ArticlebioRxiv : the preprint server for biology2024
Understanding early HIV-1 rebound dynamics following antiretroviral therapy interruption: The importance of effector cell expansion.
Tin Phan, Jessica M Conway, Nicole Pagane, Jasmine Kreig, Narmada Sambaturu, Sarafa Iyaniwura, Jonathan Z Li, Ruy M Ribeiro, Ruian Ke, Alan S Perelson
Abstract readPreprint
In one paragraphArticle in bioRxiv : the preprint server for biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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2 · The registryThe trial behind it
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5 · Who and what moneyAuthors and funding
10 authors.
Tin PhanTheoretical Biology and Biophysics, Los Alamos National Laboratory, Los Alamos, NM, USA.
Jessica M ConwayDepartment of Mathematics, Pennsylvania State University, College Township, PA, USA.
Nicole PaganeProgram in Computational and Systems Biology, Massachusetts Institute of Technology; Cambridge, MA, USA.
Jasmine KreigTheoretical Biology and Biophysics, Los Alamos National Laboratory, Los Alamos, NM, USA.
Narmada SambaturuTheoretical Biology and Biophysics, Los Alamos National Laboratory, Los Alamos, NM, USA.ORCID 0000-0002-2570-3699 Sarafa IyaniwuraTheoretical Biology and Biophysics, Los Alamos National Laboratory, Los Alamos, NM, USA.
Jonathan Z LiDepartment of Medicine, Division of Infectious Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Ruy M RibeiroTheoretical Biology and Biophysics, Los Alamos National Laboratory, Los Alamos, NM, USA.
Alan S PerelsonTheoretical Biology and Biophysics, Los Alamos National Laboratory, Los Alamos, NM, USA.ORCID 0000-0002-2455-0002 Funding
Leadership and Operations Center (LOC), AIDS Clinical Trials Group (ACTG); LOC 1/UM1AI068636 · NIAID · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Joseph J Eron, RAJESH T GANDHI · 2011 to 2026
$1073.1MStatistical and Data Management Center (SDMC), AIDS Clinical Trials Group (ACTG)UM1AI068634 · NIAID · HARVARD UNIVERSITY D/B/A HARVARD SCHOOL OF PUBLIC HEALTH · PI Marlene Ann Cooper, Michael David Hughes · 2011 to 2026
$246.6MAIDS Clinical Trials Group NetworkU01AI068636 · NIAID · SOCIAL AND SCIENTIFIC SYSTEMS, INC. · PI KURITZKES, DANIEL R. · 2006 to 2010
$147.1MValidation, CLIA and Qualification (VQC): Enhancing the RS ratio as a tool for AIDS Clinical Trial Group (ACTG) tuberculosis trialsUM1AI106701 · NIAID · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Grace M Aldrovandi · 2014 to 2026
$116.8MThe impact of HIV viral diversity and cellular immunity on HIV pathogenesisP30AI060354 · NIAID · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI ARTHUR Y KIM · 2004 to 2026
$94.4MStatistical and Data Management Center for the AIDS Clinical Trials GroupU01AI068634 · NIAID · HARVARD SCHOOL OF PUBLIC HEALTH · PI HUGHES, MICHAEL DAVID · 2006 to 2010
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$30.0MUnderstanding reservoir dynamics through analysis of viral decay processesP01AI169615 · NIAID · JOHNS HOPKINS UNIVERSITY · PI ROBERT F SILICIANO · 2022 to 2026
$9.5MHIV Reservoir Ecology of Viral Remission (PTC)R01AI150396 · NIAID · BRIGHAM AND WOMEN'S HOSPITAL · PI LI, JONATHAN · 2020 to 2025
$5.4MModeling Viral and T Lymphocyte DynamicsR01OD011095 · OD · TRIAD NATIONAL SECURITY, LLC · PI PERELSON, ALAN S · 2012 to 2024
$5.0MImmune System Modeling/HIVR01AI028433 · NIAID · UNIVERSITY OF CALIF-LOS ALAMOS NAT LAB · PI PERELSON, ALAN S · 1990 to 2021
$3.7MModeling the HIV latent reservoir, latency reversal and immunotherapeutics for HIV cureR01AI152703 · NIAID · TRIAD NATIONAL SECURITY, LLC · PI KE, RUIAN · 2020 to 2024
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6 · The paper itselfAbstract
Most people living with HIV-1 experience rapid viral rebound once antiretroviral therapy is interrupted; however, a small fraction remain in viral remission for an extended duration. Understanding the factors that determine whether viral rebound is likely after treatment interruption can enable the development of optimal treatment regimens and therapeutic interventions to potentially achieve a functional cure for HIV-1. We built upon the theoretical framework proposed by Conway and Perelson to construct dynamic models of virus-immune interactions to study factors that influence viral rebound dynamics. We evaluated these models using viral load data from 24 individuals following antiretroviral therapy interruption. The best-performing model accurately captures the heterogeneity of viral dynamics and highlights the importance of the effector cell expansion rate. Our results show that post-treatment controllers and non-controllers can be distinguished based on the effector cell expansion rate in our models. Furthermore, these results demonstrate the potential of using dynamic models incorporating an effector cell response to understand early viral rebound dynamics post-antiretroviral therapy interruption.
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PMID38746144
PMCPMC11092759
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