Antiviral Activity of Lenacapavir Against Human Immunodeficiency Virus Type 2 (HIV-2) Isolates and Drug-Resistant HIV-2 Mutants

The activity of lenacapavir against human immunodeficiency virus type 1 (HIV-1) has been extensively evaluated in vitro, but comparable data for human immunodeficiency virus type 2 (HIV-2) are scarce. We determined the anti-HIV-2 activity of lenacapavir using single-cycle infections of MAGIC-5A cells and multicycle infections of a T-cell line. Lenacapavir exhibited low-nanomolar activity against HIV-2, but was 11- to 14-fold less potent against HIV-2 in comparison to HIV-1. Mutations in HIV-2 that confer resistance to other antiretrovirals did not confer cross-resistance to lenacapavir. Although lenacapavir-containing regimens might be considered for appropriate patients with HIV-2, more frequent viral load and/or CD4 testing may be needed to assess clinical response. Lenacapavir is a first-in-class capsid inhibitor that acts at multiple steps in the HIV-1 replication cycle. Our findings show that lenacapavir is active against HIV-2 isolates and drug-resistant HIV-2 mutants in culture, albeit with reduced potency relative to HIV-1.