Introduction: Lenacapavir, the compound reviewed in this paper, is a novel, potent, and long-acting first-in-class HIV-1 capsid inhibitor that was granted a breakthrough therapy designation for HIV treatment by the U.S. Food and Drug Administration in May 2019. Lenacapavir was subsequently approved, in combination with other antiretroviral agents, for the treatment of multidrug-resistant HIV in people with HIV who have limited treatment options due to safety, intolerance, and resistance considerations, based on clinical trial data, which demonstrated its efficacy, tolerability, and safety for that population.
Areas covered: This review draws upon published and unpublished data of lenacapavir (GS-6207) to discuss its chemistry, mechanism of action, pharmacokinetic, and pharmacodynamic properties, as well as efficacy and safety observed in clinical trials; and an expert opinion section discusses its clinical uses, advantages, limitations, and potential future applications.
Expert opinion: Lenacapavir should be used in combination with at least one or two additional fully active agents, where possible, and adherence support is critical for selected companion drugs (particularly if self-administered) to optimize efficacy and prevent treatment-emergent resistance to lenacapavir. Providers should pay attention to drug-drug interactions when initiating lenacapavir.
Keywords: HIV infection; Lenacapavir; antiretrovirals; drug resistance; treatment.