Antiviral therapy achieves almost complete effectiveness for many viral infections such as HIV and hepatitis C. Yet, treatment for other viral infections such as cytomegalovirus (CMV) and HSV-2 is characterized by partial efficacy and substantial variability in therapeutic response among infected persons.
We developed models to explain the phenomenon of breakthrough viral shedding while on antiviral agents, incorporating virologic, immunologic, pharmacokinetic, and pharmacodynamic parameters to more accurately predict antiviral agent activity. Our models are highly flexible to simulate various viral infections, and are highly predictive. This allows us to accurately simulate clinical trials and predict the relative effectiveness of different dosage regimens, with the goal of dose optimization.
Modeling approaches are also powerful for simulating the activity of infection prevention modalities. To this end, we are developing mathematical models to predict the effectiveness of the broadly neutralizing antibody VRC01 for preventing HIV infection, for dosage regimens currently under evaluation in the HIV Vaccine Trials Network (HVTN) sponsored Antibody Mediated Prevention (AMP) trials.