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Research LetterIn-Press PreviewAIDS/HIVInfectious diseaseVirology Open Access | 10.1172/JCI190824

Widespread distribution of transcriptionally active, clonally expanded, HIV-1 proviruses despite suppressive antiretroviral therapy

Hiromi Imamichi,1 Ven Natarajan,2 Francesca Scrimieri,2 Mindy Smith,1 Yunden Badralmaa,3 Marjorie Bosche,3 Jack M. Hensien,1 Thomas Buerkert,1 Weizhong Chang,3 Brad T. Sherman,3 Kanal Singh,1 and H. Clifford Lane1

1Clinical and Molecular Retrovirology Section, NIH, Bethesda, United States of America

2Clinical Services Program, Frederick National Laboratory for Cancer Research, Frederick, United States of America

3Frederick National Laboratory for Cancer Research, Frederick, United States of America

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1Clinical and Molecular Retrovirology Section, NIH, Bethesda, United States of America

2Clinical Services Program, Frederick National Laboratory for Cancer Research, Frederick, United States of America

3Frederick National Laboratory for Cancer Research, Frederick, United States of America

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1Clinical and Molecular Retrovirology Section, NIH, Bethesda, United States of America

2Clinical Services Program, Frederick National Laboratory for Cancer Research, Frederick, United States of America

3Frederick National Laboratory for Cancer Research, Frederick, United States of America

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1Clinical and Molecular Retrovirology Section, NIH, Bethesda, United States of America

2Clinical Services Program, Frederick National Laboratory for Cancer Research, Frederick, United States of America

3Frederick National Laboratory for Cancer Research, Frederick, United States of America

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1Clinical and Molecular Retrovirology Section, NIH, Bethesda, United States of America

2Clinical Services Program, Frederick National Laboratory for Cancer Research, Frederick, United States of America

3Frederick National Laboratory for Cancer Research, Frederick, United States of America

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1Clinical and Molecular Retrovirology Section, NIH, Bethesda, United States of America

2Clinical Services Program, Frederick National Laboratory for Cancer Research, Frederick, United States of America

3Frederick National Laboratory for Cancer Research, Frederick, United States of America

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1Clinical and Molecular Retrovirology Section, NIH, Bethesda, United States of America

2Clinical Services Program, Frederick National Laboratory for Cancer Research, Frederick, United States of America

3Frederick National Laboratory for Cancer Research, Frederick, United States of America

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1Clinical and Molecular Retrovirology Section, NIH, Bethesda, United States of America

2Clinical Services Program, Frederick National Laboratory for Cancer Research, Frederick, United States of America

3Frederick National Laboratory for Cancer Research, Frederick, United States of America

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1Clinical and Molecular Retrovirology Section, NIH, Bethesda, United States of America

2Clinical Services Program, Frederick National Laboratory for Cancer Research, Frederick, United States of America

3Frederick National Laboratory for Cancer Research, Frederick, United States of America

Find articles by Chang, W. in: PubMed | Google Scholar

1Clinical and Molecular Retrovirology Section, NIH, Bethesda, United States of America

2Clinical Services Program, Frederick National Laboratory for Cancer Research, Frederick, United States of America

3Frederick National Laboratory for Cancer Research, Frederick, United States of America

Find articles by Sherman, B. in: PubMed | Google Scholar

1Clinical and Molecular Retrovirology Section, NIH, Bethesda, United States of America

2Clinical Services Program, Frederick National Laboratory for Cancer Research, Frederick, United States of America

3Frederick National Laboratory for Cancer Research, Frederick, United States of America

Find articles by Singh, K. in: PubMed | Google Scholar |

1Clinical and Molecular Retrovirology Section, NIH, Bethesda, United States of America

2Clinical Services Program, Frederick National Laboratory for Cancer Research, Frederick, United States of America

3Frederick National Laboratory for Cancer Research, Frederick, United States of America

Find articles by Lane, H. in: PubMed | Google Scholar |

Published April 29, 2025 - More info

J Clin Invest. https://doi.org/10.1172/JCI190824.
Copyright © 2025, Imamichi 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 April 29, 2025 - Version history
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Abstract

The rapid viral rebound observed following treatment interruption, despite prolonged time on antiretroviral therapy with plasma HIV-RNA levels <40 copies/mL, suggests persistent HIV-1 reservoir(s) outside of the blood. Studies of HIV-1 proviruses in autopsy tissue samples have hinted at their persistence. However, their distribution across different anatomical compartments and their transcriptional activity within tissues remains unclear. The present study has examined molecular DNA and RNA reservoirs of HIV-1 in autopsy samples from 13 individuals with HIV-1 infection. Of the 13, 5 had detectable levels of HIV-1 RNA in plasma while 8 did not. Cell associated HIV-RNA was detected in 12 out of 13 donors and in 27 of the 30 different tissues examined. HIV-specific DNA and RNA were widely distributed and predominantly associated with clonal expansions. No significant differences were noted between the groups and no tissues were preferentially affected. These data imply that a substantial seeding of tissues with cells harboring transcriptionally active proviral DNA can be seen in the setting of HIV-1 infection despite ART and highlight one of the challenges in achieving an HIV-1 cure.

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