Lenacapavir: a first-in-class HIV-1 capsid inhibitor

Purpose of review This review summarizes available data for lenacapavir, an investigational first-in-class agent that disrupts functioning of HIV capsid protein across multiple steps in the viral life cycle. Recent findings Lenacapavir demonstrated picomolar potency in vitro with no cross resistance to existing antiretroviral classes and potent antiviral activity in persons with HIV-1. In persons with HIV-1, there was no preexisting resistance to lenacapavir regardless of treatment history. Lenacapavir can be administered orally either daily or weekly and subcutaneously up to every 6 months. In heavily treatment-experienced persons with multidrug-resistant HIV-1 and in treatment-naive persons with HIV-1, lenacapavir in combination with other antiretroviral agents led to high rates of virologic suppression and was well tolerated. Ongoing studies are evaluating long-acting dosing of lenacapavir for treating HIV-1 in combination with other antiretrovirals and preventing HIV-1 as a single agent.

Automated summary

This review summarizes the available data for lenacapavir, a novel agent that disrupts the functioning of HIV capsid protein in multiple steps of the viral life cycle. The findings indicate that lenacapavir demonstrates potent antiviral activity against HIV-1, with no preexisting resistance observed in individuals with HIV-1 regardless of treatment history. It can be administered orally or subcutaneously, and has shown high rates of virological suppression and good tolerability when used in combination with other antiretroviral agents. Ongoing studies are exploring the potential of long-acting dosing for lenacapavir in treating HIV-1 and as a standalone agent for preventing HIV-1.