Three-dimensional analysis of combination drug therapy for Herpes simplex 1

Abstract

Herpes Simplex Virus-1 (HSV-1) affects a large portion of the global population and has been shown to cause more severe symptoms in immunocompromised patients. It is in immunocompromised population that HSV-1 has shown to have higher rates of resistance to the most commonly used antiherpetics, such as acyclovir/valacyclovir/penciclovir/ famciclovir. The development of HSV-1 resistance has forced research into new antiherpetic therapies including combination drug therapies. One potential complication of multidrug therapies is the existence of drug-drug interactions, as more drugs are used in the therapy, those interactions tend to become more complicated. This is the first study to use the design of experiments (DOE) function in Minitab to analyze the drug-drug interactions in a triple drug therapy for HSV-1. This study tested the combinations of acyclovir/cidofovir/nelfinavir and acyclovir/cidofovir/ amenamevir, the last drug being a new antiherpetic that targets the helicase-primase complex to prevent replication of viral DNA. The DOE software was unable to detect any significant drug-drug interactions among these three antiherpetics. This study shows that this therapy could potentially be used in patients, while also showing DOE software as a potential method for determining complex drug-drug interactions.