Efficacy, Pharmacokinetics, and Safety Over 48 Weeks With Ibalizumab-Based Therapy in Treatment-Experienced Adults Infected With HIV-1: A Phase 2a Study

Ibalizumab, a humanized monoclonal antibody targeting CD4, blocks HIV-1 entry into cells and is the first Food and Drug Adminstration-approved long-acting agent for HIV-1 treatment. In this phase 2a study, 82 HIV-infected adults failing antiretroviral therapy were assigned an individually optimized background regimen (OBR) and randomized 1:1:1 to arm A (15 mg/kg ibalizumab q2wk), arm B (10 mg/kg weekly for 9 weeks, then q2wk), or placebo. Subjects with an inadequate response at week 16 were permitted to cross over to a new OBR plus 15 mg/kg ibalizumab q2wk. At week 16, viral load (VL) reduction was significantly greater than placebo (0.26 log(10)) in arms A (1.07 log(10); P = 0.002) and B (1.33 log(10); P < 0.001); CD4(+) T cell counts increased significantly in arm A. After week 16, 11/27 (arm B) and 19/27 (placebo) subjects crossed over to OBR plus 15 mg/kg ibalizumab; 8/28 in arm A initiated a new OBR. Ibalizumab treatment resulted in VL reduction at week 24 (−0.77 and −1.19 log(10) for arms A and B, respectively, versus −0.32 log(10) for placebo) and 48 weeks (−0.54 and −0.77 versus −0.22 log(10)). Compared with placebo, VL differences were statistically significant for arm B at week 24 (P = 0.001) and week 48 (P = 0.027). CD4(+) T cell counts increased significantly by week 48 in both arm A and arm B, relative to placebo. No ibalizumab-related serious adverse events were reported. The durable antiviral activity and tolerability of ibalizumab support its use in treating individuals harboring multidrug-resistant HIV-1.