United States of America

5Division of Infectious Disease, Massachussetts General Hospital, Boston, United States of America

6Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, United States of America

7Center for Biostatistics in AIDS Research, Harvard T.H. Chan School of Public Health, Boston, United States of America

8Department of Medicine, UNC Chapel Hill, Chapel Hill, United States of America

Find articles by Stevenson, E. in: JCI | PubMed | Google Scholar

1Division of Infectious Diseases, Weill Cornell Medicine, New York, United States of America

2Department of Microbiology, Immunology, and Tropical Medicine, George Washington University, Washington, United States of America

3Department of Microbiology, Boston University School of Medicine, Boston, United States of America

4Division of Infectious Diseases, Weill Cornell Medicine, New York City, United States of America

5Division of Infectious Disease, Massachussetts General Hospital, Boston, United States of America

6Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, United States of America

7Center for Biostatistics in AIDS Research, Harvard T.H. Chan School of Public Health, Boston, United States of America

8Department of Medicine, UNC Chapel Hill, Chapel Hill, United States of America

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1Division of Infectious Diseases, Weill Cornell Medicine, New York, United States of America

2Department of Microbiology, Immunology, and Tropical Medicine, George Washington University, Washington, United States of America

3Department of Microbiology, Boston University School of Medicine, Boston, United States of America

4Division of Infectious Diseases, Weill Cornell Medicine, New York City, United States of America

5Division of Infectious Disease, Massachussetts General Hospital, Boston, United States of America

6Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, United States of America

7Center for Biostatistics in AIDS Research, Harvard T.H. Chan School of Public Health, Boston, United States of America

8Department of Medicine, UNC Chapel Hill, Chapel Hill, United States of America

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1Division of Infectious Diseases, Weill Cornell Medicine, New York, United States of America

2Department of Microbiology, Immunology, and Tropical Medicine, George Washington University, Washington, United States of America

3Department of Microbiology, Boston University School of Medicine, Boston, United States of America

4Division of Infectious Diseases, Weill Cornell Medicine, New York City, United States of America

5Division of Infectious Disease, Massachussetts General Hospital, Boston, United States of America

6Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, United States of America

7Center for Biostatistics in AIDS Research, Harvard T.H. Chan School of Public Health, Boston, United States of America

8Department of Medicine, UNC Chapel Hill, Chapel Hill, United States of America

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1Division of Infectious Diseases, Weill Cornell Medicine, New York, United States of America

2Department of Microbiology, Immunology, and Tropical Medicine, George Washington University, Washington, United States of America

3Department of Microbiology, Boston University School of Medicine, Boston, United States of America

4Division of Infectious Diseases, Weill Cornell Medicine, New York City, United States of America

5Division of Infectious Disease, Massachussetts General Hospital, Boston, United States of America

6Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, United States of America

7Center for Biostatistics in AIDS Research, Harvard T.H. Chan School of Public Health, Boston, United States of America

8Department of Medicine, UNC Chapel Hill, Chapel Hill, United States of America

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1Division of Infectious Diseases, Weill Cornell Medicine, New York, United States of America

2Department of Microbiology, Immunology, and Tropical Medicine, George Washington University, Washington, United States of America

3Department of Microbiology, Boston University School of Medicine, Boston, United States of America

4Division of Infectious Diseases, Weill Cornell Medicine, New York City, United States of America

5Division of Infectious Disease, Massachussetts General Hospital, Boston, United States of America

6Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, United States of America

7Center for Biostatistics in AIDS Research, Harvard T.H. Chan School of Public Health, Boston, United States of America

8Department of Medicine, UNC Chapel Hill, Chapel Hill, United States of America

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1Division of Infectious Diseases, Weill Cornell Medicine, New York, United States of America

2Department of Microbiology, Immunology, and Tropical Medicine, George Washington University, Washington, United States of America

3Department of Microbiology, Boston University School of Medicine, Boston, United States of America

4Division of Infectious Diseases, Weill Cornell Medicine, New York City, United States of America

5Division of Infectious Disease, Massachussetts General Hospital, Boston, United States of America

6Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, United States of America

7Center for Biostatistics in AIDS Research, Harvard T.H. Chan School of Public Health, Boston, United States of America

8Department of Medicine, UNC Chapel Hill, Chapel Hill, United States of America

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1Division of Infectious Diseases, Weill Cornell Medicine, New York, United States of America

2Department of Microbiology, Immunology, and Tropical Medicine, George Washington University, Washington, United States of America

3Department of Microbiology, Boston University School of Medicine, Boston, United States of America

4Division of Infectious Diseases, Weill Cornell Medicine, New York City, United States of America

5Division of Infectious Disease, Massachussetts General Hospital, Boston, United States of America

6Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, United States of America

7Center for Biostatistics in AIDS Research, Harvard T.H. Chan School of Public Health, Boston, United States of America

8Department of Medicine, UNC Chapel Hill, Chapel Hill, United States of America

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1Division of Infectious Diseases, Weill Cornell Medicine, New York, United States of America

2Department of Microbiology, Immunology, and Tropical Medicine, George Washington University, Washington, United States of America

3Department of Microbiology, Boston University School of Medicine, Boston, United States of America

4Division of Infectious Diseases, Weill Cornell Medicine, New York City, United States of America

5Division of Infectious Disease, Massachussetts General Hospital, Boston, United States of America

6Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, United States of America

7Center for Biostatistics in AIDS Research, Harvard T.H. Chan School of Public Health, Boston, United States of America

8Department of Medicine, UNC Chapel Hill, Chapel Hill, United States of America

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1Division of Infectious Diseases, Weill Cornell Medicine, New York, United States of America

2Department of Microbiology, Immunology, and Tropical Medicine, George Washington University, Washington, United States of America

3Department of Microbiology, Boston University School of Medicine, Boston, United States of America

4Division of Infectious Diseases, Weill Cornell Medicine, New York City, United States of America

5Division of Infectious Disease, Massachussetts General Hospital, Boston, United States of America

6Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, United States of America

7Center for Biostatistics in AIDS Research, Harvard T.H. Chan School of Public Health, Boston, United States of America

8Department of Medicine, UNC Chapel Hill, Chapel Hill, United States of America

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1Division of Infectious Diseases, Weill Cornell Medicine, New York, United States of America

2Department of Microbiology, Immunology, and Tropical Medicine, George Washington University, Washington, United States of America

3Department of Microbiology, Boston University School of Medicine, Boston, United States of America

4Division of Infectious Diseases, Weill Cornell Medicine, New York City, United States of America

5Division of Infectious Disease, Massachussetts General Hospital, Boston, United States of America

6Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, United States of America

7Center for Biostatistics in AIDS Research, Harvard T.H. Chan School of Public Health, Boston, United States of America

8Department of Medicine, UNC Chapel Hill, Chapel Hill, United States of America

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1Division of Infectious Diseases, Weill Cornell Medicine, New York, United States of America

2Department of Microbiology, Immunology, and Tropical Medicine, George Washington University, Washington, United States of America

3Department of Microbiology, Boston University School of Medicine, Boston, United States of America

4Division of Infectious Diseases, Weill Cornell Medicine, New York City, United States of America

5Division of Infectious Disease, Massachussetts General Hospital, Boston, United States of America

6Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, United States of America

7Center for Biostatistics in AIDS Research, Harvard T.H. Chan School of Public Health, Boston, United States of America

8Department of Medicine, UNC Chapel Hill, Chapel Hill, United States of America

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1Division of Infectious Diseases, Weill Cornell Medicine, New York, United States of America

2Department of Microbiology, Immunology, and Tropical Medicine, George Washington University, Washington, United States of America

3Department of Microbiology, Boston University School of Medicine, Boston, United States of America

4Division of Infectious Diseases, Weill Cornell Medicine, New York City, United States of America

5Division of Infectious Disease, Massachussetts General Hospital, Boston, United States of America

6Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, United States of America

7Center for Biostatistics in AIDS Research, Harvard T.H. Chan School of Public Health, Boston, United States of America

8Department of Medicine, UNC Chapel Hill, Chapel Hill, United States of America

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1Division of Infectious Diseases, Weill Cornell Medicine, New York, United States of America

2Department of Microbiology, Immunology, and Tropical Medicine, George Washington University, Washington, United States of America

3Department of Microbiology, Boston University School of Medicine, Boston, United States of America

4Division of Infectious Diseases, Weill Cornell Medicine, New York City, United States of America

5Division of Infectious Disease, Massachussetts General Hospital, Boston, United States of America

6Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, United States of America

7Center for Biostatistics in AIDS Research, Harvard T.H. Chan School of Public Health, Boston, United States of America

8Department of Medicine, UNC Chapel Hill, Chapel Hill, United States of America

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1Division of Infectious Diseases, Weill Cornell Medicine, New York, United States of America

2Department of Microbiology, Immunology, and Tropical Medicine, George Washington University, Washington, United States of America

3Department of Microbiology, Boston University School of Medicine, Boston, United States of America

4Division of Infectious Diseases, Weill Cornell Medicine, New York City, United States of America

5Division of Infectious Disease, Massachussetts General Hospital, Boston, United States of America

6Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, United States of America

7Center for Biostatistics in AIDS Research, Harvard T.H. Chan School of Public Health, Boston, United States of America

8Department of Medicine, UNC Chapel Hill, Chapel Hill, United States of America

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1Division of Infectious Diseases, Weill Cornell Medicine, New York, United States of America

2Department of Microbiology, Immunology, and Tropical Medicine, George Washington University, Washington, United States of America

3Department of Microbiology, Boston University School of Medicine, Boston, United States of America

4Division of Infectious Diseases, Weill Cornell Medicine, New York City, United States of America

5Division of Infectious Disease, Massachussetts General Hospital, Boston, United States of America

6Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, United States of America

7Center for Biostatistics in AIDS Research, Harvard T.H. Chan School of Public Health, Boston, United States of America

8Department of Medicine, UNC Chapel Hill, Chapel Hill, United States of America

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1Division of Infectious Diseases, Weill Cornell Medicine, New York, United States of America

2Department of Microbiology, Immunology, and Tropical Medicine, George Washington University, Washington, United States of America

3Department of Microbiology, Boston University School of Medicine, Boston, United States of America

4Division of Infectious Diseases, Weill Cornell Medicine, New York City, United States of America

5Division of Infectious Disease, Massachussetts General Hospital, Boston, United States of America

6Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, United States of America

7Center for Biostatistics in AIDS Research, Harvard T.H. Chan School of Public Health, Boston, United States of America

8Department of Medicine, UNC Chapel Hill, Chapel Hill, United States of America

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1Division of Infectious Diseases, Weill Cornell Medicine, New York, United States of America

2Department of Microbiology, Immunology, and Tropical Medicine, George Washington University, Washington, United States of America

3Department of Microbiology, Boston University School of Medicine, Boston, United States of America

4Division of Infectious Diseases, Weill Cornell Medicine, New York City, United States of America

5Division of Infectious Disease, Massachussetts General Hospital, Boston, United States of America

6Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, United States of America

7Center for Biostatistics in AIDS Research, Harvard T.H. Chan School of Public Health, Boston, United States of America

8Department of Medicine, UNC Chapel Hill, Chapel Hill, United States of America

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1Division of Infectious Diseases, Weill Cornell Medicine, New York, United States of America

2Department of Microbiology, Immunology, and Tropical Medicine, George Washington University, Washington, United States of America

3Department of Microbiology, Boston University School of Medicine, Boston, United States of America

4Division of Infectious Diseases, Weill Cornell Medicine, New York City, United States of America

5Division of Infectious Disease, Massachussetts General Hospital, Boston, United States of America

6Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, United States of America

7Center for Biostatistics in AIDS Research, Harvard T.H. Chan School of Public Health, Boston, United States of America

8Department of Medicine, UNC Chapel Hill, Chapel Hill, United States of America

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1Division of Infectious Diseases, Weill Cornell Medicine, New York, United States of America

2Department of Microbiology, Immunology, and Tropical Medicine, George Washington University, Washington, United States of America

3Department of Microbiology, Boston University School of Medicine, Boston, United States of America

4Division of Infectious Diseases, Weill Cornell Medicine, New York City, United States of America

5Division of Infectious Disease, Massachussetts General Hospital, Boston, United States of America

6Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, United States of America

7Center for Biostatistics in AIDS Research, Harvard T.H. Chan School of Public Health, Boston, United States of America

8Department of Medicine, UNC Chapel Hill, Chapel Hill, United States of America

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1Division of Infectious Diseases, Weill Cornell Medicine, New York, United States of America

2Department of Microbiology, Immunology, and Tropical Medicine, George Washington University, Washington, United States of America

3Department of Microbiology, Boston University School of Medicine, Boston, United States of America

4Division of Infectious Diseases, Weill Cornell Medicine, New York City, United States of America

5Division of Infectious Disease, Massachussetts General Hospital, Boston, United States of America

6Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, United States of America

7Center for Biostatistics in AIDS Research, Harvard T.H. Chan School of Public Health, Boston, United States of America

8Department of Medicine, UNC Chapel Hill, Chapel Hill, United States of America

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1Division of Infectious Diseases, Weill Cornell Medicine, New York, United States of America

2Department of Microbiology, Immunology, and Tropical Medicine, George Washington University, Washington, United States of America

3Department of Microbiology, Boston University School of Medicine, Boston, United States of America

4Division of Infectious Diseases, Weill Cornell Medicine, New York City, United States of America

5Division of Infectious Disease, Massachussetts General Hospital, Boston, United States of America

6Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, United States of America

7Center for Biostatistics in AIDS Research, Harvard T.H. Chan School of Public Health, Boston, United States of America

8Department of Medicine, UNC Chapel Hill, Chapel Hill, United States of America

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1Division of Infectious Diseases, Weill Cornell Medicine, New York, United States of America

2Department of Microbiology, Immunology, and Tropical Medicine, George Washington University, Washington, United States of America

3Department of Microbiology, Boston University School of Medicine, Boston, United States of America

4Division of Infectious Diseases, Weill Cornell Medicine, New York City, United States of America

5Division of Infectious Disease, Massachussetts General Hospital, Boston, United States of America

6Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, United States of America

7Center for Biostatistics in AIDS Research, Harvard T.H. Chan School of Public Health, Boston, United States of America

8Department of Medicine, UNC Chapel Hill, Chapel Hill, United States of America

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Published January 5, 2021 - More info

JCI Insight. https://doi.org/10.1172/jci.insight.142640.
Copyright © 2021, Stevenson et al. This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Published January 5, 2021 - Version history
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Abstract

Antiretroviral therapies (ART) abrogate HIV replication; however, infection persists as long-lived reservoirs of infected cells with integrated proviruses, which re-seed replication if ART is interrupted. A central tenet of our current understanding of this persistence is that infected cells are shielded from immune recognition and elimination through a lack of antigen expression from proviruses. Efforts to cure HIV infection have therefore focused on reactivating latent proviruses to enable immune-mediated clearance, but these have yet to succeed in reducing viral reservoirs. Here, we revisited the question of whether HIV reservoirs are predominately immunologically silent from a new angle: by querying the dynamics of HIV-specific T-cell responses over long-term ART for evidence of ongoing recognition of HIV-infected cells. In longitudinal assessments, we show that the rates of change in persisting HIV Nef-specific responses, but not responses to other HIV gene products, were associated with residual frequencies of infected cells. These Nef-specific responses were highly stable over time, and disproportionately exhibited a cytotoxic, effector functional profile, indicative of recent in vivo recognition of HIV antigens. These results indicate substantial visibility of the HIV-infected cells to T-cells on stable ART, presenting both opportunities and challenges for the development of therapeutic approaches to curing infection.

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