ArticlePLoS computational biology2020
Mathematical modeling to reveal breakthrough mechanisms in the HIV Antibody Mediated Prevention (AMP) trials.
Article in PLoS computational biology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers, 1 of them a synthesis that pooled it.
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Who cites it
24 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Optimizing clinical dosing of combination broadly neutralizing antibodies for HIV prevention.PLoS computational biology · 2022Pooled it
- Mathematical Modeling of Within-Host, Untreated, Cytomegalovirus Infection Dynamics after Allogeneic Transplantation.Viruses · 2021Trial
- Modeling quantifies in vivo neutralization, Fc-mediated killing, and resistance in human clinical trials of five anti-HIV broadly neutralizing antibodies.bioRxiv : the preprint server for biology · 2026Article
- Clinical trial simulation of antiviral drugs.Journal of virology · 2026Review
- A Nonparametric Approach to Practical Identifiability of Nonlinear Mixed Effects Models.Bulletin of mathematical biology · 2026Article
- Clonal heterogeneity and antigenic stimulation shape persistence of the latent reservoir of HIV.PLoS computational biology · 2025Article
- Resistance mutations that distinguish HIV-1 envelopes with discordant VRC01 phenotypes from multi-lineage infections in the HVTN703/HPTN081 trial: implications for cross-resistance.Journal of virology · 2025Article
- Modelling Role of Protective and Nonprotective HLA Allele Inducing Different HIV Infection Outcomes.Bulletin of mathematical biology · 2024Article
- A unifying model to explain frequent SARS-CoV-2 rebound after nirmatrelvir treatment and limited prophylactic efficacy.Nature communications · 2024Article
- A unifying model to explain high nirmatrelvir therapeutic efficacy against SARS-CoV-2, despite low post-exposure prophylaxis efficacy and frequent viral rebound.medRxiv : the preprint server for health sciences · 2024Article
- Modeling resistance to the broadly neutralizing antibody PGT121 in people living with HIV-1.PLoS computational biology · 2024Article
- High monoclonal neutralization titers reduced breakthrough HIV-1 viral loads in the Antibody Mediated Prevention trials.Nature communications · 2023Article
- Application of the SLAPNAP statistical learning tool to broadly neutralizing antibody HIV prevention research.iScience · 2023Article
- Article
- Pharmacokinetic serum concentrations of VRC01 correlate with prevention of HIV-1 acquisition.EBioMedicine · 2023Article
- Design of an optimal combination therapy with broadly neutralizing antibodies to suppress HIV-1.eLife · 2022Article
- Reappraising the Value of HIV-1 Vaccine Correlates of Protection Analyses.Journal of virology · 2022Review
- Estimation of the in vivo neutralization potency of eCD4Ig and conditions for AAV-mediated production for SHIV long-term remission.Science advances · 2022Article
- Predicting in vivo escape dynamics of HIV-1 from a broadly neutralizing antibody.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Timing HIV infection with a simple and accurate population viral dynamics model.Journal of the Royal Society, Interface · 2021Article
Corrections and comments
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Authors and funding
14 authors.
Funding
Abstract
The ongoing Antibody Mediated Prevention (AMP) trials will uncover whether passive infusion of the broadly neutralizing antibody (bNAb) VRC01 can protect against HIV acquisition. Previous statistical simulations indicate these trials may be partially protective. In that case, it will be crucial to identify the mechanism of breakthrough infections. To that end, we developed a mathematical modeling framework to simulate the AMP trials and infer the breakthrough mechanisms using measurable trial outcomes. This framework combines viral dynamics with antibody pharmacokinetics and pharmacodynamics, and will be generally applicable to forthcoming bNAb prevention trials. We fit our model to human viral load data (RV217). Then, we incorporated VRC01 neutralization using serum pharmacokinetics (HVTN 104) and in vitro pharmacodynamics (LANL CATNAP database). We systematically explored trial outcomes by reducing in vivo potency and varying the distribution of sensitivity to VRC01 in circulating strains. We found trial outcomes could be used in a clinical trial regression model (CTRM) to reveal whether partially protective trials were caused by large fractions of VRC01-resistant (IC50>50 μg/mL) circulating strains or rather a global reduction in VRC01 potency against all strains. The former mechanism suggests the need to enhance neutralizing antibody breadth; the latter suggests the need to enhance VRC01 delivery and/or in vivo binding. We will apply the clinical trial regression model to data from the completed trials to help optimize future approaches for passive delivery of anti-HIV neutralizing antibodies.
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Registered trials
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.