The role of drug kinetics on the evolution of resistance.

Emergence of drug resistance due to treatment non-adherence is a problem especially in chronic prolonged viral infections like the Human Immunodeficiency virus (HIV) and Hepatitis B (HBV) and C (HCV) viruses. Long acting drugs are being developed as one way to address this problem. Though this promises to be useful in the context of treatment adherence, we do not yet know how this would affect resistance.

With this in mind, we analyze the effect of dosing intervals on the establishment of drug resistance due to mutants existing prior to treatment (pre-existing) and those that are produced during treatment (rescue) in the presence of time-dependent drug profiles.

We find that there exists an initial time-frame after treatment initiation that has the most influence on the establishment probability of the drug resistant strain. Depending upon the nature of the drug kinetics during this time as well as infection parameters, increasing the dosing interval might be better or worse for the establishment of resistance. Our results suggest that drug kinetics affect selection and competition in the system in a complicated manner and should be factored in while designing new treatment strategies.