Speaker
Description
Due to their long-half life and breadth of coverage, broadly neutralizing antibodies (bnAbs) are increasingly studied for both treatment and prevention of HIV-1 infection. Recent clinical studies have shown potent neutralization with corresponding multiple log-declines following single or multiple administrations of bnAbs in viremic participants. While bnAb concentrations typically exhibit biphasic decline during these trials, bnAb pharmacokinetics significantly differ between HIV-1 positive and negative individuals during phase I trials. These differences are hypothesized to be driven by nonlinear interactions between bnAb and circulating virus that result in increased clearance of bnAb-virus complexes. I’ll discuss a series of mechanistic models that quantify these nonlinear effects across three phase I clinical trials of distinct bnAbs. I’ll show how the dynamics of these bnAb-virus complexes can explain nonlinear viral dynamics during early bnAb treatment and implicate the immune system in the viral dynamics following bnAb treatment.
