Combined use of ibalizumab and lenacapavir for the treatment of multidrug-resistant HIV-1: A case series

Clin Infect Dis. 2025 Nov 3:ciaf597. doi: 10.1093/cid/ciaf597. Online ahead of print.

Abstract

Background: Some individuals with human immunodeficiency virus (HIV) have acquired multidrug-resistant (MDR) strains of HIV and/or are nonadherent to antiretroviral (ARV) medication. Injectable ARVs can provide salvage therapy for those with limited therapeutic options, and may be preferred by some people with HIV (PWH). Real-world evidence may contribute to a more comprehensive understanding of the barriers to adherence and the utility of injectable ARVs in PWH. Currently there is a lack of data on combined use of injectable ibalizumab (IBA) and lenacapavir (LEN) with optimized background regimen (OBR).

Methods: A retrospective observational study examined medical charts from people living with MDR HIV-1 across eight facilities in the USA. All PWH used a combination of both IBA + LEN ± OBR for at least 6 months. Viral loads (VL) and CD4+ counts were collected.

Results: A total of 21 PWH were included. Four-class resistance at baseline was reported in 38.1% of PWH. Within 12-24 weeks of combined IBA + LEN treatment, a median reduction of -2,710 copies/mL HIV-1 RNA was observed. Median increase to CD4+ count was 67.5 cells/mm3 within 4-44 weeks of treatment initiation. Few intolerances required changes to treatment. Therapy with IBA + LEN continued for an average of 30 months and 20 months, respectively.

Conclusions: In this small group of individuals with MDR HIV who were heavily treatment-experienced and/or faced adherence challenges, the use of IBA + LEN ± OBR was well tolerated and led to clinically significant reductions in VL and improvements in CD4+ counts.

Keywords: Heavily treatment-experienced persons with HIV; Ibalizumab; Injectable antiretroviral; Lenacapavir; Multidrug-resistant HIV-1.