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. Treatment of herpes simplex gingivostomatitis with aciclovir in children: a randomised double blind placebo controlled study. Oral acyclovir in the treatment of herpes zoster in general practice. Efficacy of oral acyclovir treatment of acute herpes zoster. Oral acyclovir for prevention of herpes simplex virus reactivation after marrow transplantation. A randomised placebo controlled trial of suppressive acyclovir in late pregnancy in women with recurrent genital herpes infection. Oral acyclovir therapy for mucocutaneous herpes simplex virus infections in immunocompromised marrow transplant recipients.
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. To examine the efficacy of aciclovir suspension for treating herpetic gingivostomatitis in young children.
                Randomised double blind placebo controlled study.
                Day care unit of a tertiary paediatric hospital.
                72 children aged 1-6 years with clinical manifestations of gingivostomatitis lasting less than 72 hours; 61 children with cultures positive for herpes simplex virus finished the study.
                Duration of oral lesions, fever, eating and drinking difficulties, and viral shedding.
                Aciclovir suspension 15 mg/kg five times a day for seven days, or placebo.
                Children receiving aciclovir had oral lesions for a shorter period than children receiving placebo (median 4 v 10 days (difference 6 days, 95% confidence interval 4.0 to 8.0)) and earlier disappearance of the following signs and symptoms: fever (1 v 3 days (2 days, 0.8 to 3.2)); extraoral lesions (lesions around the mouth but outside the oral cavity) (0 v 5.5 days (5.5 days, 1.3 to 4.7)); eating difficulties (4 v 7 days (3 days, 1.31 to 4.69)); and drinking difficulties (3 v 6 days (3 days, 1.1 to 4.9)). Viral shedding was significantly shorter in the group treated with aciclovir (1 v 5 days (4 days, 2.9 to 5.1)).
                Oral aciclovir treatment for herpetic gingivostomatitis, started within the first three days of onset, shortens the duration of all clinical manifestations and the infectivity of affected children. Further studies are needed to evaluate the ideal dose and length of treatment. A double-blind, randomised trial evaluated the efficacy of oral acyclovir, 800 mg 5 times daily for 7 days, in acute herpes zoster and postherpetic neuralgia. Forty patients aged 16 years or over, presenting to their general practitioners within 3 days of rash onset, received acyclovir, while 43 patients received placebo. Acyclovir reduced the extent and duration of the rash, the spread of the rash to adjacent dermatomes and the incidence of disseminated lesions. It shortened the period of new lesion formation and reduced the incidence of ulceration. The weekly prevalence of pain was reduced on acyclovir by the fourth week, with a reduction in the monthly prevalence of chronic pain in the second and third months and a reduction in associated local neurological symptoms between months 3-6. Total analgesic use in the first 4 weeks was reduced by acyclovir, but during follow up there was no difference in the prevalence of analgesic use between groups. There were slightly fewer medical events on acyclovir in the second week, but the frequency was the same in each group for the rest of the 6 months. Biochemical and haematological tests showed no adverse effects of treatment. Oral acyclovir, 800 mg five times per day for seven days, was compared with placebo in a randomized, double-blind trial conducted at three centers in the United Kingdom. The study group consisted of 364 elderly immunocompetent patients with herpes zoster who were entered within 72 hours of the onset of rash. Acyclovir significantly reduced the times to last new lesion formation (p less than 0.01), loss of vesicles (p less than 0.01), and full crusting (p = 0.03). No significant hastening of rash healing was seen in those who started therapy later than 48 hours after the onset of rash. There was also a significant reduction pain during treatment with acyclovir (p = 0.02). Acyclovir produced no effects on the frequency or severity of post-herpetic neuralgia. No clinically important adverse effects of acyclovir were reported. Oral acyclovir was found to be safe and effective for the prevention of herpes simplex virus reactivation after marrow transplantation in a double-blind, placebo-controlled trial. Acyclovir or placebo was administered to 49 patients for 5 weeks beginning 1 week before transplantation: 5 of 24 patients receiving acyclovir developed herpes simplex virus infection during prophylaxis, compared to 17 of 25 patients receiving placebo (p less than 0.01). The median time to first virus reactivation was significantly longer among patients receiving acyclovir (78 days versus 9 days after transplant, p = 0.006). The effect was even more pronounced when the analysis was adjusted for drug compliance: Among patients taking a minimum of 40% of their prescribed drug, acyclovir was 96% virologically effective and 100% clinically effective during the period of administration. Acyclovir use was also associated with significantly more rapid marrow engraftment in patients receiving methotrexate. No virus resistant to acyclovir was isolated. Oral acyclovir provides effective prophylaxis against reactivation of herpes simplex virus among severely immunosuppressed patients able to take orally administered drugs. To evaluate the efficacy and safety of a suppressive course of acyclovir in late pregnancy in women with recurrent genital herpes infection on the incidence of viral shedding, herpes lesion development and caesarean section for recurrent genital herpes.
                Double-blind, randomised placebo controlled clinical trial.
                A department of genitourinary medicine in Sheffield and an antenatal clinic in London.
                Pregnant women with recurrent genital herpes infection at < 36 weeks of gestation.
                Participating women were given acyclovir 200 mg four times a day (or matching placebo) from 36 weeks of gestation until the time of delivery. Women were seen weekly and viral cultures were obtained from the cervix and vulva. Decisions regarding mode of delivery were left to the discretion of the attending obstetrician.
                Delivery by caesarean section for recurrent genital herpes infection. Number of episodes of recurrent genital herpes infection and number of episodes of asymptomatic viral shedding during the treatment period. In addition blood was taken at two weekly intervals to determine acyclovir levels.
                The total number of women recruited was 63 (31 received acyclovir and 32 received placebo). The number of women undergoing delivery by caesarean section for recurrent herpes at the time of delivery was 12 (19%). The odds ratio for delivery by caesarean section in women taking acyclovir, compared with those taking placebo, was 0.44 (95% CI 0.09-1.59). The odds ratio for clinical recurrences during treatment was 0.10 (95% confidence interval 0.00-0.86) and the odds ratio for clinical recurrence or asymptomatic shedding during treatment was 0.32 (95% CI 0.05-1.56).
                This trial was unable to demonstrate that acyclovir can significantly decrease the number of caesarean section deliveries; however, the number of clinical recurrences was significantly reduced. Two episodes of asymptomatic virus shedding both occurred in women taking acyclovir. At the present time there is little evidence to suggest that acyclovir should be used outside randomised controlled trials for the suppression of recurrent genital herpes infection during pregnancy. In a randomized, double-blinded, placebo-controlled trial, we compared the therapeutic effect of oral acyclovir (400 mg five times daily for 10 days) with that of placebo in patients with marrow transplants and culture-proven recurrent mucocutaneous herpes simplex. Twelve patients received acyclovir and nine received placebo. Acyclovir treatment significantly shortened the median duration of viral shedding, new lesion formation, and time to first decrease in pain, resolution of pain, 50% healing, and total healing. These results compared favorably with those previously obtained with intravenous or topical acyclovir preparations. Oral acyclovir is highly effective for the treatment of recurrent mucocutaneous infections caused by herpes simplex virus in immunocompromised patients.
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.