Pharmacotherapeutic group: Direct acting antivirals, Nucleosides and nucleotides excl. reverse transcriptase inhibitors.
ATC code: J05AB01
Aciclovir is a synthetic purine nucleoside analogue with
in vitro
and
in vivo
inhibitory activity against human herpes viruses, including herpes simplex virus (HSV) types I and II and varicella zoster virus (VZV).
The inhibitory activity of aciclovir for HSV I, HSV II and VZV is highly selective. The enzyme thymidine kinase (TK) of normal, uninfected cells does not use aciclovir effectively as a substrate, hence toxicity of mammalian host cells is low; however, TK encoded by HSV and VZV converts aciclovir to aciclovir monophosphate, a nucleoside analogue which is further converted to the diphosphate and finally to the triphosphate by cellular enzymes. Aciclovir triphosphate interferes with the viral DNA polymerase and inhibits viral DNA replication with resultant chain termination following its incorporation into the viral DNA.
Prolonged or repeated courses of aciclovir in severely immuno-compromised individuals may result in the selection of virus strains with reduced sensitivity, which may not respond to continued aciclovir treatment. Most of the clinical isolates with reduced sensitivity have been relatively deficient in viral TK, however, strains with altered viral TK or viral DNA polymerase have also been reported.
In vitro
exposure of HSV isolates to aciclovir can also lead to the emergence of less sensitive strains. The relationship between the
in vitro
-determined sensitivity of HSV isolates and clinical response to Aciclovir therapy is not clear.
