Medical use
Aciclovir is used for the treatment of herpes simplex virus (HSV) and varicella zoster virus infections, including:
Genital herpes simplex (treatment and prevention)
Neonatal herpes simplex
Herpes simplex labialis (cold sores)
Shingles
Acute chickenpox in immunocompromised patients
Herpes simplex encephalitis
Acute mucocutaneous HSV infections in immunocompromised patients
Herpes of the eye and herpes simplex blepharitis  (a chronic (long-term) form of herpes eye infection)
Prevention of herpes viruses in immunocompromised people (such as people undergoing cancer chemotherapy)Its effectiveness in treating Epstein–Barr virus (EBV) infections is less clear. It has not been found to be useful for infectious mononucleosis due to EBV. Valaciclovir and acyclovir act by inhibiting viral DNA replication, but as of 2016 there was little evidence that they are effective against Epstein–Barr virus, they are expensive, they risk causing resistance to antiviral agents, and (in 1% to 10% of cases) can cause unpleasant side effects.Aciclovir taken by mouth does not appear to decrease the risk of pain after shingles. In those with herpes of the eye, aciclovir may be more effective and safer than idoxuridine. It is not clear if aciclovir eye drops are more effective than brivudine eye drops.Intravenous aciclovir is effective to treat severe medical conditions caused by different species of the herpes virus family, including severe localized infections of herpes virus, severe genital herpes, chickenpox and herpesviral encephalitis. It is also effective in systemic or traumatic herpes infections, eczema herpeticum and herpesviral meningitis.
Resistance
Resistance to aciclovir is rare in people with healthy immune systems, but is more common (up to 10%) in people with immunodeficiencies on chronic antiviral prophylaxis (transplant recipients, people with acquired immunodeficiency syndrome due to HIV infection). Mechanisms of resistance in HSV include deficient viral thymidine kinase; and mutations to viral thymidine kinase or DNA polymerase, altering substrate sensitivity. Microbiology
Aciclovir is active against most species in the herpesvirus family. In descending order of activity:
Herpes simplex virus type I (HSV-1)
Herpes simplex virus type II (HSV-2)
Varicella zoster virus (VZV)
Epstein–Barr virus (EBV)
Human cytomegalovirus (HCMV)  – least activity

Pharmacokinetics
Aciclovir is poorly water-soluble and has poor oral bioavailability (15–30%), hence intravenous administration is necessary if high concentrations are required. When orally administered, peak plasma concentration occurs after 1–2 hours. According to the Biopharmaceutical Classification System  (BCS),  aciclovir falls  under the BCS Class III drug i.e. soluble with low intestinal permeability. Aciclovir has a high distribution rate; protein binding is reported to range from 9 to 33%. The elimination half-life (t1/2) of aciclovir depends according to age group; neonates have a t1/2 of 4 hours, children 1–12 years have a t1/2 of 2–3 hours whereas adults have a t1/2 of 3 hours. Chemistry
Details of the synthesis of aciclovir were first published by scientists from the University at Buffalo. In the first step shown, 2,6-dichloropurine was alkylated with 1-benzoyloxy-2-chloromethoxyethane.