Treatment Of Recurrent Genital Herpes Research Articles

Additive manufacturing of TPU devices for genital herpes treatment with sustained acyclovir release

The treatment of recurrent genital herpes typically involves daily doses of acyclovir for extended periods. Additive manufacturing is an intriguing technique for creating personalised drug delivery systems, which can enhance the effectiveness of treatments for various diseases. The vaginal route offers a viable alternative for the systemic administration of drugs with low oral bioavailability. In this study, we produced different grades of thermoplastic polyurethane (TPU) filaments through hot-melt extrusion, with acyclovir concentrations of 0%, 10%, and 20% by weight. We used fused filament fabrication to manufacture matrix-based devices, including intrauterine devices and intravaginal rings. Our results, obtained through SEM, FTIR, and DSC analyses, confirm the successful incorporation of acyclovir into the matrix. Thermal analysis reveals that the manufacturing process alters the organization of the TPU chains, resulting in a slight reduction in crystallinity. In our in-vitro tests, we observed an initial burst release on the first day, followed by sustained release at reduced rates for up to 145 days, demonstrating their potential for long-term applications. Additionally, cytotoxicity analysis suggests the excellent biocompatibility of the printed devices, and biological assays show a remarkable 99% reduction in HSV-1 replication. In summary, TPU printed devices offer a promising alternative for long-term genital herpes treatment, with the results obtained potentially contributing to the advancement of pharmaceutical manufacturing.

Effects of Melatonin Alone or Associated with Acyclovir on the Suppressive Treatment of Recurrent Genital Herpes: A Prospective, Randomized, and Double-Blind Study

To evaluate the action of melatonin, acyclovir, or the association of melatonin with acyclovir as a suppressive treatment in women with recurrent genital herpes. The study was prospective, double-blind, and randomized, including 56 patients as follows: (a) The melatonin group received 180 placebo capsules in the 'day' container and 180 melatonin 3 mg capsules in the 'night' container (n = 19); (b) The acyclovir group received 360 capsules of 400 mg acyclovir twice a day (one capsule during the day and another during the night) (n = 15); (c) the melatonin group received 180 placebo capsules in the 'day' container and 180 melatonin 3 mg capsules in the 'night' container (n = 22). The length of treatment was six months. The follow-up after treatment was six months. Patients were evaluated before, during, and after treatment through clinical visits, laboratory tests, and the application of four questionnaires (QSF-36, Beck, Epworth, VAS, and LANNS). No statistically significant difference was observed for the depression and sleepiness questionnaires. However, in the Lanns scale for pain, all groups decreased the mean and median values in time (p = 0.001), without differentiation among the groups (p = 0.188). The recurrence rates of genital herpes within 60 days after treatment were 15.8%, 33.3%, and 36.4% in the melatonin, acyclovir, and association of melatonin with acyclovir groups, respectively. Our data suggest that melatonin may be an option for the suppressive treatment of recurrent genital herpes.

Integrative pharmacokinetic–pharmacodynamic modeling and simulation of amenamevir (ASP2151) for treatment of recurrent genital herpes

Amenamevir is a novel drug that targets the viral helicase–primase complex. While dose-dependent efficacy had been observed in non-clinical studies, no clear dose dependence has been observed in humans. We therefore developed a pharmacokinetic/pharmacodynamic (PK/PD) model to explain this inconsistency between species and to clarify the immune-related healing of amenamevir in humans. The model consisted of a non-linear kinetic model for a virtual number of virus plaques as a built-in biomarker. Lesion score was defined as an endpoint of antiviral efficacy, and logit model analysis was applied to the ordered-categorical lesion score. The modeling results suggested the time course profiles of lesion score could be explained with the efficacy terms in the logit model, using change in number of virus plaques as an indicator of the effects of amenamevir and time elapsed as an indicator of the healing of the immune response. In humans, the PD effect was almost dose-independent, and immune-related healing may have been the driving force behind the reduction in lesion scores. Drug efficacy is occasionally masked in diseases healed by the immune response, such as genital herpes. The PK/PD model proposed in the present study must be useful for explanation the PK/PD relationship of such drugs.

P10.18 Acyclovir 1 gm twice a day for 3 days for the treatment of recurrent genital herpes

Background Recurrent genital herpes is conventionally treated with acyclovir 200 mg 5 times a day orally which is inconvenient to take. We studied the effectiveness and safety of acyclovir 1 gm twice daily orally for 3 days in treatment of genital herpes. Methods Patients presenting with recurrent genital herpes were included in the study. After a complete clinical and laboratory evaluation, the patients were treated with acyclovir 1 gm twice daily orally for 3 days and followed up on days 3, 5 and 7 to determine the response to treatment and adverse effects. Results There were 23 patients (21 males and 2 females, between 18–55 years of age), of which 22 complete the study. Nine (41%) of them had complete healing of the ulcer on day 3, whereas 17 (77%) and 20 (91%) had it by day 5 and 7 respectively. Mean percentage healing of ulcer was 77.95 ± 26.03, 90.00 ± 16.20 and 95 ± 7.07 on day 3, 5, and 7 respectively. Visual analogue score (VAS) showed complete improvement in VAS in 9 (41%) patients on day 3, 21 (95.5%) on day 5 and 22 (100%) on day 7. The mean time of complete improvement in VAS was 4.27 ± 1.16 days. Mean of percentage improvement in VAS was 80.45 ± 25.30 on day 3 and 100 ± 0.00 on day 7. Mean healing time of the lesions was 4.67 ± 1.87 days (range 3–10 days). There were no significant adverse effects of the therapy. Conclusions The study demonstrated that oral acyclovir 1 gm twice daily is effective and safe for the treatment of recurrent genital herpes. There was rapid healing of lesions, which reduces morbidity, psychological distress and risk of transmission of infections to sexual partner. Further studies are however needed to confirm our results.

Противовирусная терапия при рецидивирующем генитальном герпесе

Herpes infection is one of the most common viral infections in man and presents a serious medical and social problem. In the Russian Federation, the incidence of genital herpes in 2012 amounted to 16.8 per 100 thousand population. The article deals with questions of clinic, diagnostics and applications of antiviral drug with immunomodulatory effects in the treatment of recurrent genital herpes.

Single-day therapy: an expert opinion on a recent development for the episodic treatment of recurrent genital herpes

One common method for treating recurrent genital herpes outbreaks is 3-5 day episodic therapy with nucleoside analogues. However, since maximum viral replication occurs within 24 h after the onset of symptoms, short-term patient-initiated episodic therapy started at prodromal onset or at the first appearance of lesions in patients without a prodrome may represent an important option. In a recent randomized trial, single-day Famciclovir treatment decreased lesion healing time and the duration of pain and other symptoms by approximately 2 days compared to placebo, and prevented progression to a full outbreak in almost one in four patients.

Resiquimod, a topical drug for viral skin lesions and skin cancer

Introduction: Resiquimod is an immune response modifier which stimulates cells through a toll-like receptors (TLR) 7 and 8 dependent pathway resulting in activation of immune responses that are effective against viral and tumor lesions.Areas covered: Studies on genital herpes, hepatitis C and actinic keratosis (AK) as well as papers of molecular activities of resiquimod were identified by a PubMed search. Although effective against genital HSV-2 in animal models, development of topical resiquimod for the treatment of recurrent genital herpes in humans was stopped due to inconsistent results in clinical trials. Reduction of HCV viral load was achieved by oral application but was associated with unacceptable side effects. Topical treatment of AK was well tolerated and effective with clearance rates higher compared to imiquimod. The molecular mode of action underlying the clinical efficacy primarily depends on cytokine induction in TLR7/8 expressing dendritic cells in the skin.Expert opinion: Topical resiquimod was shown to be a safe and effective treatment option for AK and appears to have potential as a treatment modality for patients with extended skin areas affected with AK (field cancerization). Resiquimod may also have potential for the therapy or prevention of epithelial viral infections.

One-day famciclovir vs. placebo in patient-initiated episodic treatment of recurrent genital herpes in immunocompetent Black patients

Background:There are no known racial differences in genital herpes disease pathogenesis or response to therapy. Despite high herpes simplex virus (HSV) seroprevalence in Black persons, clinical trials investigating the treatment of recurrent genital herpes (RGH) have typically enrolled a small proportion of Black patients.Methods:This multicenter, double-blind, placebo-controlled study evaluated the efficacy and safety of patient-initiated, 1-day famciclovir 1000 mg twice-daily in immunocompetent Black adults (USA and South Africa) with RGH. Eligible patients were randomized (2:1) to famciclovir or placebo. The primary endpoint was time to healing of non-aborted genital herpes lesions (i.e., lesions that progressed beyond papule stage). Secondary endpoints included proportion of patients with aborted genital herpes lesions, time to resolution of associated symptoms, and safety.Clinical trial registration:Trial registration: ClinicalTrials.gov identifier: NCT00477334.Results:A total of 299 patients with RGH (66% female, median age = 37 years) received either 1-day famciclovir 1000 mg twice-daily (n = 201) or placebo (n = 98). In the modified intent-to-treat population, the estimated median time to healing of non-aborted genital herpes lesions was 5.38 days for famciclovir and 4.79 days for placebo (median of treatment differences = 0.26 days; 95% CI [−0.40, 0.98]; p = 0.416). Consistent findings were reported in the completer and per-protocol populations. No significant differences were reported for all secondary analyses. Adverse events (AEs) were consistent with the established safety profile of famciclovir: 18 (6%) patients had drug-related AEs (16 [8%] famciclovir; 2 [2%] placebo), none of which were serious or led to discontinuation or dose adjustment/interruption. There are some limitations of this research: many study sites either lacked prior experience in conducting clinical studies in patients with HSV infection or enrolled small numbers of patients, which may have compromised efficacy outcomes. Also, HIV antibody testing was not mandated at enrollment.Conclusion:This study showed similar efficacy and tolerability of 1-day treatment with famciclovir 1000 mg twice-daily compared to placebo in immunocompetent Black adults with RGH. Famciclovir has proven efficacy and safety in the overall RGH population. Further understanding of the efficacy of antiherpes therapy in Black patients with recurrent genital herpes may be warranted.

Famciclovir treatment options for patients with frequent outbreaks of recurrent genital herpes: The RELIEF trial

Background Recurrent genital HSV outbreaks are common among those suffering from the disease. Antiviral medications taken as suppressive therapy can reduce the frequency of these recurrences and reduce viral shedding occurring in between recurrences. Objectives To investigate the efficacy and safety of oral famciclovir as episodic (125 mg twice daily for 5 days) and suppressive (250 mg twice daily) treatment of recurrent genital herpes (RGH). Study design This was a randomized, multicenter, 6-month, open-label study. Efficacy variables were time to first recurrence of RGH symptoms, and change in total score of the Recurrent Genital Herpes Quality of Life (RGHQoL) questionnaire. Subject satisfaction questions were summarized. Results 384 subjects were randomized. There was a highly statistically significant difference between treatments in time to first recurrence of symptoms in favor of suppressive treatment ( p < 0.0001). There was no significant difference between treatments in total score of the RGHQoL or in subject satisfaction with treatment. Conclusions This study demonstrated that, compared to episodic treatment, suppressive treatment with oral famciclovir may extend the time to symptomatic outbreaks in patients with frequent recurrences of genital herpes.

Has episodic treatment of recurrent genital herpes come of age?

Genitourinary medicine physicians have two main treatment options for the management of recurrent genital herpes: patient-initiated episodic or continuous suppressive therapy. As well as effective disease control, important factors in selecting a regimen include patient acceptability and potential improvements in quality of life. Traditionally suppressive therapy has been favoured by many genitourinary physicians who have often been sceptical of the benefits of episodic therapy. This view has been challenged by several recent studies demonstrating the efficacy and the comparable psychological benefits of very short patient-initiated episodic therapy compared with suppressive therapy. In this article, we review the theory and development of episodic therapy, and discuss the recent evidence that suggests the benefits of ultra short episodic therapies for recurrent genital herpes may be much greater than previously demonstrated.

A Comparison of One Year of Episodic or Suppressive Treatment of Recurrent Genital Herpes With Valacyclovir

We conducted this study to compare episodic and suppressive therapy for genital herpes about disease characteristics, disease burden, and psychologic impact. The authors conducted a randomized, open-label, 1-year treatment trial. Forty subjects were randomized to episodic therapy with valacyclovir (500 mg twice daily for 5 days) and 40 to suppressive therapy (500 mg daily). Subjects in the episodic arm experienced more outbreaks (7.87 +/- 4.65) than those in the suppressive arm (1.59 +/- 1.93) (P <0.001). Subjects in the episodic arm also had significantly more days with pain and lesions (6.5 +/- 7.3) than those in the suppressive arm (1.1 +/- 3.3) (P < 0.001), and other quantitative measures of disease burden also favored the suppressive arm. Both treatment groups had significant improvements in their recurrent genital herpes quality-of-life scores from baseline that persisted throughout the study; however, there was no significant difference between the treatment arms in these scores. Suppressive therapy of recurrent genital herpes with valacyclovir has a greater impact on measures of disease frequency and burden than episodic therapy. However, both treatment strategies lead to significant improvements in recurrent genital herpes quality-of-life scores. Both treatment strategies benefit patients with recurrent genital herpes.

Herpes simplex and varicella-zoster virus infections during pregnancy: current concepts of prevention, diagnosis and therapy. Part 1: Herpes simplex virus infections

Primary herpes simplex virus (HSV) infection may lead to severe illness in pregnancy and may be associated with transplacental virus transmission and fetal infection. The consequences may be abortion, stillbirth and congenital malformations. In neonates, the clinical findings after intrauterine HSV infection are characterized by skin lesions, diseases of the eye and neurologic damage. Herpes genitalis of pregnant women at the time of labor may result in life-threatening neonatal herpes. Currently, neither active nor passive immunization is available to prevent HSV infections during pregnancy and in the newborn infant. Therefore, antiviral treatment using aciclovir and/or valaciclovir must be considered in all primary episodes of genital herpes as well as in neonates who show signs of either infection. Clinical herpes lesions of the genitalia and/or positive test for virus detection at the time of delivery are an indication for cesarean section. However, this surgical intervention may be reduced by suppressive treatment of recurrent genital herpes with aciclovir or valaciclovir.

Famciclovir for the treatment of recurrent genital herpes: a clinical and pharmacological perspective

Herpes simplex virus is one of the most common causes of genital ulcer disease worldwide. Herpes simplex virus-2 is the more common cause of genital herpes, a chronic infection that is characterised by periodic reactivation, with the capacity to produce recurrent symptomatic disease in the host (e.g., vesicular eruption), as well as intermittent asymptomatic shedding. Relapsing episodes may be physically and psychologically distressing. Shedding accounts for the majority of cases of transmission of genital herpes to sexual partners. Pregnant women who are shedding may transmit the virus at the time of delivery, with severe and potentially fatal consequences to the baby. Famciclovir, a synthetic acyclic guanine derivative, is the prodrug of penciclovir, which demonstrates in vitro antiviral activity against various types of herpes virus, including herpes simplex virus-2. Its pharmacokinetics allow for administration in a convenient dosing regimen compared with acyclovir, which may improve compliance. Clinical studies have demonstrated its efficacy in the episodic treatment of relapses, with the most recent report demonstrating its efficacy and tolerance as a single-day treatment. It is also efficacious and well tolerated for the suppression of frequently recurring episodes. These results have been demonstrated in various patient populations, including immunocompetent patients and those infected with HIV. Famciclovir is well tolerated, with an adverse events profile similar to placebo.

Single-day therapy: an expert opinion on a recent development for the episodic treatment of recurrent genital herpes.

One common method for treating recurrent genital herpes outbreaks is 3–5 day episodic therapy with nucleoside analogues. However, since maximum viral replication occurs within 24 h after the onset of symptoms, short-term patient-initiated episodic therapy started at prodromal onset or at the first appearance of lesions in patients without a prodrome may represent an important option. In a recent randomized trial, single-day famciclovir treatment decreased lesion healing time and the duration of pain and other symptoms by approximately 2 days compared to placebo, and prevented progression to a full outbreak in almost one in four patients. Because single-day treatment is more convenient than traditional therapies, it may lead to improved patient compliance and better overall management of recurrent genital herpes outbreaks.

Valacyclovir for the treatment of genital herpes

Genital herpes is the most prevalent sexually transmitted infection in the USA. While sometimes mild in severity, it can be a distressing and painful chronic condition. Likewise, herpes labialis and herpes zoster can be both physically and psychologically painful. While there is no cure for these conditions, treatment to alleviate symptoms, suppress recurrences and reduce transmission has been drastically improved over the past 20 years with the use of guanine nucleoside antivirals, such as valacyclovir hydrochloride (Valtrex®, GlaxoSmithKline) the highly bioavailable prodrug of acyclovir (Zovirax®, GlaxoSmithKline), and famciclovir (Famvir®, Novartis), a highly bioavailable prodrug of penciclovir (Denavir®, Novartis). Clinical trials involving approximately 10,000 patients (including patients from nongenital herpes studies, such as herpes zoster) have assessed the safety and efficacy of valacyclovir in the treatment of initial genital herpes outbreaks, episodic treatment of recurrent episodes and daily suppressive therapy. It was shown that valacyclovir has similar efficacy to acyclovir in the episodic and suppressive treatment of genital herpes. Valacyclovir is the only antiviral drug approved for a once-daily dose of suppressive therapy for genital herpes, as well as the only antiviral drug US FDA approved for a 3-day regimen of episodic treatment of recurrent genital herpes. In addition, valacyclovir is also indicated in the reduction of the sexual transmission of herpes simplex virus infection and for the treatment of herpes labialis. In herpes zoster, valacyclovir is more effective than acyclovir or placebo (and as equally effective as famciclovir) in shortening the length and severity of herpes zoster-associated pain and postherpetic neuralgia. Valacyclovir has an acceptable safety profile in patients with herpes simplex and herpes zoster. The less frequent dosing regimen makes it an attractive option in the treatment of genital herpes and other viral infections, and may contribute to increased patient adherence to therapy.

Clinic-Initiated, Twice-Daily Oral Famciclovir for Treatment of Recurrent Genital Herpes: A Randomized, Double-blind, Controlled Trial

Clinic-Initiated, Twice-Daily Oral Famciclovir for Treatment of Recurrent Genital Herpes: A Randomized, Double-blind, Controlled Trial

Single-Day, Patient-Initiated Famciclovir Therapy for Recurrent Genital Herpes: A Randomized, Double-Blind, Placebo-Controlled Trial

Orally administered antiviral therapy for genital herpes improves the time to lesion healing and resolves symptoms during an outbreak. Although traditional therapy for a recurrent episode for healthy adults has consisted of twice-daily dosing for 5 days, recent studies have indicated that shorter courses of antiviral therapy are effective. This study was conducted to assess the efficacy and safety of a patient-initiated, single-day regimen of famciclovir therapy, compared with placebo, in immunocompetent adult patients with recurrent genital herpes. This multicenter, multinational, randomized, double-blind, parallel-group, placebo-controlled study compared single-day, patient-initiated oral famciclovir (1000 mg given twice daily) with placebo for the treatment of recurrent genital herpes. Patients were instructed to initiate therapy within 6 h after onset of prodromal symptoms or genital herpes lesions. Famciclovir reduced (P < .001) the time to healing of nonaborted lesions (i.e., those that progressed [corrected] beyond the papule stage) (median time, 4.3 vs. 6.1 days) and all nonaborted and aborted lesions (median time, 3.5 vs. 5.0 days), compared with placebo. The proportion of patients with aborted lesions was larger in the famciclovir group than in the placebo group (23.3% vs. 12.7%; P = .003). Adverse events in the famciclovir group were infrequent overall; most were of mild-to-moderate severity and were similar to adverse events in the placebo group. A single-day regimen of patient-initiated famciclovir treatment was well tolerated and safe, and the healing of recurrent genital herpes lesions occurred approximately 2 days faster than with placebo. Moreover, single-day famciclovir treatment stopped the development or progression of lesions beyond the papule stage. This convenient single-day regimen has the potential for improving patient compliance and satisfaction with therapy.

A randomized controlled trial of a replication defective (gH deletion) herpes simplex virus vaccine for the treatment of recurrent genital herpes among immunocompetent subjects

Background A replication incompetent herpes virus lacking the glycoprotein H gene has been developed as a potential therapeutic vaccine for genital herpes. Goal To determine vaccine efficacy on reducing HSV reactivation and clinical disease among immunocompetent persons with recurrent genital HSV-2 infection. Study design Randomized multicenter placebo-controlled trial. Healthy volunteers who had six or more recurrences of genital herpes per year were randomized to receive injections of vaccine at 0 and 8 or 0, 4, and 8 or 0, 2, 4, and 8 weeks or placebo and were followed for subsequent recurrences for 1 year. Results The median times to first recurrence of genital herpes (40 days versus 30 days versus 37 days versus 42 days, respectively), mean number of recurrences (3 versus 3 versus 2.4 versus 1.9, respectively), and time to lesion healing of the first recurrence (8 days versus 7.8 days versus 7.4 days versus 7.5 days, respectively), were similar for all treatment groups. Asymptomatic viral shedding was detected by PCR in 61/74 (82%) persons performing daily sample collection following completion of the vaccination series. No differences were noted in the proportion of days with shedding between treatment groups (11.9% versus 17.2% versus 13.1% versus 16.4%, respectively). Conclusion This replication incompetent HSV-2 vaccine lacking the glycoprotein H gene was safe but had no clinical or virologic benefit in the amelioration of genital HSV-2 disease among immunocompetent men and women.

Clinic-Initiated, Twice-Daily Oral Famciclovir for Treatment of Recurrent Genital Herpes: A Randomized, Double-Blind, Controlled Trial

Famciclovir, the oral prodrug of penciclovir, is effective for the treatment of recurrent genital herpes. This randomized, clinic-initiated, double-blind trial compared the therapeutic efficacy and safety of treatment with famciclovir at dosages of 125 mg, 250 mg, and 500 mg twice daily for 5 days with placebo in immunocompetent adults with a recurrent episode of genital herpes. Efficacy and tolerability were assessed in 308 patients with lesions present for no more than 6.5 h at the time of the first dose. Two assessments per day were performed to increase the precision of the determination of study end points. All doses of famciclovir were significantly more effective than placebo in reducing the time to cessation of viral shedding, complete lesion healing, and loss of all lesion-associated symptoms, particularly lesion tenderness, pain, and itching. Patients receiving treatment with famciclovir were significantly less likely to experience new lesions than were patients receiving placebo. All doses of famciclovir were tolerated as well as placebo was. There was no difference in efficacy or tolerability among the different doses of famciclovir; the lowest effective dose was 125 mg twice per day. In immunocompetent adults with recurrent genital herpes, a 5-day course of famciclovir at a dosage of 125 mg, 250 mg, or 500 mg twice per day was significantly more effective than was placebo in reducing the duration of viral shedding and symptoms and in accelerating lesion healing. These results support the use of treatment with famciclovir at a dosage of 125 mg for 5 days as an effective, well-tolerated treatment for episodes of recurrent genital herpes.

Valacyclovir in the treatment of herpes simplex, herpes zoster, and other viral infections.

Genital herpes and herpes labialis are prevalent, physically and psychologically painful, and often disabling. Herpes zoster is often very painful and may result in months or years of postherpetic neuralgia (PHN). Over the past two decades, the treatment of these conditions has been transformed by guanosine nucleoside antivirals such as valacyclovir (Valtrex, a highly bioavailable prodrug of acyclovir (Zovirax, and famciclovir (Famvir), a highly bioavailable prodrug of penciclovir (Denavir). We describe the pharmacology, pharmacokinetics, and clinical efficacy of valacyclovir for the treatment of herpes simplex, herpes zoster, and other viral infections. Valacyclovir is also compared with acyclovir and famciclovir. All published literature containing the word "valacyclovir" was reviewed and summarized. Valacyclovir is the only oral antiviral agent approved for therapy of herpes labialis, the only antiviral drug approved for a 3-day course in the episodic treatment of recurrent genital herpes, as well as the only antiviral drug approved for once daily dosing for suppressive therapy. In herpes zoster, valacyclovir is more effective than acyclovir and equally effective as famciclovir at hastening the healing of zoster-associated pain and PHN. Valacyclovir is safe and effective in the therapy of patients with herpes simplex and herpes zoster and may be useful in other viral infections.