Double-blind placebo-controlled trial of oral acyclovir in first-episode genital herpes simplex virus infection

One hundred nineteen patients with primary and 31 patients with nonprimary first-episode genital herpes were treated for ten days with 200 mg of acyclovir capsules or placebo capsules orally five times daily. Among acyclovir recipients with primary genital herpes, the median duration of viral shedding (two days), time to crusting of all lesions (seven days), time to healing of all lesions (12 days), and duration of local pain (five days) and constitutional symptoms (three days) were shorter than among placebo recipients (9, 10, 16, 7, and 6 days, respectively). Among patients with nonprimary first-episode genital herpes, oral acyclovir shortened the median duration of viral shedding but had no significant effect on the duration of lesions or symptoms. The time to first recurrence and frequency of recurrences were similar in acyclovir- and placebo-treated patients. Oral acyclovir treatment of primary first-episode genital herpes shortens the duration of viral shedding and symptoms and accelerates healing, but it does not appear to influence subsequent genital recurrences.     

Acyclovir prophylaxis against herpes virus infections in severely immunocompromised patients: randomised double blind trial

Twenty patients undergoing allogeneic bone marrow transplantation and 39 patients receiving remission induction chemotherapy for acute leukaemia were entered into a double blind, placebo controlled stratified trial of acyclovir prophylaxis against herpes group virus infections. Within the transplant group intravenous acyclovir 5 mg/kg twice daily given throughout the period of granulocytopenia completely prevented oropharyngeal herpes simplex virus infection compared with a 50% incidence in the placebo arm (p = 0.033). The acyclovir group also had fewer days of fever during the trial and a shorter duration of leukopenia, possibly because of the prevention of herpes simplex virus infections. There was a high incidence of herpes infections after the trial in patients who received either acyclovir or placebo. In the non-transplant group there was also a significant reduction of herpes simplex virus infection in the oropharynx and oesophagus (two out of 19 patients as compared with 10 out of 20; p = 0.018). Herpes simplex virus was isolated in the acyclovir arm within a day after starting the trial in one patient, and the other failure was due to a virus with reduced sensitivity to acyclovir in a patient who had had several previous courses of the drug. The incidence of herpes infections after stopping treatment was low. The influence of acyclovir on excretion of Epstein-Barr virus in saliva in either group was inconclusive. One patient (transplant group) developed a cytomegalovirus infection while receiving acyclovir. Acyclovir provides effective prophylaxis against oropharyngeal and oesophageal herpes simplex virus infection in severely immunocompromised seropositive (greater than or equal to 1/8) patients. In patients given bone marrow transplants this may have the additional benefit of reducing the time to recovery of an adequate blood count and the number of days of fever.     

Long-term acyclovir suppression of frequently recurring genital herpes simplex virus infection. A multicenter double-blind trial

Normal adults with six or more episodes of genital herpes in the previous year were enrolled in a one-year, multicenter, double-blind trial comparing placebo with 400 mg of acyclovir administered orally twice daily. Patients with episodes during the study were offered 200 mg of acyclovir administered orally five times daily for five days; this allowed comparison of suppressive and episodic treatment. After one year, 227 (44%) of 519 patients receiving suppressive treatment and seven (2%) of 431 receiving placebo (episodic) treatment remained free of recurrences, and the mean numbers of recurrences per year were 1.8 and 11.4, respectively. Among 67 patients who had received suppressive therapy for one year, the mean duration of lesions in the first episode following the discontinuation of treatment was 9.3 days compared with 7.3 days among 45 patients who had received episodic therapy for one year. Treatment was well tolerated, and no changes were noted in the in vitro susceptibility to acyclovir of herpes simplex virus cultured during or after the one-year trial. Continuous or episodic oral acyclovir therapy for one year remained safe and effective.     

Failure of acyclovir cream in treatment of recurrent herpes labialis

A double blind, randomised, crossover placebo controlled trial of 5% acyclovir cream, applied topically five times a day for five days, was carried out in 45 patients with recurrent herpes labialis. These patients had a total of 72 episodes, 34 of which were treated with the 5% acyclovir cream and 38 with placebo cream. Treatment was begun by the patients as soon as possible after the onset of prodromal symptoms. There was no significant clinical benefit from treatment with acyclovir cream compared with placebo cream. The median healing times were nine days with acyclovir cream, 10 days with placebo cream, and 13 days when no treatment was given. The possibility that the 40% propylene glycol cream base alone has a therapeutic effect must therefore be considered.     

Successful treatment of herpes labialis with topical acyclovir

A double blind, placebo controlled trial of 5% acyclovir cream, applied topically five times a day for five days, was carried out in 49 patients with recurrent herpes labialis. These patients had a total of 74 episodes, 34 of which were treated with the 5% acyclovir cream and 40 with matching placebo. First episodes and all episodes treated with acyclovir cream had significantly shorter times to formation of ulcer or crust and to complete healing (p less than 0.05 for all variables). The duration of all symptoms and proportion of patients developing itching was also reduced by acyclovir cream in first episodes, though the difference was not significant. When the patient started treatment early in the course of a first episode acyclovir cream significantly reduced the percentage of lesions progressing beyond the papular stage (p less than 0.05). Acyclovir cream is well tolerated and effective for the treatment of recurrent herpes labialis.     

Recombinant glycoprotein vaccine for the prevention of genital HSV-2 infection: two randomized controlled trials. Chiron HSV Vaccine Study Group.

CONTEXT: In the last 3 decades, herpes simplex virus type 2 (HSV-2) infection seroprevalence and neonatal herpes have increased substantially. An effective vaccine for the prevention of genital herpes could help control this epidemic. OBJECTIVE: To evaluate the efficacy of a vaccine for prevention of HSV-2 infection. DESIGN: Two randomized, double-blind, placebo-controlled multicenter trials of a recombinant subunit vaccine containing 30 microg each of 2 major HSV-2 surface glycoproteins (gB2 and gD2) against which neutralizing antibodies are directed, administered at months 0, 1, and 6. Control subjects were given a citrate buffer vehicle. Participants were followed up for 1 year after the third immunization. SETTING AND PARTICIPANTS: We enrolled 2393 persons from December 10, 1993, to April 4, 1995, who were HSV-2 and human immunodeficiency virus seronegative. One trial with 18 centers enrolled 531 HSV-2-seronegative partners of HSV-2-infected persons; the other, with 22 centers, enrolled 1862 persons attending sexually transmitted disease clinics. A total of 2268 (94.8%) met inclusion criteria and were included in the analysis with 1135 randomized to placebo and 2012 to vaccine. MAIN OUTCOME MEASURE: Time to acquisition of HSV-2 infection, defined by seroconversion or isolation of HSV-2 in culture during the study period by randomization group. RESULTS: Time-to-event curves indicated a 50% lower acquisition rate among vaccine vs placebo recipients during the initial 5 months of the trial; however, overall vaccine efficacy was 9% (95% confidence interval, -29% to 36%). Acquisition rates of HSV-2 were 4.6 and 4.2 per 100 patient-years in the placebo and vaccine recipients, respectively (P =.58). Follow-up of vaccine recipients acquiring HSV-2 infection showed vaccination had no significant influence on duration of clinical first genital HSV-2 episodes (vaccine, median of 7.1 days; placebo, 6.5 days; P>.10) or subsequent frequency of reactivation (median monthly recurrence rate with vaccine, 0.2; with placebo, 0.3; P>.10). The vaccine induced high levels of HSV-2-specific neutralizing antibodies in vaccinated persons who did and did not develop genital herpes. CONCLUSIONS: Efficient and sustained protection from sexual acquisition of HSV-2 infection will require more than high titers of specific neutralizing antibodies. Protection against sexually transmitted viruses involving exposure over a prolonged period will require a higher degree of vaccine efficacy than that achieved in this study.     

Acyclovir for the treatment and prevention of recurrent infectious herpes simplex keratitis

目的　观察无环鸟苷对HSV 1角膜炎的治疗和预防复发作用。方法　选用 1 0 5例HSV角膜炎病人 ,将病人按临床表现分为 4组 ,即上皮型、基质型、坏死型及HSV角膜炎行角膜移植及结膜瓣遮盖术 ,并对 4组病人选用全身 +局部无环鸟苷治疗。愈后将上皮质型和基质型患者随机分为2组 ,抗复发治疗组和对照组。治疗组给予口服预防量无环鸟苷 3 0 0mg/d ,持续一年。对照组未给予任何药物。结果　上皮型经口服及局部点眼后 96%痊愈。基质型给予口服加局部无环鸟苷点眼 ,同时给予激素滴眼治愈率为 1 0 0 %。坏死型经 1 0 0 0mg/d无环鸟苷静脉应用 ,治愈率达 3 3 % ,余穿孔行结膜瓣遮盖及角膜移植术 ,术后静脉应用无环鸟苷 2周尽快控制病情 ,角膜植片及结膜与伤口愈合。上皮质型和基质型的角膜炎治愈后持续应用无环鸟苷口服 3 0 0mg/d ,随访 1年 ,治疗组有 5例复发 ,对照组有 1 4例复发 ,两组比较有显著的统计学差 (P <0 0 1 )。结论　无环鸟苷局部 +全身治疗对HSV角膜炎有较好的治疗作用 ,低剂量长期口服对控制复发有良好的作用。随访期间未见全身及局部副作用     

Treatment of resistant herpes simplex virus with continuous-infusion acyclovir

Two patients with acquired immunodeficiency syndrome who developed severe ulcerative proctitis caused by herpes simplex virus type 2 that was resistant to acyclovir were successfully treated with 6 weeks of high-dose, continuous-infusion acyclovir sodium (1.5 to 2.0 mg/kg per hour). Viruses cultured from the lesions were resistant to acyclovir in vitro after the patients had received prolonged therapy with oral and intravenous acyclovir in traditional divided doses. Investigation into the mechanism of the acyclovir resistance revealed changes in the thymidine-kinase activity of both isolates. This viral enzyme phosphorylates acyclovir and is necessary for drug activation. The first patient's isolate was deficient of all thymidine-kinase activity, while the second patient's isolate had a thymidine kinase with altered substrate specificity for acyclovir. The continuous infusion was safe, well tolerated, and done in an outpatient setting with weekly clinic visits and monitoring of creatinine and acyclovir levels.     

Topical ether and herpes simplex labialis

In a double-blind, placebo-controlled study, 51 patients with recurrent herpes simplex labialis were treated with topical ether or placebo within 24 hours of onset of a lesion. There was no noteworthy difference between groups given ether and placebo in progression of lesions, healing time, duration or intensity of pain, and duration or quantity of virus excretion. The ether also failed to reduce appreciably lesion virus titer, even when lesions were cultured immediately after topical application. Despite these results, 75% of the patients receiving ether and 77% of those receiving placebo reported effective reduction of the severity and duration of lesions. The marked placebo effect in the treatment of recurrent herpes infection helps to emphasize the need for objective measurements and placebo-controlled studies.     

Herpes simplex encephalitis in infants

Two cases are reported of severe encephalitis in infants that were caused by a primary infection with herpes simplex virus type 1. Both patients presented with focal seizures; the clinical diagnosis was confirmed by the rapid appearance of IgM antibody to herpes simplex virus type 1 in cerebrospinal fluid and serum. In spite of the early use of acyclovir, which was administered by the intravenous route, the clinical response was poor and both infants were left with severe neurological impairment.     

The role of oral acyclovir in the management of genital herpes simplex.

Oral acyclovir is an antiviral nucleoside analogue that has recently been released in Canada for use in selected patients with genital infections by the herpes simplex virus. First episodes of genital herpes should be treated with oral acyclovir as soon as the diagnosis is considered. Most people with recurrent genital herpes do not require systemic drug therapy. Selected patients with severe or long-lasting recurrences, recurrences associated with long prodromal periods (greater than 12 to 24 hours) or systemic complications such as erythema multiforme and eczema herpeticum may receive measurable benefit from treatment at the onset of symptoms. In most patients frequently recurrent disease can be suppressed with long-term therapy. Since long-term safety beyond 1 year has not been established, suppressive therapy should be stopped at least once per year to reassess the recurrence pattern. Acyclovir has not been adequately tested for safety in pregnancy and should not be prescribed for pregnant women unless the potential benefits outweigh the risks. Careful attention to disease severity, accurate diagnosis and exclusion of other causes of genital lesions will ensure that the drug is used only when beneficial.     

奈尔斯全身红光治疗系统对治疗单纯疱疹临床疗效观察

目的观察奈尔斯全身红光治疗系统对治疗单纯疱疹的治疗效果。方法对31例单纯疱疹患者进行全身红光照射并常规口服阿昔洛韦800mg/d与单纯疱疹患者20例（采用常规治疗）相对照,比较治疗前后病灶愈合情况。结果疗效：31例患者中痊愈29例（93.5%）,显效1例（3.2%）,有效1例（3.2%）,无效0例（0%）,总痊愈有效率为96.7%。结论奈尔斯全身红光治疗系统对单纯疱疹具有操作简单,安全无副作用,能改善单纯疱疹的自觉症状,延长复发时间有效改善患者的生活质量,是一种值得推广的理疗方法。     

Relapse of herpes simplex encephalitis after conventional acyclovir therapy

Acyclovir sodium is the drug of choice for the treatment of herpes simplex encephalitis. We treated an immunocompetent patient with a ten-day course of intravenous acyclovir sodium at the recommended dosage of 10 mg/kg every eight hours for clinically apparent herpes simplex encephalitis. After marked improvement, his condition deteriorated four days after completing acyclovir therapy. A subsequent brain biopsy specimen disclosed acyclovir-sensitive herpes simplex virus type 1. A longer duration of acyclovir therapy (14 to 21 days) should be considered for treating herpes simplex encephalitis.     

Frequency of asymptomatic shedding of herpes simplex virus in women with genital herpes

Twenty-seven women with recurrent genital herpes simplex virus infection underwent daily home culturing to detect asymptomatic genital herpes simplex virus shedding. Asymptomatic herpes simplex virus shedding was documented on 1% of the days on which cultures were obtained. Asymptomatic shedding from the vulva was as frequent as asymptomatic cervicovaginal shedding, and 45% of asymptomatic episodes were identified only by positive results from vulvar cultures. All women who obtained samples on more than 100 days and 80% of women who obtained samples on more than 50 days had documented asymptomatic viral shedding, compared with only 6% of those who obtained samples for fewer than 25 days. Asymptomatic shedding was not related to contraceptive use or menstrual cycle. These data suggest that all women with recurrent genital herpes simplex virus infection should be instructed about the possible risk, albeit infrequent, of asymptomatically shedding virus from the genital tract.     

Acyclovir treatment of herpes simplex encephalitis: experience in a district hospital

Herpes simplex encephalitis may be underdiagnosed in Britain. We report eight patients treated at one hospital over three years. Fever, impaired consciousness or focal neurological signs were seen in all patients at presentation but herpes simplex encephalitis was rarely considered as the initial diagnosis. The electroencephalogram was the only initial investigation that was abnormal in each case and was the most useful test in establishing a clinical diagnosis. The diagnosis was confirmed by laboratory methods in each case. Following acyclovir treatment five patients were able to resume normal activities, one patient has moderate disability and two patients died. Three patients showed clinical evidence of relapse but two improved after further treatment with acyclovir. Herpes simplex encephalitis is a treatable condition and should be considered in all patients presenting with fever and neurological signs. The electroencephalogram is usually abnormal and the changes may be characteristic of the condition.     

阿昔洛韦软膏联合聚维酮碘软膏治疗带状疱疹皮损的疗效观察

目的：带状疱疹是由水痘一带状疱疹病毒引起的急性炎症性皮肤病,局部皮损的治疗影响带状疱疹的转归。本研究观察阿昔洛韦软膏联合聚维酮碘软膏治疗带状疱疹病毒感染后表现为单侧发疹、成簇水疱皮损的疗效。方法：我科2003年5月至2008年6月75例入选住院病人随机分为三组：A组,阿昔洛韦软膏治疗组（n=25）;B组,聚维酮碘软膏治疗组（n=25）;C组,联合治疗组（n=25）。三组患者均予阿昔洛韦每8小时0．5g静脉滴注,皮损均局部消毒后分别单用阿昔洛韦软膏、单用聚维酮碘软膏及联合阿昔洛韦软膏、聚雏酮碘软膏外涂患处,之后覆盖无菌纱布,每天换药一次。观察3d、5d和7d后皮损变化情况。结果：联合用药3d、5d和7d后皮损的痊愈率和总有效率均优于单用阿昔洛韦软膏或聚维酮碘软膏（P＜0．05）,并发感染率也明显降低（P＜0．05）。结论：阿昔洛韦软膏联合聚维酮碘软膏能更有效治疗带状疱疹局部皮损,早期即可取得较好的效果,具有更好的疗效和抗感染作用。     

HLA-DRw6 as a risk factor for active cytomegalovirus but not for herpes simplex virus infection after renal allograft transplantation

To study genetically determined susceptibility to cytomegalovirus and herpes simplex virus infections in patients given renal transplants a prospective study was performed of 68 consecutive patients receiving their first cadaveric kidney allograft. The recipients positive for HLA-DRw6 showed a significantly increased incidence of active cytomegalovirus infection as early as the 10th week after transplantation (p less than 0.05). No relation with other human leucocyte antigens was found, nor did a correlation exist between HLA typing and the incidence of herpes simplex virus infections. Furthermore, recipients positive for HLA-DRw6 with secondary cytomegalovirus infections excreted infectious virus more often (p less than 0.01) and showed more clinical symptoms (p less than 0.01) than a comparable group of recipients negative for HLA-DRw6. These observations may have practical implications for the treatment of patients who have had renal transplant operations.     

Disseminated herpes simplex virus infection in an apparently immunocompetent woman

A young, previously healthy woman developed bilateral exudative tonsillitis that was associated with severe systemic symptoms. This was followed by evidence of multisystem disease with acute abdominal pain, raised liver enzyme levels, respiratory difficulty, increasing drowsiness and multiple vesicular skin lesions. Herpes simplex virus type-1 was isolated from skin lesions and a throat swab and herpes simplex virus type-1 antigen was detected in a liver biopsy sample. She recovered rapidly without any sequelae after treatment with intravenously administered acyclovir.     

口腔单纯疱疹患者血清中IgE、IgM、IgA水平变化

目的：研究口腔单纯疱疹患者血清中IgE、IgM、IgA水平变化及临床疗效观察。方法：对60例患者治疗前后进行静脉采血,采用ELASA法检测观察指标。结果：治疗组治疗前血清中IgE、IgM、IgA水平均显著高于对照组及治疗后水平。结论：阿昔洛韦＋维生素B1＋胸腺肽胶囊治疗口腔单纯疱疹患者有显著疗效,且对血清中IgE、IgM、IgA水平有影响。     

中西医结合治疗单纯疱疹病毒性角膜炎58例

目的 观察增损银翘散联合无环鸟苷治疗单纯疱疹病毒性角膜炎（上皮型）的临床疗效。方法 115例患者分组，治疗组58例62只眼，对照组57例61只眼。对照纽予以0．1％无环鸟苷滴眼液点眼，口服阿昔洛韦片；治疗组在对照组疗法的基础上虽用增损银翘散煎服，同时给予清开灵静脉滴注。结果 治疗组治愈率和总有效率分别为87．10％和96．77％，对照纽的治愈率和总有效率为67，21％和91．80％，两组相比总有效率有显著性差异（P〈0．05），治愈率有非常显著差异（P〈0．01）；治愈天数两组相比差异显著（P〈0．05）。结论 对于单纯疱疹病毒性角膜炎采用中西医结合疗法效果更好，临床治愈率高，见效快，复发率低。