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

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.