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

To the  Editor—the publication on “Prevalence of Naturally Occurring HIV-1 Capsid Inhibitor Resistance-Related Mutations in Antiretroviral Therapy-Naïve and -Experienced Individuals in Taiwan [1]” is hereby discussed. This study's retrospective design has a number of drawbacks, despite its obvious goal of examining capsid protein alterations in a cohort of HIV-1-positive people prior to lenacapavir's official launch in Taiwan. Specifically, it may not be as generalizable to other nations or regions due to its dependence on a local database that only covers one geographic area (northern Taiwan). Furthermore, only mutation sites that had previously been linked to drug resistance were chosen for the study, which may have left out significant novel sites that have not yet been identified.

The following topics should be covered in more detail: (1) the necessity of including the capsid region (CA) in a general genotype resistance testing scheme, despite the fact that this medication is not yet commonly used; (2) whether additional trials are necessary to determine the clinical significance of mutations like Q67H or Q67R in a population that has not received capsid inhibitors; and (3) whether the criteria for which mutations should be monitored at the national level are based on regional characteristics or require a central standard. The difficulties of monitoring drug resistance prior to the release of new medications are reflected in these queries.

When analyzing the new findings, it's critical to keep in mind that the high frequency of Q67H in the ART-naïve population (26.8%) can indicate natural selection or population-specific evolutionary reasons rather than just being a straightforward polymorphism. Additionally, even if the Q67R mutation's impact on medications is unknown, its presence in the group with ART experience should encourage longitudinal research to ascertain the mutation's stability in the event that lenacapavir is introduced in the future. The study's conclusions emphasize the necessity of expanding sequencing beyond the conventional genome and the significance of creating antiretroviral surveillance systems beforehand.