Famciclovir for the treatment of recurrent genital and labial herpes lesions

Famciclovir (Famvir, Novartis) is an effective treatment for herpes zoster and herpes simplex. Two separate studies recently examined the effectiveness of single high doses of famciclovir for treating recurrent genital herpes and labial herpes (cold sores). In the randomized, placebo-controlled studies, patients initiated treatment at the first onset of symptoms. For the treatment of genital herpes, a 1,000 mg b.i.d. dose of famciclovir had significant advantages over the placebo, reducing the time required to heal the lesions, preventing the development of lesions beyond the papule stage, and improving the time to resolution of all symptoms. For the treatment of labial herpes, a single 1,500 mg dose of famciclovir shortened the lesion healing time, shortened the time to normal skin, and resulted in faster resolution of pain and tenderness.     

Topical alpha-interferon in recurrent genital herpes simplex infection. A double-blind, placebo-controlled clinical trial

We conducted a double-blind placebo-controlled clinical trial on 98 subjects to assess the efficacy of two strengths of topical human leukocyte alpha-interferon, 10(4) and 10(6) IU/g in a 1% nonoxynol-9 base, in the treatment of recurrent genital herpes simplex virus (HSV). The study medication was applied during the prodromal phase or at the first sign of recurrence of the infection. The high-dose alpha-interferon was found to be significantly more effective than the low-dose interferon and placebo with respect to the duration of viral shedding as well as in reducing the time to the end of all subjective symptoms, including pain, burning and itching. No difference between the three groups was found in times to crusting or healing. Further studies of topical interferon in the treatment of HSV and other viral infections are merited.     

Acyclovir vs isoprinosine (immunovir) for suppression of recurrent genital herpes simplex infection.

OBJECTIVE--To compare the efficacy and safety of oral acyclovir (400 mg twice daily) with oral isoprinosine (500 mg twice daily) in the suppression of recurrent genital herpes. DESIGN--Double-blind, double-dummy, randomised, controlled, parallel group trial. SETTING--13 centres in UK, Belgium and Germany. SUBJECTS--127 immunocompetent patients with frequently recurring genital herpes. MAIN OUTCOME MEASURES--Proportions of patients reporting recurrences, recurrence frequency, and mean duration of lesions during breakthrough recurrences in each treatment group during a 6 month treatment period; time to first recurrence during treatment and follow-up after treatment cessation. RESULTS--During treatment, acyclovir recipients showed significant differences (p < 0.05) when compared with isoprinosine recipients in terms of a lower proportion reporting recurrences (31% vs 96%), a reduced mean number of reported recurrences per patient (0.6 vs 3.6), a shorter mean duration of breakthrough lesions (6.4 days vs 8.2 days), and a longer mean time (standard error) to first recurrence (143.7 (9.1) days vs 40.5 (5.4) days. The mean time to first recurrence after treatment cessation did not differ between the two groups. As compared with placebo recipients, isoprinosine treated patients had an increased recurrence frequency (3.6 vs 2.5) during treatment, and a shorter time to first recurrence after treatment cessation. All treatments were well tolerated without serious adverse events or toxicity. CONCLUSIONS--Acyclovir is very effective in suppressing recurrent genital herpes and is clearly superior to isoprinosine which is not clinically useful in the dosage studied.     

Recombinant interferon alfa-2b in plaque-phase mycosis fungoides. Intralesional and low-dose intramuscular therapy

A two-part clinical trial was conducted to determine the therapeutic efficacy of recombinant interferon alfa-2b in plaque-phase mycosis fungoides. In an initial randomized double-blind study, each of six patients had two representative plaques injected intralesionally with 1 X 10(6) U of recombinant interferon alfa-2b per site and two control plaques injected with placebo three times weekly for four consecutive weeks. Complete clinical regression of disease was observed at ten of 12 recombinant interferon alfa-2b sites compared with one of 12 placebo-treated sites four weeks after treatment with injections was stopped. Subsequently, in an open-labeled study, five of these patients were treated intramuscularly with 5 X 10(6) U of recombinant interferon alfa-2b three times weekly for four weeks and two patients were treated with a second, more extended course of therapy lasting 12 to 16 weeks. Three of the five patients treated systemically showed some improvement overall, but the responses were judged not to be clinically significant. The differential response observed from intralesional and intramuscular injections may be related to differences in concentration of recombinant interferon alfa-2b achieved in lesional skin by the two methods of administration.     

Valaciclovir for the suppression of recurrent genital HSV infection: a placebo controlled study of once daily therapy. International Valaciclovir HSV Study Group.

OBJECTIVE: To determine the efficacy and safety of once daily valaciclovir for the suppression of recurrent genital herpes simplex virus (HSV) infection in immunocompetent patients. METHODS: 382 otherwise healthy patients with a history of frequently recurring genital HSV infection (eight recurrences per year) were randomly allocated to receive either oral valaciclovir (500 mg once daily) or placebo (3:1 ratio) for 16 weeks or until the first genital HSV recurrence, whichever occurred first. Patients were clinically assessed at regular intervals and also if they experienced a recurrence. Safety was evaluated through adverse experience reporting and monitoring of haematology and biochemistry variables. On completion of the double blind phase, patients were eligible for follow up to a maximum of 48 weeks' treatment with open label valaciclovir (500 mg once daily) for further safety monitoring. The results from the double blind phase of the study are reported here. RESULTS: A significant difference was detected between valaciclovir and placebo in the time to first recurrence of genital HSV infection. The hazard ratio [95% confidence interval] for valaciclovir v placebo was 0.155 [0.112, 0.214], p < 0.0001. Valaciclovir prevented or delayed 85% of the recurrences that would have occurred with placebo. After 16 weeks (day 112) with treatment, 69% of patients receiving valaciclovir were recurrence free compared with only 9.5% of patients assigned to placebo. The safety profiles of valaciclovir and placebo were comparable, with adverse experiences being infrequent and generally mild. CONCLUSION: This study has demonstrated that once daily valaciclovir (500 mg), is highly effective and well tolerated for the suppression of recurrent genital HSV infection. Once daily dosing with valaciclovir provides a more convenient dosing regimen than the more frequent aciclovir regimens.     

Interferon alfa-2a in the treatment of Behçet disease: a randomized placebo-controlled and double-blind study

OBJECTIVE: To determine the therapeutic efficacy of interferon alfa-2a in the treatment of Beh?et disease. DESIGN: A randomized placebo-controlled and double-blind study. SETTING: University referral center. PATIENTS: Fifty patients with Beh?et disease were involved in the study. INTERVENTION: The patients were given interferon alfa-2a, 6 x 10(6) IU, subcutaneously 3 times per week or placebo for 3 months, and examined clinically at weekly intervals. MAIN OUTCOME MEASURES: For each mucocutaneous lesion and articular symptom, the mean frequency and duration were evaluated during the 3-month pretreatment, treatment, and follow-up periods. Pain for oral and genital ulcers was scored on a scale of 0 to 3. The ocular inflammatory score, the frequency of attacks, and changes in visual acuities for patients with ocular involvement were assessed before the study, at the end of treatment, and during the follow-up periods. In addition, overall responses at the end of the treatment period were graded as follows: complete remission, disappearance of all clinical signs and symptoms during treatment; partial remission, greater than a 50% decrease in the frequency, duration, and severity of pain for oral and genital ulcers and/or a decrease in the severity and frequency of ocular attacks; stable disease, less than a 50% change in the clinical signs and symptoms; and no effect or deterioration, ineffectiveness or worsening of clinical signs and symptoms. RESULTS: Twenty-three interferon alfa-2a- and 21 placebo-treated patients, ranging in age from 16 to 55 years (mean +/- SD age, 32.38 +/- 7.94 years), were evaluable for efficacy. Interferon alfa-2a treatment significantly decreased the duration (P=.02) and pain (P=.01) of oral ulcers and the frequency of genital ulcers (P=.03) and papulopustular lesions (P=.01). The mean frequency and duration of erythema nodosum-like lesions (P=.77 and.27, respectively), thrombophlebitis (P=.29 and.61, respectively), and articular symptoms (P=.92 and.74, respectively) also decreased. But there were no statistically significant differences. An improvement in the severity and the frequency of ocular attacks occurred in 5 of 6 patients in the interferon alfa-2a-treated group and in 1 of 3 patients in the placebo-treated group. Of the 23 patients in the interferon alfa-2a-treated group, 15 responded to treatment (2 complete and 13 partial responses); and of the 21 patients in the placebo group, 3 responded to treatment (3 partial responses) (P<.005). CONCLUSION: Interferon alfa-2a is an effective alternative treatment for Beh?et disease, particularly for the management of the mucocutaneous lesions of the disease.     

Cutaneous necrosis after injection of polyethylene glycol-modified interferon alfa

Pegylated interferon alfa-2b is a formulation of recombinant human interferon conjugated with polyethylene glycol. Compared with standard interferon alfa injections, this preparation has a longer half-life allowing for once-weekly injections and superior antiviral efficacy in the treatment of hepatitis C when used in combination with ribavirin. Cutaneous side effects caused by interferon are well known. Cutaneous necrosis as a result of interferon alfa is an infrequent complication with unknown pathogenesis, in which a cutaneous local immune-mediated inflammatory process might be involved. We report 5 patients (3 patients with chronic hepatitis C treated with pegylated interferon alfa-2b in association with oral ribavirin and two patients with chronic myelocytic leukemia) who developed local cutaneous reactions at sites of injection after the administration of weekly subcutaneous injections of pegylated interferon alfa-2b at different doses. The ulcers slowly healed with local therapy, but two patients required dose modification of the pegylated interferon alfa-2b and one patient required treatment withdrawal. We review the literature on previously reported cases of cutaneous necrosis after injection of standard interferon alfa or pegylated interferon alfa-2b and discuss the different pathophysiologic mechanisms that might be involved.     

Impact of suppressive antiviral therapy on the health related quality of life of patients with recurrent genital herpes infection

OBJECTIVE: To investigate whether suppressive antiviral therapy improves health related quality of life in patients with recurrent genital herpes. METHODS: Health related quality of life was measured using the disease specific recurrent genital herpes quality of life questionnaire (RGHQoL) as part of a randomized, double blind, 52 week, placebo controlled, dose ranging study of once and twice daily valaciclovir or aciclovir for the suppression of recurrent genital herpes in patients with six or more recurrences per year. RESULTS: Of 1479 participants, 1349 patients completed the baseline questionnaire. There were no significant baseline differences in RGHQoL score between any of the treatment groups. After 3 months there were significantly greater improvements in mean RGHQoL scores for all active treatment groups compared with placebo (p < 0.05). Mean RGHQoL score improvements from baseline remained significantly higher in the active treatment groups than in the placebo group after 6 and 12 months, indicating that the improved health related quality of life in patients receiving suppressive antiviral therapy was sustained over a prolonged period of time. CONCLUSION: Suppressive antiviral therapy is an effective strategy for improving the quality of life of patients with recurrent genital herpes. These improvements in quality of life are sustained over time, thus enhancing the clinical benefit in the long term management of this condition.     

Oral acyclovir suppression of recurrent genital herpes: a double-blind, placebo-controlled, crossover study

A randomised, double-blind, placebo-controlled, crossover study was conducted in 31 male patients with a history of frequently recurrent genital herpes who received consecutively 200 mg acyclovir and matching placebo by mouth four times a day for 12 weeks each. During acyclovir therapy recurrences were completely prevented in 24 (77%) and were reduced in both frequency and duration in the remainder compared with those occurring during treatment with placebo. The incidence and nature of adverse events reported during each treatment period was virtually identical. No long-term effects on recurrence rates were discernible but chronic suppressive therapy can be considered to offer the means of controlling the severe forms of disease experienced by some patients.     

Acyclovir prophylaxis of recurrent genital herpes: randomised placebo controlled crossover study.

Forty patients were entered into a randomised placebo controlled crossover study to assess the efficacy and safety of oral acyclovir 200 mg four times a day in the prophylaxis of recurrent genital herpes. Each treatment began during a recurrence and continued for a maximum of 84 days or until the onset of the next recurrence, when the alternate medication was started. Of 28 patients who completed both treatment courses, only three developed a recurrence while taking acyclovir compared with 26 while taking placebo. The mean time to first recurrence was more than 84 days in patients receiving acyclovir and 24 days in patients receiving placebo (p less than 0.001). The mean time to first recurrence after treatment with acyclovir ceased was 16 days. Adverse events, though thought unlikely to be related to treatment, necessitated the withdrawal from the study of two patients while taking acyclovir and one patient while taking placebo. No clinically important effects on haematological or biochemical variables occurred during the acyclovir treatment. All viral isolates tested after treatment remained sensitive to acyclovir. Acyclovir prophylaxis of recurrent genital herpes is effective and safe but does not appear to influence the natural history of the disease after cessation of 84 days' continuous treatment.     

泛昔洛韦联合转移因子治疗复发性生殖器疱疹疗效观察

目的:探讨泛昔洛韦联合转移因子治疗复发性生殖器疱疹的疗效。方法:治疗组32例,口服泛昔洛韦片,每次250mg,3次/d,连用10d后改为每次250mg,2次/d;同时口服转移因子胶囊,每次6mg,3次/d;两种药物联用2个月后停药。对照组28例,仅口服泛昔洛韦片,用法及疗程同治疗组。结果:治疗组的治愈率及总有效率均较对照组明显提高,复发率显著下降。结论:联合使用泛昔洛韦和转移因子是治疗复发性生殖器疱疹的一种有效的方法。     

A double-blind study of the efficacy and safety of the ICP10deltaPK vaccine against recurrent genital HSV-2 infections

A randomized double-blind trial to evaluate the safety of a novel recombinant virus, ICP10deltaPK, for reduction or prevention of recurrent herpes simplex virus type 2 (HSV-2) infection was carried out in public hospitals in Mexico City. Persons having a minimum of 5 documented herpetic recurrences in the previous year were randomized for vaccination. Patients were examined within 72 hours of lesion occurrence. If accepted into the study, the patient was inoculated subcutaneously in the upper deltoid muscle area at days 7, 17, and 28 after initiation of lesion occurrence. Recurrences were recorded by patient diary and physician examination. During the observation period (extending from 10 to 180 days after the last booster dose), recurrences in the vaccine (V) group were prevented completely in 37.5% of the patients, whereas in the placebo (P) group, 100% of the patients had at least one recurrence (P = .068). Vaccinated patients had fewer recurrences (V, 1.58; P, 3.13 [P = .028]). The mean number of illness days was 10 for the vaccine group and 18 for the placebo group (P = .028). Further studies to evaluate this vaccine and its dosimetry for the treatment of genital herpes infections appear warranted.     

Valaciclovir as a single dose during prodrome of herpes facialis: a pilot randomized double-blind clinical trial

BACKGROUND: Randomized clinical trials of valaciclovir in recurrent herpes labialis are lacking. OBJECTIVES: To determine whether a single course of valaciclovir, i.e. 500, 1000 or 2000 mg, administered during the prodrome of herpes facialis, could be beneficial. METHODS: Three hundred and forty-five out-patients with herpes labialis were screened and randomized for a multicentre, double-blind clinical trial. Ninety-six patients had no recurrence after 6 months of follow-up; 249 patients were finally included in the intent-to-treat (ITT) population. The main outcome measure was the rate of aborted episodes at day 3. The three treatment groups were similar at baseline. RESULTS: There was no statistically significant difference between the groups in rates of aborted lesions at day 3 in the ITT population, in particular between the 500 mg and 2000 mg treatment groups. CONCLUSIONS: Although a placebo group was not included in this pilot study, a single dose of valaciclovir was not considered beneficial in patients with recurrent herpes facialis.     

Recurrence of condylomata acuminata following cryotherapy is not prevented by systemically administered interferon.

OBJECTIVE--To determine whether interferon alpha-2a, when utilised as adjuvant chemotherapy following ablation of condylomata acuminata (genital warts) by cryotherapy, is effective in the prevention of recurrences. DESIGN--Randomised, placebo-controlled, double-blind study. Statistical analysis was by 2-tailed Fisher's Exact Test. PATIENTS--97 patients with recurrent condylomata acuminata. INTERVENTION--49 patients were treated with cryotherapy plus subcutaneously administered interferon alpha-2a, and 48 received cryotherapy plus placebo. Of these, 36 and 37 patients, respectively, completed the study and were evaluable. MAIN OUTCOME MEASURE--Clinical eradication of condylomata for six months following adjuvant chemotherapy. RESULTS--By completion of the adjuvant chemotherapy, 10 (28%) interferon recipients and 16 (43%) placebo recipients experienced recurrences. At six months follow-up, 25 (69%) interferon and 27 (73%) placebo recipients experienced recurrences. In the six months following interferon therapy, only 31% of interferon and 27% of placebo recipients remained free of recurrences (p = 0.99). CONCLUSIONS--Interferon alpha-2a administered subcutaneously offers no benefit as a chemotherapeutic adjuvant to cryotherapy when used alone in the therapy of genital warts in this population of patients with recurrent condylomata.     

Long-term oral acyclovir treatment prevents recurrent genital herpes

Thirty-three patients with frequently recurring genital herpes completed a randomized double-blind, crossover trial with oral acyclovir 200 mg 4 times a day and placebo for periods of 12 weeks. Five patients (15%) had full recurrence during acyclovir treatment and 31 (94%) while receiving placebo. The median time to first recurrence was 20 days for placebo and more than 84 days for acyclovir. It was concluded that acyclovir was well tolerated and an effective treatment to suppress the disease in selected cases of severe and frequently recurring genital herpes. However, the relapses seem to occur with the same rate as before, when the suppressive acyclovir treatment is stopped.     

万乃洛韦结合膦甲酸钠注射液治疗复发性生殖器疱疹的临床效果观察

目的：研究万乃洛韦结合膦甲酸钠注射液治疗复发性生殖器疱疹的临床效果。方法：本组抽取我院于2011年4月至2013年4月收治的复发性生殖器疱疹患者58例,将患者随机均分为两组,观察组患者采用万乃洛韦结合膦甲酸钠注射液治疗,对照组患者采用阿昔洛韦治疗,观察两组患者的临床疗效以及病情复发情况。结果：观察组患者的治疗有效率和1年内病情未复发率分别为100％、62．07％;对照组组患者的治疗有效率和1年内病情未复发率分别为79．31％、24．14％,差异具有统计学意义（P〈0．05）。结论：复发性生殖器疱疹患者入院后,取万乃洛韦结合膦甲酸钠注射液治疗,能够降低疾病的复发率,值得推广使用。     

An international, randomized, double-blind, placebo-controlled, study of valacyclovir for the suppression of herpes simplex virus type 2 genital herpes in newly diagnosed patients.

BACKGROUND: Antiviral suppressive therapy of genital herpes is often initiated based on the established pattern of recurrences in an individual. Because most persons with first episode herpes simplex virus type 2 (HSV-2) infection experience recurrences and because viral shedding occurs frequently in the first year after infection, we examined the strategy of initiating suppressive therapy shortly after diagnosis of genital HSV-2 infection. SUBJECTS AND METHODS: From June 16, 2004 to July 26, 2006, 384 subjects from 74 sites in the United States, Canada, Argentina, Brazil, and Chile who were newly diagnosed with a first recognized episode of genital herpes at the time of the screening visit or within 3 months before the screening visit were randomized (2:1) to receive valacyclovir 1 g once daily or placebo for 24 weeks. Subjects were instructed to return to clinic during suspected genital herpes outbreaks for clinician confirmation of recurrences. RESULTS: Valacyclovir significantly prolonged the time to first recurrence of HSV-2 genital herpes in newly diagnosed subjects compared with placebo, with approximately 43% of subjects on placebo and 71% of subjects on valacyclovir recurrence-free at 24 weeks (P <0.001). Valacyclovir significantly reduced the mean number of genital HSV-2 recurrences per month occurring during the 24-week study period (0.11 for valacyclovir, 0.48 for placebo, P <0.001). Adverse events were comparable in the valacyclovir and placebo arms. CONCLUSION: Valacyclovir 1 g once daily administered for 24 weeks was well-tolerated and effective in suppressing genital herpes recurrences in immunocompetent newly diagnosed persons without an established recurrence pattern.     

A randomised, double-blind, parallel group study to compare subcutaneous interferon alpha-2a plus podophyllin with placebo plus podophyllin in the treatment of primary condylomata acuminata.

OBJECTIVES--The primary objective was to determine if six weeks treatment with subcutaneous interferon alpha-2a (IFN) and podophyllin 25% W/V administered twice per week, preceded by IFN alpha-2a three times weekly for one week showed a greater complete response rate in patients with primary condylomata acuminata when assessed at week 10 than treatment with podophyllin and placebo injections in the same schedule. The secondary objective was to compare recurrence rates in complete responders at six months in the two treatment groups. DESIGN--Randomised, double-blind parallel group study. SETTING--Multicentre study in six genitourinary clinics within the U.K. PATIENTS--One hundred and twenty-four patients with primary anogenital warts. MAIN OUTCOME MEASURES--Complete response rate at week 10, and recurrence rate at week 26 in complete responders. RESULTS--At week 10 analysis of the efficacy population showed complete response in 36% (15/42 patients) of IFN-treated group and 26% (11/43 patients) in the placebo group (no significant difference). Analysis of the safety population at week 26 showed persistence of the complete response in 57% (8/14 patients) of the IFN-treated group and 80% (12/15 patients) of the placebo group (no significant difference). Adverse effects were more common in IFN-treated patients, involved particularly application site reaction and malaise but were generally mild. CONCLUSIONS--At the dose and with the regime described treatment with IFN alpha-2a in combination with podophyllin is no more effective in the treatment of primary anogenital warts than podophyllin alone and is associated with more adverse events.     

复发性生殖器疱疹患者血清IL-2及IL-10水平的检测

目的:探讨白介素-2(IL-2)和白介素-10(IL-10)在复发性生殖器疱疹发病机制中的作用.方法:采用酶联免疫吸附试验检测21例复发性生殖器疱疹患者血清IL-2及IL-10水平.结果:与正常人对照组相比,患者血清IL-2水平显著降低(P＜0.001),IL-10水平无明显改变(P＞0.05).结论:低水平IL-2使其诱生NK和LAK细胞活性降低而致溶解和破坏病毒感染的靶细胞能力低下,可能是生殖器疱疹复发的重要原因之一.     

阿昔洛韦联合阴道用乳杆菌胶囊治疗女性复发性生殖器疱疹的疗效分析

目的 探讨阿昔洛韦联合阴道用乳杆菌胶囊治疗单纯疱疹病毒(HSV)感染引起的女性复发性生殖器疱疹患者的疗效和安全性.方法 选取2016年10月至2018年10月四川省广安市人民医院诊治的220例复发性生殖器疱疹女性患者作为研究对象.按照随机数字表法分为观察组(n=110)和对照组(n=110).观察组口服阿昔洛韦片联合阴...