A Nature Communications study detailed recurrent and novel evolutionary pathways by which HIV‑1 can acquire resistance to lenacapavir, the long‑acting capsid inhibitor. Researchers identified mutations and escape combinations that reduce drug susceptibility and outlined implications for surveillance and combination therapy strategies. The findings urge clinicians and developers to monitor resistance patterns as lenacapavir deployment expands and to consider adaptive combination regimens and diagnostic sequencing to preserve the drug’s long‑term utility.