Effect of Broadly Neutralizing Antibody Exposure on HIV Rebound Following Combination Immunotherapy (CROI 2024) - Mar 17, 2024 - Abstract #618; Location: Poster hall; P1/2 | "In this pharmacokinetic/pharmacodynamic (PK/PD) analysis, we evaluated the impact of bNAb exposure, susceptibility, and antidrug antibody (ADA) formation on rebound kinetics following combination immunotherapy with a boosted DNA vaccine, lefitolimod, and bNAbs (10-1074 and VRC07-523LS) (NCT04357821), in which 7/10 individuals exhibited altered post-intervention rebound dynamics.We described plasma bNAb PK using population PK modeling approaches in Monolix software. Higher bNAb exposure (e.g., AUC, Cmax) was consistently associated with delayed viral rebound. Our results suggest that post-treatment setpoint was not driven by bNAb susceptibility and that the association of IQ90 and setpoint is driven by higher VRC07-523LS levels at the time of rebound in those who rebounded earlier and had higher setpoints. Overall, bNAb PK-PD is likely not responsible for lower observed post-treatment setpoints during this trial, suggesting the effect is likely attributable...
Human Immunodeficiency Virus • Infectious Disease
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Amelia N. Deitchman; Leonid Serebryannyy; Rowena Johnston; Lucio Gama; Marina Caskey; Elena Vendrame; Devi SenGupta; Romas Geleziunas; Jackie Reeves; Christos Petropoulos; Michel Nussenzweig; Rachel Rutishauser; Steven G. Deeks; Michael J. Peluso
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