Evaluation of HIV-1 capsid genetic variability and lenacapavir (GS-6207) drug resistance-associated mutations according to viral clades among drug-naive individuals.

This article focuses on the genetic variability of the HIV-1 capsid (CA) protein and the prevalence of lenacapavir (GS-6207) drug resistance-associated mutations (DRMs) among antiretroviral therapy (ART)-naive individuals across diverse HIV-1 clades. Analysis of 2,031 HIV-1 CA sequences revealed that 63% of amino acid positions were conserved, including key residues involved in binding cellular factors essential for viral replication, while lenacapavir binding sites were largely conserved except for position N183. The overall prevalence of lenacapavir DRMs was low (0.14%), with mutations M66I, Q67H, and T107N detected at very low frequencies in specific subtypes, supporting lenacapavir’s predicted effectiveness across HIV-1 clades. The study underscores the importance of conserved CA regions for monitoring emerging resistance mutations as lenacapavir advances in clinical use.