Ibalizumab plus an optimized background regimen in treatment-experienced patients infected with multidrug resistant HIV-1: A phase 3, multicenter, expanded access study.

Background: Patients infected with multidrug-resistant (MDR) HIV-1 have limited treatment options and poor clinical outcomes. For effective suppression of viral replication, regimens with distinct mechanisms of action and nonoverlapping patterns of resistance are needed.

Methods: Studies of post-attachment inhibitor ibalizumab plus optimized background regimen (OBR) are needed to evaluate efficacy and safety of long-term use in patients with MDR HIV-1, potentially providing more treatment options. Methods: TMB-311 was a multicenter, open-label, expanded access phase 3 study that provided a compassionate bridge to commercial availability of ibalizumab for patients with and without prior exposure to drug.

Results: In patients with prior exposure to ibalizumab, 23/39 (59%) had viral load (VL) <50 RNA copies/mL at study initiation and 26/34 (76%) had VL <50 copies/mL at Week 24. In ibalizumab-naïve patients receiving compassionate access, 0/38 (0%) had VL <50 copies/mL at study initiation compared to 11/24 (46%) at Week 24. Mean CD4+ cell counts increased from Baseline to Week 24 across both patient groups. Rates of serious treatment-emergent adverse events (TEAEs) up to Week 120 were low. Discontinuations due to TEAEs were 0% in the patients with prior ibalizumab exposure and 8% in those who were ibalizumab-naïve.

Conclusions: Long-term ibalizumab treatment in combination with an OBR was considered safe and well tolerated with no new safety signals identified in people living with MDR HIV-1. Additionally, ibalizumab-naïve patients experienced notable and early reductions in viral load with sustained increases in CD4+ cell counts over 24 weeks.