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. 2025 Jan 17;12(2):ofaf028.
doi: 10.1093/ofid/ofaf028. eCollection 2025 Feb.

Prevalence of Naturally Occurring HIV-1 Capsid Inhibitor Resistance-Related Mutations in Antiretroviral Therapy-Naïve and -Experienced Individuals in Taiwan

Nan-Yu Chen  1 , Chien-Yu Cheng  2 , Shih-Hao Lo  3 , Po-Liang Lu  3 , Chia-Jui Yang  4   5 , Cheng-Yin Tseng  6 , Hung-Chin Tsai  5   7 , Ting-Shu Wu  1 , Yu-Hsiang Hsiao  1 , Zhuo-Hao Liu  1 , Stephane Wen-Wei Ku  8
Affiliations

Prevalence of Naturally Occurring HIV-1 Capsid Inhibitor Resistance-Related Mutations in Antiretroviral Therapy-Naïve and -Experienced Individuals in Taiwan

Nan-Yu Chen et al. Open Forum Infect Dis. .

Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusions: This result indicated low prevalence yet undeniable existence of naturally occurring capsid inhibitor resistance-related mutations in capsid inhibitor-naïve individuals with HIV-1.

Keywords: HIV; capsid inhibitor; drug resistance; lenacapavir.

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Conflict of interest statement

Potential conflicts of interest. None to declare.

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