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Emergence of Bictegravir Resistance in a Treatment-Experienced PWH on Functional Monotherapy and Rapid Replacement by an Ancient Wild-Type Strain Following Transient Treatment Interruption
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Emergence of Bictegravir Resistance in a Treatment-Experienced PWH on Functional Monotherapy and Rapid Replacement by an Ancient Wild-Type Strain Following Transient Treatment Interruption
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Journal Article
Emergence of Bictegravir Resistance in a Treatment-Experienced PWH on Functional Monotherapy and Rapid Replacement by an Ancient Wild-Type Strain Following Transient Treatment Interruption
2025
Overview
A treatment-experienced, highly adherent person living with HIV for over 25 years developed resistance mutations against all four major ART classes, including bictegravir (BIC). This led to viral failure on a quadruple regimen including BIC and doravirine (DOR). Resistance emergence was associated with M184V, thymidine analog mutations (TAMs), NNRTI mutations (108I, 234I, 318F), and INSTI mutations (T97A, G140S, Q148H, G149A), likely driven by suboptimal BIC levels due to divalent cation interactions. During a two-month ART interruption, the resistant virus was rapidly replaced by an ancient wild-type strain. Despite resistance to all four ART classes, a genotype-adapted salvage regimen, including fostemsavir, achieved viral suppression within seven months.
Publisher
MDPI AG,MDPI
Subject
/ Aluminum
/ Amides
/ Anti-HIV Agents - pharmacology
/ Anti-HIV Agents - therapeutic use
/ Drug Resistance, Viral - genetics
/ Genotype
/ Heterocyclic Compounds, 3-Ring
/ Heterocyclic Compounds, 4 or More Rings - pharmacology
/ Heterocyclic Compounds, 4 or More Rings - therapeutic use
/ HIV Infections - drug therapy
/ HIV-1
/ Humans
/ Male
/ Methods
/ Mutation
/ Plasma
