Three phase III randomized controlled trials of topical resiquimod 0.01-percent gel to reduce anogenital herpes recurrences.

Resiquimod, a Toll-like receptor 7 and 8 agonist, stimulates production of cytokines that promote an antigen-specific T helper type 1 acquired immune response. Animal and phase II human trials showed posttreatment efficacy in reducing recurrent herpes lesion days and/or time to first recurrence. Three phase III randomized, double-blind, vehicle-controlled trials of topical resiquimod to reduce anogenital herpes recurrences were conducted in healthy adults with ≥4 recurrences within the prior year.

Novel composite efficacy measure to demonstrate the rationale and efficacy of combination antiviral-anti-inflammatory treatment for recurrent herpes simplex labialis.

Historically, the primary target for research and treatment of recurrent herpes simplex labialis (HSL) has been limited to inhibiting herpes simplex virus (HSV) replication. Antiviral monotherapy, however, has proven only marginally effective in curtailing the duration and severity of recurrent lesions. Recently, the role of inflammation in the progression and resolution of recurrences has been identified as an additional target.

Transcranial Doppler quantification of residual shunt after percutaneous patent foramen ovale closure: correlation of device efficacy with intracardiac anatomic measures.

Background: Percutaneous, mechanical closure of defects of the atrial septum fails to completely resolve shunting in up to 20% of cases. Little is known about the factors associated with device failure.

Methods: We measured the left atrial opening (X), right atrial opening (Z), tunnel length (Y), septum secundum, device-septum primum separation, and tunnel compressibility of the patent foramen ovale (PFO) in 301 patients with cryptogenic neurological events, PFO anatomy, and severe Valsalva shunting (Spencer Grade 5-5+).

Transcranial doppler quantification of residual shunt after percutaneous patent foramen ovale closure: efficacy of the GORE(®) HELEX septal occluder.

Background: Ideally, percutaneous, mechanical closure of defects of the atrial septum should completely resolve shunt. To achieve this goal, more information is needed about the factors associated with device failure.

Methods: Consecutive patients with cryptogenic neurological events who had severe baseline Valsalva shunt (Spencer Grade 5-5+) and intracardiac echocardiography (ICE) defined patent foramen ovale (PFO) who underwent percutaneous PFO closure with the GORE(®) HELEX Septal Occluder device were evaluated for residual 3-month shunt by transcranial Doppler (TCD).

Early treatment of cold sores with topical ME-609 decreases the frequency of ulcerative lesions: a randomized, double-blind, placebo-controlled, patient-initiated clinical trial.

Background: Prior pilot studies support the use of antiviral medications with topical corticosteroids for herpes simplex labialis (HSL). ME-609 (Xerese, Xerclear) is a combination of 5% acyclovir and 1% hydrocortisone developed for the topical treatment of HSL.

Objectives: The primary study end point was the prevention of ulcerative HSL lesions.

Prevention of ulcerative lesions by episodic treatment of recurrent herpes labialis: A literature review.

There are substantial difficulties involved in carrying out clinical studies of recurrent herpes labialis, since the disease has a rapid onset, short-lasting viral shedding period and is rapidly self-healing. The aim of this paper was to critically assess published reports of episodic treatment of herpes labialis and to review biological and methodological problems involved in such studies. Limited, but statistically significant, results have been shown with topical antivirals, such as acyclovir and penciclovir, improving healing times by approximately 10%.

Valacyclovir and topical clobetasol gel for the episodic treatment of herpes labialis: a patient-initiated, double-blind, placebo-controlled pilot trial.

Background: Treatment of herpes simplex labialis (HSL) has been associated with modest benefits. This difficulty results from the rapid resolution of the disease accomplished by the immune system, which narrows the window of therapeutic opportunity. The immune response is also responsible for important clinical manifestations, including oedema and pain.

Situational antiviral drug prophylaxis for HSV type 1 recurrences.

Recurrent herpes simplex virus type 1 infection is generally associated with mild morbidity. However, frequent recurrences may have a significant psychosocial impact, and reactivation in certain high-risk situations may cause considerable morbidity. Controlled trials demonstrate that antiviral drug prophylaxis can be efficacious in selected circumstances; even for other situations, clinical reports suggest that such antiviral drug prophylaxis remains effective.

An update on short-course intermittent and prevention therapies for herpes labialis.

Infection with herpes simplex virus (HSV) has increased in prevalence worldwide over the past two decades, making it a major public health concern. Approximately 90% of recurrent HSV type 1 (HSV-1) infections manifest as non-genital disease, primarily as orofacial lesions known as herpes labialis. Improvements in our understanding of the natural history of herpes labialis support the rationale for early treatment (during the prodrome or erythema stages) with high doses of antiviral agents in order to maximize drug benefit.

Single-dose famciclovir for the treatment of herpes labialis.

Background: Approximately 20% to 40% of the population experience recurrent herpes labialis caused by herpes simplex virus type 1 (HSV-1). Since there is no cure, patients typically use antiviral therapy to treat outbreaks as they occur. A large proportion of patients self-administer topical antiviral therapies at the onset of symptoms, but lack of efficacy, frequent dosing, and inconvenient long-term treatment regimens have made the use of oral antiviral therapies more common.

Topical iontophoretic administration of acyclovir for the episodic treatment of herpes labialis: a randomized, double-blind, placebo-controlled, clinic-initiated trial.

Background: Multiple studies of the use of acyclovir for the treatment of herpes labialis have suggested that the nominal efficacy of the topical formulation is the result of inadequate penetration of the drug into the target site of infection, the basal epidermis.

Methods: We developed a low-voltage, wireless, hand-held, computer-controlled, iontophoretic applicator to enhance the skin penetration of topical acyclovir in the treatment of herpes labialis. We performed a multicenter, placebo-controlled, clinic-initiated, pilot trial of a single, topical, iontophoretic application of 5% acyclovir cream for the episodic treatment of herpes labialis among 200 patients with an incipient cold sore outbreak at the erythema or papular/edema lesion stage.

Single-dose, patient-initiated famciclovir: a randomized, double-blind, placebo-controlled trial for episodic treatment of herpes labialis.

Background: The brief period of viral replication in recurrent herpes labialis lesions suggests shorter therapeutic regimens are a logical episodic treatment strategy.

Objective: We sought to assess the efficacy and safety of single-dose and single-day famciclovir treatments.

Methods: In all, 701 randomly assigned patients self-initiated therapy with famciclovir (1500 mg once [single dose] or 750 mg twice a day for 1 day [single day]) or placebo within 1 hour of onset of the prodromal symptoms of an episode of herpes labialis.

Evaluation of imiquimod 5% cream to modify the natural history of herpes labialis: a pilot study.

Background: Imiquimod is currently approved for the treatment of genital warts and has been shown to decrease recurrences of genital herpes in the guinea pig model of genital herpes. Therefore, we evaluated the safety and potential of topical imiquimod to decrease the rate of recurrence in humans with a history of recurrent herpes labialis.

Methods: Forty-seven subjects with recurrent herpes labialis applied imiquimod 5% (n=30) or vehicle cream (n=17) to recurrent lesion(s) on days 1, 3, and 5 of the study (day 1 of observation occurred within 48 h after recurrence of lesion).

Recurrent antiviral-resistant genital herpes in an immunocompetent patient.

Herpes simplex virus type 2 (HSV-2) resistance to antiviral drugs has been described primarily in immunocompromised patients. We report an apparently immunocompetent, human immunodeficiency virus-negative male patient who has experienced repeated HSV-2 genital outbreaks despite receiving antiviral prophylaxis with several different drugs. Several of the HSV-2 genital isolates from this patient have been confirmed as resistant to acyclovir and penciclovir.

HSV-2 transmission.

A number of important risk factors for the acquisition of HSV-2 have been established including female gender, black or Hispanic ethnic origin, HIV infection, age, and increased number of sexual partners. Transmission is influenced by a number of biological factors such as sexual behavior, use of condoms, duration of relationships, and knowledge of a partner's serologic status. Vertical transmission (transmission of HSV from mother to neonate) is potentially life-threatening; neonatal HSV infection is associated with significant morbidity and mortality.

HSV shedding.

Viral shedding of HSV occurs frequently in infected individuals. HSV is shed asymptomatically from multiple anatomical sites and shedding, like exposure, is a significant risk for transmission. However, the relationship between shedding frequency, viral titer and transmission is unknown.

Lessons from HIV and hepatitis viruses.

Surrogate markers are an important component in the process of investigating management and prevention strategies, and for increasing understanding of viral diseases. The importance of surrogate markers and applied statistical models is particularly true for HIV. For HIV infection, the development of such methods provides new approaches for evaluation of HIV therapies and vaccines, and for the study of HIV transmission and its pathogenesis.

Introduction: Is viral shedding a surrogate marker for transmission of genital herpes?

Genital herpes, caused by either herpes simplex virus type 1 or 2 (HSV-1 and HSV-2), is a significant public health problem worldwide. It increases the risk of infection with HIV, upregulates HIV after infection and can be associated with serious morbidity and mortality. It is now known that clinical and subclinical viral reactivation with resultant shedding from anogenital mucosa occurs frequently, resulting in transmission during sexual contact.

Multiple sclerosis attacks are associated with picornavirus infections.

Multiple sclerosis (MS) is a chronic demyelinating disease of the central nervous system, which often follows a relapsing-remitting (RR) course with discrete attacks. MS attacks have been associated with upper respiratory infections (URIs), but the specific viruses responsible have not been identified. We studied a cohort of 16 RRMS patients experiencing URI and followed them for clinically identifiable attacks.

Clinical significance of antiviral therapy for episodic treatment of herpes labialis: exploratory analyses of the combined data from two valaciclovir trials.

Valaciclovir (Valtrex) 2 g twice daily for 1 day was recently approved in the United States for treatment of cold sores. In order to apply more clinically relevant assumptions to the analysis, we examined the effect of different missing data and endpoint assumptions on apparent valaciclovir efficacy. Results of each analysis demonstrate statistically significant increases in the proportion of subjects whose cold sores were aborted with valaciclovir compared with placebo, and significant decreases in healing times for subjects with cold sore lesions who were treated with valaciclovir compared with placebo.

STAT1 binds to the herpes simplex virus type 1 latency-associated transcript promoter.

The authors hypothesized that environmental stimuli induce cytokines that act through an intracellular cascade, which includes signal transducers and activators of transcription (STATs), to change herpes simplex virus (HSV) gene expression, thereby inducing viral reactivation. The HSV type 1 (HSV-1) latency-associated transcript (LAT) gene regulates viral reactivation within neurons via an unknown mechanism. HSV-1 deletion mutants that are missing key portions of the LAT gene, particularly the 3' region of the LAT promoter, do not reactivate normally in vivo.

Susceptibility of herpes simplex virus isolates to nucleoside analogues and the proportion of nucleoside-resistant variants after repeated topical application of penciclovir to recurrent herpes labialis.

Subjects received topical penciclovir for 4 days during successive episodes of recurrent herpes labialis. Isolation of herpes simplex virus (HSV) was attempted from lesions obtained before initiation of treatment and on each day of therapy. Isolates remained sensitive to penciclovir when tested by a plaque reduction assay, and there was no significant change in sensitivity during any treatment course or between successive treatments.