Design of an optimal combination therapy with broadly neutralizing antibodies to suppress HIV-1.
Elife
; 112022 07 19.
Article
en En
| MEDLINE
| ID: mdl-35852143
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.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Infecciones por VIH
/
VIH-1
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
Elife
Año:
2022
Tipo del documento:
Article
País de afiliación:
Alemania