Chen Nan-Yu, Cheng Chien-Yu, Lo Shih-Hao, Lu Po-Liang, Yang Chia-Jui, Tseng Cheng-Yin, Tsai Hung-Chin, Wu Ting-Shu, Hsiao Yu-Hsiang, Liu Zhuo-Hao, Ku Stephane Wen-Wei
Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan.
Taoyuan General Hospital, Ministry of Health and Welfare, Taoyuan, Taiwan.
Open Forum Infect Dis. 2025 Jan 17;12(2):ofaf028. doi: 10.1093/ofid/ofaf028. eCollection 2025 Feb.
It is generally believed that HIV-1 capsid inhibitor-naïve populations are susceptible to capsid inhibitors. Moreover, conventional HIV-1 resistance genotyping does not include the CA region, leading to limited surveillance data.
We conducted a retrospective study to investigate the presence of mutations at positions associated with capsid inhibitor resistance before the introduction of the first HIV-1 capsid inhibitor, lenacapavir, in Taiwan. Capsid mutations at positions L56, N57, M66, Q67, K70, N74, A105, and T107 were analyzed using a local HIV-1 database that encompasses near-full-length next-generation sequencing data of both antiretroviral therapy (ART)-naïve and -experienced individuals with HIV-1, collected between 2017 and 2023 in Northern Taiwan.
A total of 287 CA sequences were analyzed. Mutations at positions associated with capsid inhibitor resistance were rare, found in 4.5% (7/156) of ART-naïve and 5.3% (7/131) of ART-experienced individuals, mainly as accessory mutations or polymorphisms. Notably, a Q67H mutation was found in an ART-naïve individual at a frequency of 26.8%, while a Q67R mutation, with unclear clinical implications, appeared at 2.8% in an ART-experienced case.
This result indicated low prevalence yet undeniable existence of naturally occurring capsid inhibitor resistance-related mutations in capsid inhibitor-naïve individuals with HIV-1.
一般认为，未接触过HIV-1衣壳抑制剂的人群对衣壳抑制剂敏感。此外，传统的HIV-1耐药基因分型不包括CA区域，导致监测数据有限。
我们进行了一项回顾性研究，以调查在台湾首次引入HIV-1衣壳抑制剂来那卡帕韦之前，与衣壳抑制剂耐药相关位置的突变情况。使用一个本地HIV-1数据库分析L56、N57、M66、Q67、K70、N74、A105和T107位置的衣壳突变，该数据库包含2017年至2023年在台湾北部收集的未接受抗逆转录病毒治疗（ART）和接受过ART的HIV-1感染者的近全长二代测序数据。
共分析了287条CA序列。与衣壳抑制剂耐药相关位置的突变很少见，在未接受ART的个体中占4.5%（7/156），在接受过ART的个体中占5.3%（7/131），主要为辅助性突变或多态性。值得注意的是，在一名未接受ART的个体中发现Q67H突变的频率为26.8%，而在一名接受过ART的病例中出现临床意义不明的Q67R突变的频率为2.8%。
这一结果表明，在未接触过衣壳抑制剂的HIV-1感染者中，自然发生的与衣壳抑制剂耐药相关的突变虽然发生率低，但确实存在。
