Reviews of research dating from the 1980s show there is some effect in reducing the number and duration of lesions if aciclovir is applied at an early stage of an outbreak. Research shows effectiveness of topical aciclovir in both the early and late stages of the outbreak as well as improving methodologically and in terms of statistical certainty from previous studies. Aciclovir trials show that this agent has no role in preventing HIV transmission, but it can help slow HIV disease progression in people not taking anti-retroviral therapy (ART). This finding emphasizes the importance of testing simple, inexpensive non-ART strategies, such as aciclovir and cotrimoxazole, in people with HIV. Pregnancy
Classified as a Category B drug, the CDC and others have declared that during severe recurrent or first episodes of genital herpes, aciclovir may be used. For severe HSV infections (especially disseminated HSV), IV aciclovir may also be used. Studies in mice, rabbits and rats (with doses more than 10 times the equivalent of that used in humans) given during organogenesis have failed to demonstrate birth defects. Studies in rats in which they were given the equivalent to 63 times the standard steady-state humans concentrations of the drug on day 10 of gestation showed head and tail anomalies.Aciclovir is recommended by the CDC for treatment of varicella during pregnancy, especially during the second and third trimesters.Aciclovir is excreted in the breast milk, therefore it is recommended that caution should be used in breast-feeding women.
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.