Design of an optimal combination therapy with broadly neutralizing antibodies to suppress HIV-1

Abstract
Data availability
Article and author information
Metrics

Abstract

Infusion of broadly neutralizing antibodies (bNAbs) has shown promise as an alternative to anti-retroviral therapy against HIV. A key challenge is to suppress viral escape, which is more effectively achieved with a combination of bNAbs. Here, we propose a computational approach to predict the efficacy of a bNAb therapy based on the population genetics of HIV escape, which we parametrize using high-throughput HIV sequence data from bNAb-naive patients. By quantifying the mutational target size and the fitness cost of HIV-1 escape from bNAbs, we predict the distribution of rebound times in three clinical trials. We show that a cocktail of three bNAbs is necessary to effectively suppress viral escape, and predict the optimal composition of such bNAb cocktail. Our results offer a rational therapy design for HIV, and show how genetic data can be used to predict treatment outcomes and design new approaches to pathogenic control.

Data availability

The current manuscript is a computational study, so no data have been generated for this manuscript. Reference to the previously published data used in this manuscript is provided. Modelling code is uploaded on GitHub at https://github.com/StatPhysBio/HIVTreatmentOptimization, and in the Julia package https://github.com/StatPhysBio/EscapeSimulator.

The following previously published data sets were used

1. Zanini et al
(2015) Project: PRJEB9618
European Nucleotide Archive, Accession no: PRJEB9618.

https://www.ebi.ac.uk/ena/browser/view/PRJEB9618?show=reads
1. Caskey et al
(2015) HIV-1 isolate 2A1_DB7_02 from USA envelope glycoprotein (env) gene, partial cds
GeneBank, accession no: KX016803.

https://www.ncbi.nlm.nih.gov/nuccore/1036347437
1. Caskey et al
(2017) Antibody 10-1074 suppresses viremia in HIV-1-infected individuals
GeneBank, accession no: KY323724-KY324834.

https://www.ncbi.nlm.nih.gov/nuccore/KY323724
1. Bar-On et al
(2018) Safety and antiviral activity of combination HIV-1 broadly neutralizing antibodies in viremic individuals
GeneBank, accession no: MH632763 - MH633255.

https://www.ncbi.nlm.nih.gov/nuccore/MH632763

Article and author information

Author details

Colin LaMont

Max Planck Institute for Dynamics and Self-Organization, Göttingen, Germany

Competing interests
No competing interests declared.
Jakub Otwinowski

Max Planck Institute for Dynamics and Self-Organization, Göttingen, Germany

Competing interests
No competing interests declared.
Kanika Vanshylla

University of Cologne, Cologne, Germany

Competing interests
No competing interests declared.
Henning Gruell

University of Cologne, Cologne, Germany

Competing interests
No competing interests declared.

"This ORCID iD identifies the author of this article:" 0000-0002-0725-7138
Florian Klein

University of Cologne, Cologne, Germany

Competing interests
No competing interests declared.
Armita Nourmohammad

Department of Physics, University of Washington, Seattle, United States

For correspondence
armita@uw.edu

Competing interests
Armita Nourmohammad, Reviewing editor, eLife.

"This ORCID iD identifies the author of this article:" 0000-0002-6245-3553

Funding

Deutsche Forschungsgemeinschaft (1310)

Armita Nourmohammad

National Science Foundation (2045054)

Armita Nourmohammad

1Max Planck Institute for Dynamics and Self-organization (open access funding)

Colin LaMont
Jakub Otwinowski

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Copyright

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.