Treatment of herpes simplex gingivostomatitis with aciclovir in children: a randomised double blind placebo controlled study. Acyclovir given as prophylaxis against oral ulcers in acute myeloid leukaemia: randomised, double blind, placebo controlled trial. Oral acyclovir in the treatment of herpes zoster in general practice. Efficacy of oral acyclovir treatment of acute herpes zoster. Acyclovir treatment of varicella in otherwise healthy adolescents. The Collaborative Acyclovir Varicella Study Group. A randomised placebo controlled trial of suppressive acyclovir in late pregnancy in women with recurrent genital herpes infection. Oral acyclovir in herpes zoster ophthalmicus. Effect of acyclovir on radiation- and chemotherapy-induced mouth lesions. A controlled trial of acyclovir for chickenpox in normal 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. To evaluate (a) the prophylactic effect of the antiherpetic drug acyclovir on oral ulcers in patients with acute myeloid leukaemia receiving remission induction chemotherapy and thus (b), indirectly, the role of herpes simplex virus in the aetiology of these ulcers.
                Randomised, double blind, placebo controlled trial.
                74 herpes simplex virus seropositive patients aged 18-84. Thirty seven patients received acyclovir (800 mg by mouth daily) and 37 placebo. The patients were examined daily for 28 days.
                Occurrence of herpes labialis, intraoral ulcers, and acute necrotising ulcerative gingivitis.
                The two populations were comparable in age, sex, type of antineoplastic treatment, and history of herpes labialis. Acute oral infections occurred in 25 of the acyclovir treated patients and 36 of the placebo treated patients (relative risk 0.69 (95% confidence interval 0.55 to 0.87)). This difference was due to a reduction in the incidence of herpes labialis (one case versus eight cases; relative risk 0.13 (0.02 to 0.95)), intraoral ulcers excluding the soft palate (one case versus 13 cases; relative risk 0.08 (0.01 to 0.56)), and acute necrotising ulcerative gingivitis (one case versus eight cases; relative risk 0.13 (0.02 to 0.95)). However, ulcers on the soft palate were diagnosed with similar frequency in the two groups. Isolation of herpes simplex virus type 1 in saliva was reduced from 15 cases in the placebo group to one case in the acyclovir group (relative risk 0.07 (0.01 to 0.48)).
                Intraoral ulcers excluding the soft palate are most often due to infection with herpes simplex virus, whereas ulcers on the soft palate have a non-herpetic aetiology. The findings suggest that acute necrotising ulcerative gingivitis may also be due to herpes simplex virus. Prophylaxis with acyclovir should be considered for patients with acute myeloid leukaemia during remission induction therapy. 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. 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 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. 46 patients with acute herpes zoster ophthalmicus of less than 72 hours duration were recruited into a placebo controlled trial to assess the efficacy of oral acyclovir, 800 mg 5 times daily, in preventing or modifying ocular complications and pain. Fewer acyclovir recipients developed intraocular complications and these were less severe but neither difference was statistically significant. However, active ocular disease was significantly less common in the acyclovir group (p = 0.01) at 6 months. Pain was significantly less severe in the acyclovir group between 2 and 6 months. The proportion of patients with pain scores greater than 0 was significantly lower in the acyclovir group between 2 and 3 months. Oral acyclovir appears to modify the disease process in herpes zoster ophthalmicus, to reduce the severity and incidence of postherpetic pain and especially to protect against long-term ocular complications. Several chemotherapeutic regimens and radiation therapy, if delivered to the oral mucosa, are associated with a high frequency of mouth lesions. The cause of this side effect is not known for certain, but in past studies it has sometimes been associated with the ability to culture herpes simplex virus type 1 from the mouth. In a double-blind prospective trial, patients with head and neck tumors treated with chemotherapy or radiation therapy were treated with either acyclovir or placebo. Although the frequency of culture-positive herpes simplex virus was low in the untreated group, it was significantly lower, zero, in the acyclovir-treated group. However, there were no differences in the frequency or type of mouth lesions experienced by patients receiving either radiation or chemotherapy who were taking acyclovir or placebo. These results suggest that herpes simplex virus is not a frequent cause or complication of oral lesions afflicting this patient population. 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.
We found two relevant trials in this systematic review, only one of them could provide some weak evidence that acyclovir is an effective treatment in reducing the number of oral lesions, preventing the development of new extraoral lesions, decreasing the number of individuals with difficulties experienced in eating and drinking and reducing hospital admission for children under 6 years of age with primary herpetic gingivostomatitis.