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

• DOI: 10.1371/journal.pcbi.1011518
• Publication Date: 2024-03-29T17:36:33Z
• Authors: Tyler Cassidy; Kathryn E. Stephe...; Dan H. Barouch; Alan S. Perelson
• Keywords: QH301-705.5; Biology (General); Research Article

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