Acyclovir has been used to treat chickenpox in children even though the benefits have not been clearly established. Most experts feel that effective treatment is limited to episodes in which the medication is started after the first day of rash. Concerns about viral resistance have also influenced decisions about acyclovir risk-benefit. Balfour and associates used a randomized, double-blind trial to look at the risks and benefits of treating chickenpox (within 24 hours of rash onset in all age groups) with acyclovir, comparing five days of therapy with seven days of therapy. Viral in vitro resistance was tested after treatment. Participants were divided into two groups. Group A was enrolled within 24 hours of rash onset, and group B was enrolled 24 to 48 hours after rash onset. Patients in group A randomly received acyclovir for seven days or acyclovir for five days followed by two days of placebo. Patients in group B randomly received either five days of acyclovir and two days of placebo (active medication started 24 to 48 hours after rash onset) or placebo for the first day, acyclovir for five days, and placebo on the seventh day (active medication started 48 to 72 hours after onset of rash). The dosage of acyclovir used was 20 mg per kg, with a maximum dosage of 800 mg given orally four times daily. Patients were regularly evaluated for chickenpox for 90 days. Skin lesions from all patients were cultured repeatedly for varicella zoster virus, and the isolates were tested for susceptibility to acyclovir. Other symptoms were also routinely evaluated, as was the intensity of pruritus.

There was no difference in clinical end points between the two populations in group A, both of which received acyclovir for varying periods. A comparison of group A with group B clarified the point that earlier treatment shortened the duration of symptoms. Adverse events, including elevated liver function test results, were mild or moderate, and aspartate aminotransferase levels did not differ between the two groups.

The period of viral shedding was significantly shorter in patients in group A than in those in group B who received five days of acyclovir and two days of placebo, but not significantly so when compared with patients in group B who received placebo for the first day followed by five days of acyclovir, and one additional day of placebo. There was no benefit from the longer seven-day medication course. Earlier treatment also demonstrated quicker cessation of new lesion formation, reduction in fever duration, and more rapid healing. There was no evidence of short-term viral resistance with treatment.

The authors conclude that children, adolescents, and adults with chickenpox have a shorter clinical illness when given acyclovir earlier following onset of rash, preferably within 24 hours. There also appears to be benefit in initiating treatment during the second day of rash when compared with starting on the third day of rash. Five days of treatment are as effective as seven days of treatment. Treatment with acyclovir does not cause short-term viral resistance.