在接受过治疗的艾滋病毒感染者中，一名患者在功能单药治疗期间出现比克替拉韦耐药性，在短暂治疗中断后被一种古老的野生型毒株迅速取代。
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.
作者信息
Faré Pietro B, Ziltener Gabriela, Bergadà Pijuan Judith, Abela Irene A, Hirsch Britta L, Huber Michael, Nemeth Johannes, Günthard Huldrych F
机构信息
Department of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, 8091 Zurich, Switzerland.
Institute of Medical Virology, University of Zurich, 8057 Zurich, Switzerland.
出版信息
Viruses. 2025 May 13;17(5):699. doi: 10.3390/v17050699.
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.
一名接受过多种治疗、依从性高且感染艾滋病毒超过25年的患者，对包括比克替拉韦（BIC）在内的所有四大类抗逆转录病毒疗法（ART）都产生了耐药突变。这导致在包含BIC和多拉韦林（DOR）的四联疗法中出现病毒治疗失败。耐药性的出现与M184V、胸苷类似物突变（TAMs）、非核苷类逆转录酶抑制剂突变（108I、234I、318F）和整合酶链转移抑制剂突变（T97A、G140S、Q148H、G149A）有关，可能是由于二价阳离子相互作用导致BIC水平未达最佳所致。在为期两个月的抗逆转录病毒治疗中断期间，耐药病毒迅速被一种古老的野生型毒株取代。尽管对所有四类抗逆转录病毒疗法均耐药，但一种包括福斯特韦尔（fostemsavir）的基因型适配挽救方案在七个月内实现了病毒抑制。
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