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Author Notes:

Ann Chahroudi, 1760 Haygood Dr NE, Atlanta, Georgia 30322, USA. Phone: 404.727.9209; Email: achahro@emory.edu

VOP wrote the manuscript, conducted experiments, curated data, and performed analysis with supervision from AC. VOP, KMB, GM, FU, LR, DV, YD, and SL conducted experiments. AK led SGA studies and analysis, with coordination and input from SJB. Supervision of virologic assays and ImmunoPET scans were done by THV and PJS, respectively. SJ, JSW, FCCS, and SE coordinated animal support and care. KJB and GMS provided resources. AC, GGF, SRP, and GS conceptualized studies and acquired funding. All authors contributed to data interpretation and manuscript editing.

We would like to thank the YNPRC research resources team and the Center for Systems Imaging Core at Emory University for their contributions to this project.

The authors have declared that no conflict of interest exists.

Subjects:

Research Funding:

This work was funded by the US NIH (P01 AI131276, T32 AI074492, with additional support from UM1 AI164566). We also acknowledge contributions from the YNPRC (P51 OD011132) and the Translational Virology and Reservoir Cores of the Center for AIDS Research at Emory University (P30 AI050409).

Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Medicine, Research & Experimental
  • Research & Experimental Medicine
  • ANTIRETROVIRAL THERAPY
  • HIV-INFECTION
  • PROGRESSION
  • MUTATIONS
  • EMERGENCE
  • RESERVOIR
  • REVEALS
  • ESCAPE
  • BURDEN
  • MODELS

Dynamics and origin of rebound viremia in SHIV-infected infant macaques following interruption of long-term ART

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Journal Title:

JCI INSIGHT

Volume:

Volume 6, Number 23

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Type of Work:

Article | Final Publisher PDF

Abstract:

Understanding viral rebound in pediatric HIV-1 infection may inform the development of alternatives to lifelong antiretroviral therapy (ART) to achieve viral remission. We thus investigated viral rebound after analytical treatment interruption (ATI) in 10 infant macaques orally infected with SHIV.C.CH505 and treated with long-term ART. Rebound viremia was detected within 7 to 35 days of ATI in 9 of 10 animals, with posttreatment control of viremia seen in 5 of 5 Mamu-A*01+ macaques. Single-genome sequencing revealed that initial rebound virus was similar to viral DNA present in CD4+ T cells from blood, rectum, and lymph nodes before ATI. We assessed the earliest sites of viral reactivation immediately following ATI using ImmunoPET imaging. The largest increase in signal that preceded detectable viral RNA in plasma was found in the gastrointestinal (GI) tract, a site with relatively high SHIV RNA/DNA ratios in CD4+ T cells before ATI. Thus, the GI tract may be an initial source of rebound virus, but as ATI progresses, viral reactivation in other tissues likely contributes to the composition of plasma virus. Our study provides potentially novel insight into the features of viral rebound in pediatric infection and highlights the application of a noninvasive technique to monitor areas of HIV-1 expression in children.

Copyright information:

© 2021 Obregon-Perko et al.

This is an Open Access work distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/rdf).
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