A controlled trial of acyclovir for chickenpox in normal children. Acyclovir treatment of varicella in otherwise healthy children. Acyclovir treatment of varicella in otherwise healthy adolescents. The Collaborative Acyclovir Varicella Study Group.
Chickenpox, the primary infection caused by the varicella-zoster virus, affects more than 3 million children a year in the United States. Although usually self-limited, chickenpox can cause prolonged discomfort and is associated with infrequent but serious complications.
                To evaluate the effectiveness of acyclovir for the treatment of chickenpox, we conducted a multicenter, double-blind, placebo-controlled study involving 815 healthy children 2 to 12 years old who contracted chickenpox. Treatment with acyclovir was begun within the first 24 hours of rash and was administered by the oral route in a dose of 20 mg per kilogram of body weight four times daily for five days.
                The children treated with acyclovir had fewer varicella lesions than those given placebo (mean number, 294 vs 347; P less than 0.001), and a smaller proportion of them had more than 500 lesions (21 percent, as compared with 38 percent with placebo; P less than 0.001). In over 95 percent of the recipients of acyclovir no new lesions formed after day 3, whereas new lesions were forming in 20 percent of the placebo recipients on day 6 or later. The recipients of acyclovir also had accelerated progression to the crusted and healed stages, less itching, and fewer residual lesions after 28 days. In the children treated with acyclovir the duration of fever and constitutional symptoms was limited to three to four days, whereas in 20 percent of the children given placebo illness lasted more than four days. There was no significant difference between groups in the distribution of 11 disease complications (10 bacterial skin infections and 1 case of transient cerebellar ataxia). Acyclovir was well tolerated, and there was no significant difference between groups in the titers of antibodies against varicella-zoster virus.
                Acyclovir is a safe treatment that reduces the duration and severity of chickenpox in normal children when therapy is initiated during the first 24 hours of rash. Whether treatment with acyclovir can reduce the rare, serious complications of chickenpox remains uncertain. To determine whether acyclovir administered orally affects the duration and severity of varicella in otherwise normal children.
                Randomized, placebo-controlled, double-blind trial.
                Patients' residence and university hospital clinic.
                One hundred five children between 5 and 16 years of age with laboratory-confirmed varicella entered the study. Of the 102 who were included in the final analysis, 50 received acyclovir and 52 received placebo.
                Placebo or acyclovir was given orally four times daily, for 5 to 7 days. The acyclovir dose was adjusted as follows: 5 to 7 years of age, 20 mg/kg; 7 to 12 years, 15 mg/kg; and 12 to 16 years, 10 mg/kg. MEASUREMENTS and
                Acyclovir recipients, compared with the placebo group, defervesced sooner (median, 1 day vs 2 days; p = 0.001), experienced onset of cutaneous healing sooner, as reflected by a decrease in number of lesions (median, 3 days vs 2 days; p = 0.002), and had fewer skin lesions (median, 500 vs 336; p = 0.02). Acyclovir did not significantly change the rate of complications of varicella (10% in the acyclovir group vs 13.5% among placebo subjects). Adverse drug effects were not observed. Acyclovir recipients had lower geometric mean serum antibody titers to varicella-zoster virus than their placebo counterparts 4 weeks after the onset of illness, but antibody titers in both groups were similar 1 year later.
                These results provide evidence that acyclovir is useful and well tolerated for treatment of varicella in otherwise healthy children. To determine whether orally administered acyclovir is of therapeutic benefit for varicella in otherwise healthy adolescents, and to compare the severity of the disease in adolescents with that in younger children.
                Multicenter, randomized, placebo-controlled, double-blind trial.
                Patients' homes and university hospital clinics.
                Sixty-eight adolescents between 13 and 18 years of age with varicella entered the study. Of the 62 adolescents with laboratory-confirmed varicella who were included in the final analysis, 31 received acyclovir and 31 received placebo.
                Placebo or an 800 mg acyclovir tablet was given orally four times daily for 5 days, beginning within 24 hours of onset of rash.
                Acyclovir recipients had significant reductions in times to cessation of new lesion formation (p less than 0.001), maximum number of lesions (p = 0.019), and defervescence (p = 0.045). Mean constitutional illness score was significantly reduced on day 4 (0.5 vs 1.5, p = 0.05), as was the mean number of residual hypopigmented lesions present on 28-day follow-up examination (22.7 vs 92.7, p = 0.018). Two complications, both bacterial superinfections, occurred in placebo recipients. Adverse experiences and varicella-zoster virus antibody titers measured 28 days after enrollment were similar in both treatment groups. Comparison of placebo recipients with children 2 to 12 years of age participating in a companion study indicated that varicella is more severe in adolescents: mean maximum total lesions (421 vs 347, p = 0.003), mean maximum constitutional illness score (3.1 vs 2.2, p = 0.032), and mean number of residual lesions (92.7 vs 33.2, p = 0.01) were all greater in the adolescent population.
                Oral acyclovir therapy is safe and effective for treatment of varicella in otherwise healthy adolescents; this may be an appropriate subgroup for treatment with antiviral drugs because the disease is more severe in them than in younger children.
Acyclovir appears to be effective in reducing the number of days with fever and the maximum number of lesions among otherwise healthy children with chickenpox. The results were less convincing with respect to the number of days to no new lesions and relief of itchiness. The clinical importance of acyclovir treatment in otherwise healthy children remains uncertain.