Evidence map›Paper›PMID 38551976›Full record

ArticlePLoS computational biology2024

Modeling resistance to the broadly neutralizing antibody PGT121 in people living with HIV-1.

Tyler Cassidy, Kathryn E Stephenson, Dan H Barouch, Alan S Perelson

Open access · goldAbstract read
In one paragraph

Article in PLoS computational biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
1.5field-weighted citation impact, top 19% 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

4 citing papers in PubMed, 5 citations in OpenAlex.

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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

4 authors at 3 institutions in 2 countries.

Tyler CassidySchool of Mathematics, University of Leeds, Leeds, United Kingdom.ORCID 0000-0003-0757-0017
Kathryn E StephensonCenter for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, Massachusetts, United States of America.
Dan H BarouchCenter for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, Massachusetts, United States of America.
Alan S PerelsonTheoretical Biology and Biophysics, Los Alamos National Laboratory, Los Alamos, New Mexico, United States of America.ORCID 0000-0002-2455-0002
Beth Israel Deaconess Medical Center · USLos Alamos National Laboratory · USUniversity of Leeds · GB

Funding

Reversing Immune Dysfunction for HIV-1 EradicationUM1AI164561 · NIAID · SCRIPPS RESEARCH INSTITUTE, THE · PI SUMIT K CHANDA, Paula M Cannon · 2021 to 2026
$30.0M
I4C 2.0: Immunotherapy for CureUM1AI164556 · NIAID · BETH ISRAEL DEACONESS MEDICAL CENTER · PI Dan H. Barouch, John W Mellors · 2021 to 2026
$28.0M
Understanding reservoir dynamics through analysis of viral decay processesP01AI169615 · NIAID · JOHNS HOPKINS UNIVERSITY · PI ALAN S PERELSON · 2022 to 2026
$9.5M
NHP CoreP01AI177687 · NIAID · BETH ISRAEL DEACONESS MEDICAL CENTER · PI Boris Dominik Juelg · 2023 to 2026
$7.4M
Modeling Viral and T Lymphocyte DynamicsR01OD011095 · OD · TRIAD NATIONAL SECURITY, LLC · PI PERELSON, ALAN S · 2012 to 2024
$5.0M
Single-Cell Analysis of the HIV/SIV ReservoirR01AI149670 · NIAID · BETH ISRAEL DEACONESS MEDICAL CENTER · PI BAROUCH, DAN H., SHALEK, ALEX K · 2020 to 2024
$4.6M
Immune System Modeling/HIVR01AI028433 · NIAID · UNIVERSITY OF CALIF-LOS ALAMOS NAT LAB · PI PERELSON, ALAN S · 1990 to 2021
$3.7M
Diversity of Immune Responses Elicited by HIV VaccinesK23AI114381 · NIAID · BETH ISRAEL DEACONESS MEDICAL CENTER · PI STEPHENSON, KATHRYN ELAINE · 2014 to 2018
$818k
NIAID NIH HHS K23 AI114381NIAID NIH HHS P01 AI169615NIAID NIH HHS P01 AI177687NIAID NIH HHS R01 AI028433NIAID NIH HHS R01 AI149670NIAID NIH HHS UM1 AI164556NIAID NIH HHS UM1 AI164561NIH HHS R01 OD011095
6 · The paper itself

Abstract

PGT121 is a broadly neutralizing antibody in clinical development for the treatment and prevention of HIV-1 infection via passive administration. PGT121 targets the HIV-1 V3-glycan and demonstrated potent antiviral activity in a phase I clinical trial. Resistance to PGT121 monotherapy rapidly occurred in the majority of participants in this trial with the sampled rebound viruses being entirely resistant to PGT121 mediated neutralization. However, two individuals experienced long-term ART-free viral suppression following antibody infusion and retained sensitivity to PGT121 upon viral rebound. Here, we develop mathematical models of the HIV-1 dynamics during this phase I clinical trial. We utilize these models to understand the dynamics leading to PGT121 resistance and to identify the mechanisms driving the observed long-term viral control. Our modeling highlights the importance of the relative fitness difference between PGT121 sensitive and resistant subpopulations prior to treatment. Specifically, by fitting our models to data, we identify the treatment-induced competitive advantage of previously existing or newly generated resistant population as a primary driver of resistance. Finally, our modeling emphasizes the high neutralization ability of PGT121 in both participants who exhibited long-term viral control.

Indexed as

HIV-1HIV InfectionsAntibodies, NeutralizingBroadly Neutralizing AntibodiesHIV AntibodiesHumansModels, TheoreticalAntibodies, NeutralizingBroadly Neutralizing AntibodiesHIV Antibodies

Identifiers

PMID38551976
PMCPMC11006161
OpenAlexW4393318918

What OpenQuestion 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 OpenQuestion graph.