학술논문

Design of an optimal combination therapy with broadly neutralizing antibodies to suppress HIV-1.
Document Type
Article
Source
eLife. 9/12/2022, p1-47. 47p.
Subject
*HIV
*BASE pairs
*ANTIRETROVIRAL agents
*IMMUNOGLOBULINS
*POPULATION genetics
Language
ISSN
2050-084X
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. [ABSTRACT FROM AUTHOR]