Evidence map›Paper›PMID 38964130›Full record

ArticleEpidemics2024

Assessing the impact of autologous virus neutralizing antibodies on viral rebound time in postnatally SHIV-infected ART-treated infant rhesus macaques.

Ellie Mainou, Stella J Berendam, Veronica Obregon-Perko, Emilie A Uffman, Caroline T Phan, George M Shaw, Katharine J Bar, Mithra R Kumar, Emily J Fray, Janet M Siliciano and 8 more

Abstract read
In one paragraph

Article in Epidemics, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
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

3 citing papers in PubMed.

  1. Article
  2. Article
  3. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

18 authors.

Ellie MainouDepartment of Biology, Pennsylvania State University, University Park, PA, USA. Electronic address: ejm6007@psu.edu.
Stella J BerendamGlaxoKlineSmith, Rockville, MD, USA.
Veronica Obregon-PerkoDepartment of Pediatrics, Emory University School of Medicine, Atlanta, GA 30322, USA.
Emilie A UffmanDuke Human Vaccine Institute, Duke University Medical Center, Durham, NC, USA.
Caroline T PhanDuke Human Vaccine Institute, Duke University Medical Center, Durham, NC, USA.
George M ShawPerelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Katharine J BarPerelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Mithra R KumarDepartment of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Emily J FrayDepartment of Biochemistry and Molecular Biology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Janet M SilicianoDepartment of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Robert F SilicianoDepartment of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Guido SilvestriYerkes National Primate Research Center, Emory University, Atlanta, GA, USA.
Sallie R PermarDepartment of Pediatrics, Weill Cornell Medicine, New York, NY, USA.
Genevieve G FoudaDepartment of Pediatrics, Weill Cornell Medicine, New York, NY, USA.
Janice McCarthyDepartment of Biostatistics and Bioinformatics, Duke University Medical Center, Durham, NC, USA.
Ann ChahroudiDepartment of Pediatrics, Emory University School of Medicine, Atlanta, GA 30322, USA.
Jessica M ConwayDepartment of Mathematics, Pennsylvania State University, University Park, PA, USA.
Cliburn ChanDepartment of Biostatistics and Bioinformatics, Duke University Medical Center, Durham, NC, USA.

Funding

Yerkes National Primate Research Center Role of type-I IFN in regulating COVID-19 induced inflammation and pathogenesisP51OD011132 · OD · EMORY UNIVERSITY · PI Joon Sup Lee · 2012 to 2026
$167.0M
Social and Behavioral Sciences CoreP30AI064518 · NIAID · DUKE UNIVERSITY · PI Nwora Lance Okeke · 2005 to 2026
$50.5M
Viral Testing Core-Maintenance of the SPF Breeding Colonies at Yerkes National Primate Research CenterU42OD011023 · OD · EMORY UNIVERSITY · PI Matthew Ryan Gardner · 2018 to 2026
$17.5M
Complementing broadly neutralizing antibodies and autologous responses to restrict virus escape and durably suppress HIV-1U01AI169767 · NIAID · UNIVERSITY OF PENNSYLVANIA · PI Katharine June Bar, Rebecca Marie Lynch · 2022 to 2026
$8.4M
The origin, predictors, and immune correlates of viral rebound in orally SHIV infected infant monkeysP01AI131276 · NIAID · WEILL MEDICAL COLL OF CORNELL UNIV · PI FOUDA AMOU OU, GENEVIEVE GINY · 2017 to 2021
$8.3M
HIV-1 Q23.17 Env: Engineering a novel immunogen to elicit broadly neutralizing antibodiesR01AI165080 · NIAID · UNIVERSITY OF PENNSYLVANIA · PI GEORGE M SHAW · 2021 to 2026
$6.6M
Modeling Viral and T Lymphocyte DynamicsR01OD011095 · OD · TRIAD NATIONAL SECURITY, LLC · PI PERELSON, ALAN S · 2012 to 2024
$5.0M
Reverse Vaccinology in SHIV Infected Macaques as a Molecular Guide for HIV-1 Vaccine DesignR01AI160607 · NIAID · UNIVERSITY OF PENNSYLVANIA · PI SHAW, GEORGE M · 2021 to 2024
$3.2M
Quantitative Methods for HIV/AIDS ResearchR25AI140495 · NIAID · DUKE UNIVERSITY · PI Cliburn C Chan, Gina-Maria Pomann · 2018 to 2026
$2.8M
SIV cervicovaginal transmission dynamicsR21AI143443 · NIAID · PENNSYLVANIA STATE UNIVERSITY, THE · PI CONWAY, JESSICA M · 2020 to 2021
$427k
NIAID NIH HHS P01 AI131276NIAID NIH HHS P30 AI064518NIAID NIH HHS R01 AI160607NIAID NIH HHS R01 AI165080NIAID NIH HHS R21 AI143443NIAID NIH HHS R25 AI140495NIAID NIH HHS U01 AI169767NIH HHS P51 OD011132NIH HHS R01 OD011095NIH HHS U42 OD011023
6 · The paper itself

Abstract

While the benefits of early antiretroviral therapy (ART) initiation in perinatally infected infants are well documented, early initiation is not always possible in postnatal pediatric HIV infections. The timing of ART initiation is likely to affect the size of the latent viral reservoir established, as well as the development of adaptive immune responses, such as the generation of neutralizing antibody responses against the virus. How these parameters impact the ability of infants to control viremia and the time to viral rebound after ART interruption is unclear and has never been modeled in infants. To investigate this question we used an infant nonhuman primate Simian/Human Immunodeficiency Virus (SHIV) infection model. Infant Rhesus macaques (RMs) were orally challenged with SHIV.C.CH505 375H dCT and either given ART at 4-7 days post-infection (early ART condition), at 2 weeks post-infection (intermediate ART condition), or at 8 weeks post-infection (late ART condition). These infants were then monitored for up to 60 months post-infection with serial viral load and immune measurements. To gain insight into early after analytic treatment interruption (ATI), we constructed mathematical models to investigate the effect of time of ART initiation in delaying viral rebound when treatment is interrupted, focusing on the relative contributions of latent reservoir size and autologous virus neutralizing antibody responses. We developed a stochastic mathematical model to investigate the joint effect of latent reservoir size, the autologous neutralizing antibody potency, and CD4+ T cell levels on the time to viral rebound for RMs rebounding up to 60 days post-ATI. We find that the latent reservoir size is an important determinant in explaining time to viral rebound in infant macaques by affecting the growth rate of the virus. The presence of neutralizing antibodies can also delay rebound, but we find this effect for high potency antibody responses only. Finally, we discuss the therapeutic implications of our findings.

Indexed as

Antibodies, NeutralizingMacaca mulattaSimian Acquired Immunodeficiency SyndromeSimian Immunodeficiency VirusViral LoadAnimalsAnimals, NewbornAnti-Retroviral AgentsDisease Models, AnimalHIV InfectionsViremiaAntibodies, NeutralizingAnti-Retroviral AgentsLatent reservoirMathematical modelingNeutralizing antibodiesPediatric HIVViral rebound

Identifiers

PMID38964130
PMCPMC11518701

What OpenQuestion holds

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LicenceCC BY-NC-ND
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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 OpenQuestion graph.