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

Abstract

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 log10) in arms A (1.07 log10; P = 0.002) and B (1.33 log10; 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 log10 for arms A and B, respectively, versus -0.32 log10 for placebo) and 48 weeks (-0.54 and -0.77 versus -0.22 log10). 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.

Trial registration: ClinicalTrials.gov NCT00089700.

Conflict of interest statement

R.L.H. is a speaker and consultant of Theratechnologies. S.W. is an employee of TaiMed Biologics USA, Inc. S.T.L. was a former employee and shareholder of TaiMed Biologics USA, Inc. during this clinical study. R.B.C. is an employee of Theratechnologies Inc. The remaining authors have no conflicts of interest to disclose.

Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc.

Figures

FIGURE 1.

Mean antiviral (A) and immunological responses (B) at week 24 and 48 and Kaplan–Meier estimates of TLOVR (C). Missing data were imputed using the last observation carried forward (LOCF). P-values are in comparison with the placebo arm at the same time point. For TLOVR analysis, individuals who never showed a virologic response (≥0.5 log10 reduction in HIV-1 RNA) were considered to have failed at t = 0. The dashed line indicates 50%.

FIGURE 2.

Serum ibalizumab trough concentration over time in arms A and B. Note that during the initial weeks of the study, dosing with ibalizumab was more frequent in arm B (solid triangles) than in arm A (solid circles).