Infection and Drug Resistance (Oct 2024)
Lack of Resistance Mutations to the Novel HIV-1 Capsid Inhibitor Lenacapavir Among People Living with HIV in Guangdong, China
Abstract
Yaqing Lin,1,* Xuemei Ling,2,3,* Linghua Li,2,* Ruolei Xin,4 Fengyu Hu,1 Junbin Li,3 Jiaojiao Li,1 Feng Li,1,5 Yun Lan1 1Institute of Infectious Diseases, Guangzhou Eighth People’s Hospital, Guangzhou Medical University, Guangzhou, People’s Republic of China; 2Guangzhou Institute of Clinical Infectious Diseases, Infectious Disease Center, Guangzhou Eighth People’s Hospital, Guangzhou Medical University, Guangzhou, People’s Republic of China; 3Guangdong Center for Diagnosis and Treatment of AIDS, Guangzhou, People’s Republic of China; 4Institute of AIDS/STD Prevention and Control, Beijing Center for Disease Prevention and Control, Beijing, People’s Republic of China; 5Scientifc Research Center, Shanghai Public Health Clinical Center, Fudan University, Shanghai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Feng Li; Yun Lan, Email [email protected]; [email protected]: 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.Purpose: To delineate the prevalence of CAI DRMs and drug susceptibility among HIV-1 infected individuals living in Guangdong, China.Patients and Methods: 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 gag 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.Results: Among 1035 samples, 805 gag 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.Conclusion: 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.Keywords: HIV-1, capsid inhibitor, lenacapavir, drug resistance mutation, Guangdong
