Current Drugs to Treat Infections with Herpes Simplex Viruses-1 and -2.

Herpes simplex viruses-1 and -2 (HSV-1 and -2) are two of the three human alphaherpesviruses that cause infections worldwide. Since both viruses can be acquired in the absence of visible signs and symptoms, yet still result in lifelong infection, it is imperative that we provide interventions to keep them at bay, especially in immunocompromised patients. While numerous experimental vaccines are under consideration, current intervention consists solely of antiviral chemotherapeutic agents. This review explores all of the clinically approved drugs used to prevent the worst sequelae of recurrent outbreaks by these viruses.

Acyclovir, cidofovir, and amenamevir have additive antiviral effects on herpes simplex virus TYPE 1.

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 populations 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 drug 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 study tested the combination of acyclovir/cidofovir/amenamevir, the last drug being a new antiherpetic that targets the helicase-primase complex to prevent replication of viral DNA, for multidrug intervention. We used the design of experiments (DOE) function in Minitab to analyze the drug-drug interactions in their ability to inhibit growth of HSV-1. The DOE software was unable to detect any significant drug-drug interactions among these three antiherpetics as dosed. This would imply that these drugs could be used in combination to suppress viral replication without synergistic or antagonistic effects. This study shows that this therapy holds potential for further study and that DOE software is a potentially useful tool for determining complex drug-drug interactions.

Volatile Acid-Solvent Evaporation (VASE): Molecularly Homogeneous Distribution of Acyclovir in a Bioerodable Polymer Matrix for Long-Term Treatment of Herpes Simplex Virus-1 Infections.

Treatment for herpes simplex virus-1 and -2 (HSV-1 and -2) patients who suffer from recurrent outbreaks consists of multiple daily doses of the antiviral drugs acyclovir (ACV), penciclovir, or their more orally bioavailable derivatives valacyclovir or famciclovir. Drug troughs caused by missed doses may result in viral replication, which can generate drug-resistant mutants along with clinical sequelae. We developed a molecularly homogeneous mixture of ACV with the bioerodable polymer polycaprolactone. Through scanning electron microscopy, infrared spectroscopy, gel permeation chromatography, 1H NMR, and differential scanning calorimetry, our method of combining drug and polymer, termed Volatile Acid-Solvent Evaporation (VASE), does not compromise the integrity of polymer or drug. Furthermore, VASE creates materials that deliver therapeutic amounts of drug consistently for approximately two months. Devices with high enough drug loads diminish primary infection of HSV-1 in Vero cells to the same level as seen with a single dose of ACV. Our data will lead to further experiments in animal models, demonstrating efficacy in preventing reactivation of these viruses with a single intervention, and with other antiviral drugs amenable to such manipulation. Additionally, this type of treatment would leave no trace after its useful lifetime, as drug is released and polymer matrix is degraded in vivo.