Evidence map›Paper›PMID 34106916›Full record

ArticlePLoS computational biology2021

Mechanistic basis of post-treatment control of SIV after anti-α4β7 antibody therapy.

Chad R Wells, Youfang Cao, David P Durham, Siddappa N Byrareddy, Aftab A Ansari, Nancy H Ruddle, Jeffrey P Townsend, Alison P Galvani, Alan S Perelson

Open access · goldAbstract read
In one paragraph

Article in PLoS computational biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
0.9field-weighted citation impact, top 31% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

7 citing papers in PubMed, 8 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Article
  6. Early treatment with anti-αFrontiers in immunology · 2022
    Article
  7. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors at 4 institutions in 1 country.

Chad R WellsCenter for Infectious Disease Modeling and Analysis, Yale School of Public Health, New Haven, Connecticut, United States of America.ORCID 0000-0003-1370-8350
Youfang CaoTheoretical Biology and Biophysics Group, Los Alamos National Laboratory, Los Alamos, New Mexico, United States of America.ORCID 0000-0002-5880-0006
David P DurhamCenter for Infectious Disease Modeling and Analysis, Yale School of Public Health, New Haven, Connecticut, United States of America.ORCID 0000-0002-4256-7705
Siddappa N ByrareddyDepartment of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, Nebraska, United States of America.ORCID 0000-0002-6889-4640
Aftab A AnsariDepartment of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, Georgia, United States of America.
Nancy H RuddleEpidemiology of Microbial Diseases, Yale School of Public Health, New Haven, Connecticut, United States of America.
Jeffrey P TownsendDepartment of Biostatistics, Yale University, New Haven, Connecticut, United States of America.ORCID 0000-0002-9890-3907
Alison P GalvaniCenter for Infectious Disease Modeling and Analysis, Yale School of Public Health, New Haven, Connecticut, United States of America.ORCID 0000-0002-2059-6716
Alan S PerelsonTheoretical Biology and Biophysics Group, Los Alamos National Laboratory, Los Alamos, New Mexico, United States of America.ORCID 0000-0002-2455-0002
Yale University · USLos Alamos National Laboratory · USEmory University · USUniversity of Nebraska Medical Center · US

Funding

Viral dynamics of rebound and control following early treatment of HIV/SIVP01AI131365 · NIAID · BOSTON COLLEGE · PI WHITNEY, JAMES BURTON · 2017 to 2021
$7.5M
Modeling Viral and T Lymphocyte DynamicsR01OD011095 · OD · TRIAD NATIONAL SECURITY, LLC · PI PERELSON, ALAN S · 2012 to 2024
$5.0M
Immune System Modeling/HIVR01AI028433 · NIAID · UNIVERSITY OF CALIF-LOS ALAMOS NAT LAB · PI PERELSON, ALAN S · 1990 to 2021
$3.7M
Limiting HIV establishment and maintenace by preserving intestinal immunityR01AI129745 · NIAID · UNIVERSITY OF NEBRASKA MEDICAL CENTER · PI BYRAREDDY, SIDDAPPA N, PAIARDINI, MIRKO · 2017 to 2020
$3.3M
NIAID NIH HHS P01 AI131365NIAID NIH HHS R01 AI028433NIAID NIH HHS R01 AI129745NIH HHS R01 OD011095
6 · The paper itself

Abstract

Treating macaques with an anti-α4β7 antibody under the umbrella of combination antiretroviral therapy (cART) during early SIV infection can lead to viral remission, with viral loads maintained at < 50 SIV RNA copies/ml after removal of all treatment in a subset of animals. Depletion of CD8+ lymphocytes in controllers resulted in transient recrudescence of viremia, suggesting that the combination of cART and anti-α4β7 antibody treatment led to a state where ongoing immune responses kept the virus undetectable in the absence of treatment. A previous mathematical model of HIV infection and cART incorporates immune effector cell responses and exhibits the property of two different viral load set-points. While the lower set-point could correspond to the attainment of long-term viral remission, attaining the higher set-point may be the result of viral rebound. Here we expand that model to include possible mechanisms of action of an anti-α4β7 antibody operating in these treated animals. We show that the model can fit the longitudinal viral load data from both IgG control and anti-α4β7 antibody treated macaques, suggesting explanations for the viral control associated with cART and an anti-α4β7 antibody treatment. This effective perturbation to the virus-host interaction can also explain observations in other nonhuman primate experiments in which cART and immunotherapy have led to post-treatment control or resetting of the viral load set-point. Interestingly, because the viral kinetics in the various treated animals differed-some animals exhibited large fluctuations in viral load after cART cessation-the model suggests that anti-α4β7 treatment could act by different primary mechanisms in different animals and still lead to post-treatment viral control. This outcome is nonetheless in accordance with a model with two stable viral load set-points, in which therapy can perturb the system from one set-point to a lower one through different biological mechanisms.

Indexed as

AnimalsAntibodies, MonoclonalAntiviral AgentsCD8-Positive T-LymphocytesCombined Modality TherapyIntegrinsLymphocyte DepletionMacacaSimian Acquired Immunodeficiency SyndromeSimian Immunodeficiency VirusViral LoadAntibodies, MonoclonalAntiviral Agentsintegrin alpha4beta7Integrins

Identifiers

PMID34106916
PMCPMC8189501
OpenAlexW3168702313

What Socratic holds

Textmetadata
LicenceCC0
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.