Lin Yaqing, Ling Xuemei, Li Linghua, Xin Ruolei, Hu Fengyu, Li Junbin, Li Jiaojiao, Li Feng, Lan Yun
Institute of Infectious Diseases, Guangzhou Eighth People's Hospital, Guangzhou Medical University, Guangzhou, People's Republic of China.
Guangzhou Institute of Clinical Infectious Diseases, Infectious Disease Center, Guangzhou Eighth People's Hospital, Guangzhou Medical University, Guangzhou, People's Republic of China.
Infect Drug Resist. 2024 Oct 2;17:4271-4277. doi: 10.2147/IDR.S484383. eCollection 2024.
The capsid inhibitor (CAI) lenacapavir (LEN) was approved for use in 2022, yet there are few reports about its drug resistance mutations (DRMs) and sensitivity.
To delineate the prevalence of CAI DRMs and drug susceptibility among HIV-1 infected individuals living in Guangdong, China.
A total of 1035 individuals with HIV-1 infection, including 660 highly Active Anti-Retroviral Therapy (HAART) naive individuals and 375 hAART experienced individuals whose protease (PR)/ reverse transcriptase (RT) fragments were amplified successfully during drug resistance surveillance between October 2021 and December 2023, were randomly included in this study. The entire HIV-1 gene was amplified from plasma in LEN-naive individuals with or without antiretroviral therapy. The epidemiological and demographic information of the enrolled individuals were collected. The Stanford HIV Drug Resistance Database HIVdb program for Capsid was used to interpret the CAI DRMs and the LEN susceptibility.
Among 1035 samples, 805 sequences were amplified, sequenced and assembled successfully from 518 hAART drugs naive individuals and 287 hAART drugs experienced individuals. Among them, 0.50% (4/805) carried at least one CAI DRM, of which 0.19% (1/518) from HAART naive individuals and 1.05% (3/287) from HAART experienced individuals. Among the individuals with CAI DRMs, two patients carried CAI major mutations (Q67H) conferring intermediate resistance to LEN and two patients carried CAI accessory mutation (T107A) conferring low level resistance to LEN.
Extremely low prevalence of CAI DRMs was detected among people living with HIV (PLWH) in Guangdong, China. Our observations indicate that LEN application may be promising when used in clinical practice in China. Before the administration of LEN, there is no need to consider detecting CAI mutations in PLWH through DRM examination for the time being.
衣壳抑制剂（CAI）来那卡帕韦（LEN）于2022年获批使用，但关于其耐药性突变（DRM）和敏感性的报道较少。
明确中国广东省HIV-1感染者中CAI DRM的流行情况和药物敏感性。
本研究随机纳入了1035例HIV-1感染者，其中包括660例未接受过高效抗逆转录病毒治疗（HAART）的患者和375例接受过HAART治疗的患者，这些患者在2021年10月至2023年12月的耐药监测期间蛋白酶（PR）/逆转录酶（RT）片段成功扩增。从接受或未接受抗逆转录病毒治疗的未使用过LEN的个体血浆中扩增整个HIV-1基因。收集纳入个体的流行病学和人口统计学信息。使用斯坦福HIV耐药数据库HIVdb衣壳程序来解读CAI DRM和LEN敏感性。
在1035份样本中，成功从518例未接受过HAART治疗的患者和287例接受过HAART治疗的患者中扩增、测序并组装了805条序列。其中，0.50%（4/805）携带至少一种CAI DRM，其中未接受过HAART治疗的患者中为0.19%（1/518），接受过HAART治疗的患者中为1.05%（3/287）。在携带CAI DRM的个体中，两名患者携带对LEN具有中等耐药性的CAI主要突变（Q67H），两名患者携带对LEN具有低水平耐药性的CAI辅助突变（T107A）。
在中国广东省的HIV感染者（PLWH）中检测到CAI DRM的流行率极低。我们的观察结果表明，LEN在中国临床实践中使用可能具有前景。在使用LEN之前，目前无需考虑通过DRM检测来检测PLWH中的CAI突变。
