ResearchIn-Press PreviewAIDS/HIVImmunology
Open Access | 10.1172/jci.insight.142640
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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Thomas, A.
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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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Huang, S.
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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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Bui, J.
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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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Lee, G.
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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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Gramatica, A.
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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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Conce Alberto, W.
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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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McMahon, D.
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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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Eron, J.
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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
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.