Lenacapavir: A Novel Injectable HIV-1 Capsid Inhibitor

Patients living with multidrug-resistant (MDR) HIV have limited antiretroviral regimen options that provide durable viral suppression. Lenacapavir is a novel first-in-class inhibitor of HIV-1 capsid function with efficacy at various stages of the viral life cycle, and it is indicated for the treatment of MDR HIV-1 infection in combination with optimized background antiretroviral therapy. The favourable pharmacokinetic profile supports an every sixth month dosing interval of subcutaneous lenacapavir after an initial oral loading dose, which may advocate for continued adherence to antiretroviral therapy (ART) through the reduction of daily pill burden. The role of lenacapavir in promoting virologic suppression has been studied in patients with MDR HIV-1 on failing ART at baseline. Lenacapavir was well tolerated in clinical trials with the most common adverse effects including mild to moderate injection site reactions, gastrointestinal symptoms, and headache. Substitutions on the capsid molecule may confer resistance to lenacapavir by changing the binding potential. Cross-resistance to other antiretrovirals has not been observed. The unique mechanism of action, pharmacokinetics, and safety and efficacy of lenacapavir support its use for the management of MDR HIV-1 infection. Current studies are ongoing to evaluate the potential use of subcutaneous lenacapavir for pre-exposure prophylaxis (PrEP). Future studies will confirm the long-term clinical safety, efficacy, and resistance data for lenacapavir.