Lenacapavir and the novel HIV-1 capsid inhibitors: an emerging therapy in the management of multidrug-resistant HIV-1 virus

Purpose of reviewThe aim of this study was to summarize current evidence regarding lenacapavir, a first in class HIV-1 capsid inhibitor, and its role as an emergent therapy for the treatment of HIV-1 infection.Recent findingsHIV-1 capsid inhibitors (of which lenacapavir is the first in class) has been postulated to have activity against multidrug resistant HIV-1 viral isolates. Initial results from the phase 3 trial CAPELLA (combining oral and subcutaneous lenacapavir alongside failing drug therapies) suggest that there may be a role for these novel agents in a cohort of patients living with HIV-1 infection (PLWH) for whom multidrug resistance has previously been a barrier to effective therapy. Despite emergent lenacapavir resistance mutations detected in some study participants, virological suppression was still potentially attainable, offering some hope to PLWH with limited antiviral regimens available. Initial results from the CALIBRATE trial show promise for the role of lenacapavir-containing regimens in a treatment-naive cohort as well.Lenacapavir may prove to be an adjunctive agent in the management of PLWH with significant HIV-1 drug resistance.