Effects of Different Doses of GEN-003, a Therapeutic Vaccine for Genital Herpes Simplex Virus-2, on Viral Shedding and Lesions: Results of a Randomized Placebo-Controlled Trial.

Background: GEN-003 is a candidate therapeutic vaccine for genital herpes simplex virus type 2 (HSV-2). We compared virologic and clinical impact of varying GEN-003 doses.

Methods: Adults with symptomatic HSV-2 received placebo or GEN-003 (30 or 60 µg antigen with 25, 50, or 75 µg adjuvant).

Performance of Commercial Enzyme-Linked Immunoassays for Diagnosis of Herpes Simplex Virus-1 and Herpes Simplex Virus-2 Infection in a Clinical Setting.

Background: US Food and Drug Administration-approved enzyme-linked immunoassays (EIA) for determining type-specific herpes simplex virus (HSV) serostatus are widely used in clinical practice. We compared the performance of such assays with the University of Washington Western blot (UW WB) in patients who sought confirmation of their HSV serology result.

Methods: We reviewed charts of all persons evaluated at the Westover Heights Clinic in Portland, Oregon, from July 2010 through September 2015, who had a HSV EIA, followed by UW WB.

Therapeutic Vaccine for Genital Herpes Simplex Virus-2 Infection: Findings From a Randomized Trial.

Background: Genital herpes simplex virus type 2 (HSV-2) infection causes recurrent lesions and frequent viral shedding. GEN-003 is a candidate therapeutic vaccine containing HSV-2 gD2∆TMR and ICP4.2, and Matrix-M2 adjuvant.

Effect of Pritelivir Compared With Valacyclovir on Genital HSV-2 Shedding in Patients With Frequent Recurrences: A Randomized Clinical Trial.

Importance: Current therapy of herpes infections relies on nucleoside analogues. Pritelivir is a well-tolerated novel herpes simplex virus (HSV) helicase-primase inhibitor that reduced genital shedding and lesions.

Objective: To compare the efficacy of pritelivir with valacyclovir for suppression of genital HSV-2 infection.

HLA Class I and II alleles, heterozygosity and HLA-KIR interactions are associated with rates of genital HSV shedding and lesions.

Variation at HLA and KIR loci is associated with the severity of viral infections. To assess associations of genital HSV-2 infection with human HLA and KIR genetic loci, we measured the frequencies of genital herpes simplex virus (HSV) DNA detection and of genital lesions in HSV-2 seropositive persons. We followed 267 HSV-2 seropositive persons who collected daily genital swabs and recorded lesions for ⩾30 days.

No Evidence of Pritelivir Resistance Among Herpes Simplex Virus Type 2 Isolates After 4 Weeks of Daily Therapy.

Background: Pritelivir is a novel helicase-primase inhibitor in clinical development for treatment of herpes simplex virus type 2 (HSV-2) infections. In preclinical work, resistance-mediating mutations were identified in the HSV-2 genome at 3 loci in the UL5 gene and 1 locus in UL52.

Methods: To evaluate whether daily pritelivir treatment results in emergence of resistance-mediating mutations, we analyzed HSV-2 strains detected in genital swab specimens from trial participants who were randomly assigned to receive different dosages of pritelivir.

Type-specific identification of anogenital herpes simplex virus infections by use of a commercially available nucleic acid amplification test.

Herpes infections are among the most common sexually transmitted infections (STI), but diagnostic methods for genital herpes have not kept pace with the movement toward molecular testing. Here, we describe an FDA-approved molecular assay that identifies and types herpes simplex virus (HSV) infections for use in routine clinical settings. Paired samples from anogenital lesions were tested using the BD ProbeTec HSV Q(x) (HSVQ(x)) system, HSV culture and, a laboratory-developed PCR assay.

Safety and immunogenicity of long HSV-2 peptides complexed with rhHsc70 in HSV-2 seropositive persons.

HSV-2, the primary causative agent of genital herpes, establishes latency in sensory ganglia and reactivates causing recurrent lesions and viral shedding. Induction or expansion of CD4(+) and CD8(+) T cell responses are expected to be important for a successful therapeutic vaccine against HSV-2. A candidate vaccine consisting of 32 synthetic 35mer HSV-2 peptides non-covalently complexed with recombinant human Hsc70 protein (named HerpV, formerly AG-707) was tested for safety and immunogenicity in a Phase I study.

Genital shedding of herpes simplex virus among symptomatic and asymptomatic persons with HSV-2 infection.

Context: Since herpes simplex virus type 2 (HSV-2) antibody tests have become commercially available, an increasing number of persons have learned that they have genital herpes through serologic testing. The course of natural history of HSV-2 in asymptomatic, seropositive persons is uncertain.

Objective: To evaluate the virologic and clinical course of HSV genital shedding among individuals with symptomatic and asymptomatic HSV-2 infection.

Persistent genital herpes simplex virus-2 shedding years following the first clinical episode.

Background: Patients with newly acquired genital herpes simplex virus 2 (HSV-2) infection have virus frequently detected at the genital mucosa. Rates of genital shedding initially decrease over time after infection, but data on long-term viral shedding are lacking.

Methods: For this study, 377 healthy adults with history of symptomatic genital HSV-2 infection collected anogenital swabs for HSV-2 DNA polymerase chain reaction for at least 30 consecutive days.

Phase I clinical trial of MPC-6827 (Azixa), a microtubule destabilizing agent, in patients with advanced cancer.

MPC-6827 (Azixa) is a small-molecule microtubule-destabilizing agent that binds to the same (or nearby) sites on β-tubulin as colchicine. This phase I study was designed to determine the dose-limiting toxicities (DLT), maximum tolerated dose (MTD), and pharmacokinetics (PK) of MPC-6827 in patients with solid tumors. Patients with advanced/metastatic cancer were treated with once-weekly, 1- to 2-hour intravenous administration of MPC-6827 for 3 consecutive weeks every 28 days (1 cycle).

Availability of serologic and virologic testing for herpes simplex virus in the largest sexually transmitted disease clinics in the United States.

Background: The prevalence of herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) in the United States is estimated to be 57.7% for HSV 1 and 17.0% for HSV 2.

APOE genotype is associated with oral herpetic lesions but not genital or oral herpes simplex virus shedding.

Background: Apolipoprotein E is polymorphic in the human population. APOE4 has previously been reported to correlate with symptomatic oral and genital herpes disease.

Methods: APOE was genotyped in 182 subjects with herpes simplex virus (HSV) 2 and in 62 subjects with HSV-1, including 44 subjects with both viral types for a total of 200 adults.

A phase I study of weekly R1507, a human monoclonal antibody insulin-like growth factor-I receptor antagonist, in patients with advanced solid tumors.

Purpose: A phase I study was conducted to evaluate the pharmacokinetics, pharmacodynamics, safety, and tolerability of R1507-a fully human IgG1 type monoclonal antibody directed against the human insulin-like growth factor-I receptor.

Experimental Design: Patients with advanced solid tumors were assigned to receive i.v.

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.

One-day regimen of valacyclovir for treatment of recurrent genital herpes simplex virus 2 infection.

Objectives: To evaluate the efficacy of a 1-day course of valacyclovir in reducing the duration and severity of genital herpes recurrences and to measure the frequency of viral shedding episodes subsequent to antiviral therapy.

Study Design: In an open-label pilot study, patients with recurrent genital herpes simplex virus 2 (HSV-2) infection were given a 1-day course of valacyclovir (2000 mg given by mouth twice daily) to be taken at the first sign of recurrence or prodrome. Participants maintained diaries of signs and symptoms and collected genital swabs for viral culture while lesions persisted and HSV DNA PCR for 14 days after initiating treatment.

Phase I dose-escalation study of a monovalent heat shock protein 70-herpes simplex virus type 2 (HSV-2) peptide-based vaccine designed to prime or boost CD8 T-cell responses in HSV-naïve and HSV-2-infected subjects.

This was a phase I study to assess the safety, tolerability, and immunogenicity of escalating doses of AG-702, a noncovalent complex of an HLA A*0201-restricted epitope in the glycoprotein B protein of herpes simplex virus type 2 (gB2) and truncated human constitutive heat shock protein 70. Similar vaccines have been immunogenic in animals. Three injections of 10 to 250 mug were administered intradermally to HLA A*0201-bearing subjects who were either herpes simplex virus type 2 (HSV-2)-infected or HSV uninfected.

The effect of daily valacyclovir suppression on herpes simplex virus type 2 viral shedding in HSV-2 seropositive subjects without a history of genital herpes.

Background: A substantial number of HSV-2 seropositive individuals lack a history of clinically recognized genital herpes. These individuals can transmit disease during periods of asymptomatic viral shedding. The frequency of asymptomatic shedding and the efficacy of antiviral therapy in reducing shedding has not been assessed in this population.

From the NIH: proceedings of a workshop on the importance of self-obtained vaginal specimens for detection of sexually transmitted infections.

On June 27, 2006, the NIH conducted a workshop to review published data and current field practices supporting the use of self-obtained vaginal swabs (SOVs) as specimens for diagnosis of sexually transmitted infections (STIs). The workshop also explored the design of studies that could support FDA clearance of SOVs for STI testing, particularly for specimens collected in nonclinical settings including patients' homes. This report summarizes the workshop findings and recommendations.

Genital herpes.

Genital herpes is the main cause of genital ulcers worldwide; the prevalence of herpes simplex virus (HSV) type 2 infections in the general population ranges from 10% to 60%. Most genital herpes is caused by HSV-2, although HSV-1 accounts for about half of new cases in developed countries. The risk of HIV acquisition is three times higher in people with HSV-2.

Famciclovir reduces viral mucosal shedding in HSV-seropositive persons.

Objective: Many cases of herpes simplex virus (HSV) infection occur through asymptomatic shedding from persons without evidence of clinical disease. This study explores whether famciclovir reduces HSV shedding in HSV-2 seropositive persons with or without a history of symptomatic genital herpes.

Study Design: One hundred twenty-seven HSV-2 seropositive participants were randomly assigned to 42 days of famciclovir, followed by 14 days of washout and 42 days of placebo, or vice versa.

Topical resiquimod 0.01% gel decreases herpes simplex virus type 2 genital shedding: a randomized, controlled trial.

Background: Resiquimod, an investigational immune response modifier and Toll-like receptor (TLR) 7 and 8 agonist, stimulates production of cytokines that promote an antigen-specific T helper type 1 (Th1)--acquired immune response. In animal models, induction of Th1-specific responses modifies experimental herpes simplex virus (HSV) infection.

Methods: We conducted a randomized, double-blind, vehicle-controlled trial to assess the efficacy of resiquimod 0.

Suppressive therapy with valacyclovir in early genital herpes: a pilot study of clinical efficacy and herpes-related quality of life.

Background: Suppressive therapy has not been studied during the first year after acquisition of genital herpes, the time of maximum frequency of reactivation, potential for transmission, and impact on quality of life.

Objective: The objective of this study was to evaluate the effectiveness of suppressive therapy with valacyclovir initiated within 3 months of infection.

Study Design: The authors conducted a double-blind, randomized, controlled trial of 1.

Effect of valacyclovir on viral shedding in immunocompetent patients with recurrent herpes simplex virus 2 genital herpes: a US-based randomized, double-blind, placebo-controlled clinical trial.

Objective: To determine the efficacy of daily suppressive therapy with a 1-g dose of valacyclovir in reducing total (clinical and subclinical) herpes simplex virus 2 (HSV-2) shedding compared with placebo in Immunocompetent patients diagnosed as having recurrent HSV-2 genital herpes.

Patients And Methods: From June 18, 2004, to December 17, 2004, patients from 27 US sites with a history of 6 or more genital herpes recurrences per year were randomized in a 3:1 ratio to receive 1 g/d of valacyclovir or placebo. During the double-blind suppressive therapy, patients were provided with the study drug (500-mg valacyclovir caplets or matching placebo) and Instructed to take 2 caplets once daily without regard to meals for 60 days.