Herpes Virus Therapies

Check out Herpes Viruses for a review of types and mechanisms.

These drugs to not cure the infection. They only reduce the time to symptom alleviation, reduce viral shedding, and improve healing of lesions.

All drugs discussed bind to viral DNA polymerase and act as a DNA chain terminator.

Acyclovir

A pro-drug that is activated in infected cells. It is phosphorylated multiple times in infected cell first via viral thymidine kinase then via other cellular enzymes. Viral thymidine kinase is not found in uninfected cells.

However, it has low bio availability and short half-life, meaning it has to be taken five times per day. If given inpatient, it can crystallize in the kidney (renal tubules).

Resistance

Thymidine kinase can be either altered or removed in mutated HSV. For those cases, Foscarnet is used as a substitute.

Valacyclovir

Works like acyclovir, but a structural difference allows it to be hydrolyzed. For this reason, it has better bioavailability and half-life.

Famciclovir

Prodrug of Penciclovir. Similar bioavailability to acyclovir.

Ganciclovir

Structurally similar to acyclovir, with an additional -CH2OH group. This makes it much more effective against Cytomegalovirus.

It is given IV in the hospital only for its poor bioavailability.

Side effects

The most important is bone marrow suppression leading to neutropenia and thrombocytopenia. There is also risk for renal toxicity (crystallization) and it is teratogenic.

Foscarnet

Used against HSV infection as a last line therapy if there are mutations with Thymidine Kinase. It is an inorganic pyrophosphate analogue which directly inhibits DNA polymerase.

Side effects

Has a very narrow therapeutic index which can result in renal toxicity, electrolyte imbalances, and risk of seizures.

Cidofovir

Nucleotide analogue of cytosine and does not require viral Thymidine kinase. Used to treat resistant Cytomegalovirus.

It has a very long half-life. A weekly induction dose is given, followed by every two weeks for maintenance dosing.

Side effects

Extremely nephrotoxic and will destroy the proximal convoluted tubules of the kidney. Therefore, it is given with Probenecid, which prevents tubular uptake.

Resistance

Can occur by viral point mutations.

UL97: Resistance to ganciclovir and valganciclovir
UL54: Resistance to ganciclovir, cidofovir and foscarnet