Genital Herpes Outbreaks Research Articles

Lifetime quality-adjusted life years lost due to genital herpes acquired in the United States in 2018: a mathematical modeling study

Genital herpes (GH), caused by herpes simplex virus type 1 and type 2 (HSV-1, HSV-2), is a common sexually transmitted disease associated with adverse health outcomes. Symptoms associated with GH outbreaks can be reduced by antiviral medications, but the infection is incurable and lifelong. In this study, we estimate the long-term health impacts of GH in the United States using quality-adjusted life years (QALYs) lost. We used probability trees to model the natural history of GH secondary to infection with HSV-1 and HSV-2 among people aged 18-49 years. We modelled the following outcomes to quantify the major causes of health losses following infection: symptomatic herpes outbreaks, psychosocial impacts associated with diagnosis and recurrences, urinary retention caused by sacral radiculitis, aseptic meningitis, Mollaret's meningitis, and neonatal herpes. The model was parameterized based on published literature on the natural history of GH. We summarized losses of health by computing the lifetime number of QALYs lost per genital HSV-1 and HSV-2 infection, and we combined this information with incidence estimates to compute the total lifetime number of QALYs lost due to infections acquired in 2018 in the United States. We estimated 0.05 (95% uncertainty interval (UI) 0.02-0.08) lifetime QALYs lost per incident GH infection acquired in 2018, equivalent to losing 0.05 years or about 18 days of life for one person with perfect health. The average number of QALYs lost per GH infection due to genital HSV-1 and HSV-2 was 0.01 (95% UI 0.01-0.02) and 0.05 (95% UI 0.02-0.09), respectively. The burden of genital HSV-1 is higher among women, while the burden of HSV-2 is higher among men. QALYs lost per neonatal herpes infection was estimated to be 7.93 (95% UI 6.63-9.19). At the population level, the total estimated lifetime QALYs lost as a result of GH infections acquired in 2018 was 33,100 (95% UI 12,600-67,900) due to GH in adults and 3,140 (95% UI 2,260-4,140) due to neonatal herpes. Results were most sensitive to assumptions on the magnitude of the disutility associated with post-diagnosis psychosocial distress and symptomatic recurrences. GH is associated with substantial health losses in the United States. Results from this study can be used to compare the burden of GH to other diseases, and it provides inputs that may be used in studies on the health impact and cost-effectiveness of interventions that aim to reduce the burden of GH. The Center for Disease Control and Prevention.

Quality of Life in women of reproductive age with recurrent genital herpes

Background: Current statistics show that the highest incidence of genital herpes is observed among women of reproductive age. Since these patients have an active lifestyle, frequent outbreaks of genital herpes can cause physical and psychological discomfort. Aim. To assess the quality of life of women of reproductive age with recurrent genital herpes. Methods: The quality of life in women suffering from recurrent genital herpes for more than 5 years (n=86) was evaluated. The control group included healthy women (n=91) according to the data of external genitalia examination and PCR diagnostics. The Health Status Survey (SF-36) in points was employed to measure the health status of women in both groups. Results: We established a significant difference between two groups of patients in terms of the influence of the following indicators on functional limitations: general health condition — 12.1±0.8 points; pain — 8.3±0.4 points; physical problems — 18,3±3,7; physical activity — 8.2±0.6 points (p<0.01). Conclusion: Symptoms of herpetic infection and longterm persistence have an impact on the performance of daily tasks and the quality of life of the patient.

Can oral antiviral drugs help prevent outbreaks of genital herpes?

Can oral antiviral drugs help prevent outbreaks of genital herpes?

Clinical Trial of Herbal Treatment Gene-Eden-VIR/Novirin in Oral Herpes.

Background.Our previous articles showed that suppressive or preventive treatment with the herbal Gene-Eden-VIR/Novirin reduced the number and duration of genital herpes outbreaks with no adverse effects. These studies also revealed that the herbal Gene-Eden-VIR/Novirin is mostly superior to acyclovir, valacyclovir, and famciclovir drugs in genital herpes. This study tested the effect of Gene-Eden-VIR/Novirin in oral herpes (also called cold sores and fever blisters).Methods.The framework of the study was a retrospective chart review. The study included 68 participants. The participants took 1 to 4 capsules per day over a period of 2 to 36 months. The study included 2 Food and Drug Administration–recommended controls: baseline and a no-treatment.Results.Gene-Eden-VIR/Novirin was effective in 89.3% of participants. The treatment reduced the mean number of outbreaks per year from 6.0 and 3.6 in the control groups to 2.0 in the treatment group (P < .0001 and P = .07, respectively). Gene-Eden-VIR/Novirin reduced the mean duration of outbreaks from 9.8 and 5.8 days in the control groups to 3.2 days in the treatment group (P < .0001 and P = .02, respectively). There were no reports of adverse experiences. Gene-Eden-VIR/Novirin was compared to acyclovir and valacyclovir in 6 tests. In all tests, Gene-Eden-VIR/Novirin showed higher efficacy. Gene-Eden-VIR/Novirin also showed superior safety.Conclusions.This clinical study showed that suppressive or preventive treatment with the herbal Gene-Eden-VIR/Novirin reduced the number and duration of outbreaks in oral herpes without any adverse effects. The study also showed that the herbal Gene-Eden-VIR/Novirin had better clinical effects than acyclovir and valacyclovir, the leading drugs in the category. Based on these results, we recommend using the herbal Gene-Eden-VIR/Novirin as preventive treatment for oral herpes and, specifically, as an alternative to the acyclovir and valacyclovir drugs.

Analysis of a Phase 2b Study of GEN-003, a Genital Herpes Immunotherapy, Showed Significant Reductions in Viral Shedding and Lesion Rate Vs Placebo

BackgroundGEN-003 is an investigational genital herpes immunotherapy comprising gD2ΔTMR, an HSV-2 antigen that induces neutralizing antibody and T cell responses, ICP4.2, an HSV-2 T cell antigen selected through human T cell screens, and Matrix-M2™, a saponin-based adjuvant. This Phase 2b study was designed to evaluate efficacy and safety of GEN-003 vs. placebo.MethodsHealthy persons, age 18–50 years, with 3–9 HSV-2 genital herpes outbreaks annually were randomized to 3 groups: placebo, or 60 µg of each antigen combined with 50 µg (60/50 group) or 75 µg (60/75 group) of adjuvant, administered 3 times 21 days apart. Study endpoints included safety, immunogenicity, HSV-2 shedding frequency, lesion rate and recurrence frequency. Viral shedding was measured from anogenital swabs by PCR. Swabs were collected for 28 days at baseline, and after the third dose, 6 months and 1 year. The presence of herpes lesions was recorded daily by electronic diary.ResultsOne hundred and thirty-one participants enrolled and >90% received all 3 doses. In the 28-day post-treatment period, viral shedding was reduced by 40% and 27% in the 60/50 and 60/75 groups, respectively, compared with a 5% increase in the placebo group. At 6 months post-treatment, median lesion rates were significantly lower in the 60/50 and 60/75 groups (2.7% and 1.9%, respectively) vs. the placebo group (5.6%, p < 0.05), resulting in median reductions of 52% and 66%. In participants not receiving suppressive antivirals, the median recurrence frequency was 1.0/6 months in the 60/50 group vs. 2.0 in the placebo group (p = 0.08). The median recurrence duration in the 60/50 group was lower than in the placebo group (2.8 vs. 4.2 days; p < 0.05). The most commonly reported adverse events (AEs) following GEN-003 vaccination were injection site pain/tenderness (97%), fatigue (82%), headache (82%) and myalgia (80%). No vaccine-related serious AEs, autoimmune events or other AEs of special interest were reported.ConclusionIn adults with recurrent genital herpes, GEN-003 reduced HSV-2 shedding frequency, genital herpes lesion rate, recurrence frequency and recurrence duration through 6 months after the last dose. Local and systemic symptoms were common in GEN-003 recipients, but treatment completion was high with few discontinuations due to AEs.Disclosures T. C. Heineman, GSK group of companies: Consultant and Shareholder, Consulting fee; D. Bernstein, Genocea Biosciences: Consultant and Investigator, Consulting fee and Research support; A. Wald, Genocea Biosciences: Investigator, Research grant and Support for travel to meetings for the study; N. Van Wagoner, Genocea Biosciences: Consultant, Research support and Travel support to present at scientific meetings; P. Leone, Genocea Biosciences: Grant Investigator and Scientific Advisor, Consulting fee, Research grant and Speaker honorarium; T. Oliphant, Genocea Biosciences: Consultant, Consulting fee; A. Natenshon, Genocea Biosciences: Employee, Salary; L. K. McNeil, Genocea Biosciences: Employee, Salary; J. B. Flechtner, Genocea Biosciences: Employee, Salary; S. Hetherington, Genocea Biosciences: Employee, Salary

Clinical study of Gene-Eden-VIR/Novirin in genital herpes: suppressive treatment safely decreases the duration of outbreaks in both severe and mild cases.

BackgroundWe conducted a clinical study that tested the effect of suppressive treatment with the botanical product Gene-Eden-VIR/Novirin on genital herpes. Our previous paper showed that the treatment decreased the number of genital herpes outbreaks without any side effects. It also showed that the clinical effects of Gene-Eden-VIR/Novirin are mostly better than those reported in the studies that tested acyclovir, valacyclovir, and famciclovir. The current paper reports the effect of suppressive treatment with Gene-Eden-VIR/Novirin on the duration of outbreaks, in severe and mild genital herpes cases.MethodsThe framework was a retrospective chart review. The population included 137 participants. The treatment was 1–4 capsules per day. The duration of treatment was 2–48 months. The study included three controls: baseline, no-treatment, and dose–response.ResultsThe treatment decreased the duration of outbreaks in 87 % of participants and decreased the mean duration of outbreaks from 8.77 days and 6.7 days in the control groups to 2.87 days in the treatment group (P < 0.001, both groups). All participants reported no adverse experiences.ConclusionsThis paper shows that suppressive treatment with Gene-Eden-VIR/Novirin decreased the duration of genital herpes outbreaks, in both severe and mild cases, without any side effects. Based on the results reported in this and our previous paper, we recommend suppressive treatment with Gene-Eden-VIR/Novirin as a natural alternative to both suppressive and episodic treatments with current drugs, in both severe and mild genital herpes cases. Trial registration ClinicalTrials.gov NCT02715752 Registered 17 March 2016 Retrospectively Registered

Clinical study in genital herpes: natural Gene-Eden-VIR/Novirin versus acyclovir, valacyclovir, and famciclovir.

BackgroundThis paper reports the results of a clinical study that tested the effect of suppressive treatment with the botanical product Gene-Eden-VIR/Novirin on the number of genital herpes outbreaks. The results in this study were compared to those published in clinical studies of acyclovir, valacyclovir, and famciclovir.MethodsThe framework was a retrospective chart review. The population included 139 participants. The treatment was one to four capsules of Gene-Eden-VIR/Novirin per day. The duration of treatment was 2–48 months. The study included three controls recommended by the US Food and Drug Administration (FDA): baseline, no treatment, and dose response.ResultsThe treatment decreased the number of outbreaks per year in 90.8% of the participants. The treatment also decreased the mean number of outbreaks per year from 7.27 and 5.5 in the control groups to 2.39 (P<0.0001 and P<0.001, respectively). The treated participants reported no adverse experiences. Out of the 15 tests that compared Gene-Eden-VIR/Novirin to the three drugs, Gene-Eden-VIR/Novirin had superior efficacy in eight tests, inferior efficacy in three tests, and comparable efficacy in four tests. Gene-Eden-VIR/Novirin also had superior safety.ConclusionThe clinical study showed that the natural Gene-Eden-VIR/Novirin decreases the number of genital herpes outbreaks without any side effects. The study also showed that the clinical effects reported in this study are mostly better than those reported in the reviewed studies of acyclovir, valacyclovir, and famciclovir.

A 51-Year-Old Man With Seizures and Progressive Behavioral Changes

A 51-year-old man was admitted for evaluation of new-onset generalized seizures in the context of progressive and significant behavioral change. His medical history was only notable for previous outbreaks of genital herpes. He took no medications. He had occasional social alcohol use and no illicit drug use but was a 35-pack-year current smoker. The patient had no relevant occupational exposure history but had recently traveled to Panama. Initially, the patient's significant other noticed a progressive flattening of his affect. The patient then started to experience episodes of "passing out" that led to injuries prompting ED visits. He was prescribed antiseizure medications and scheduled for an outpatient workup. However, with progressive gait instability, lethargy, and an increase in frequency of generalized seizures, the patient was admitted for treatment of suspected viral encephalitis. Despite initiation of antimicrobial and antiviral therapy, the patient's level of alertness continued to decline, ultimately leading to intubation for airway protection.

ACP Journal Club: review: oral antiviral drugs reduce clinical recurrence in recurrent genital herpes.

Source Citation Le Cleach L, Trinquart L, Do G, et al. Oral antiviral therapy for prevention of genital herpes outbreaks in immunocompetent and nonpregnant patients. Cochrane Database Syst Rev. 2014;8:CD009036. 25086573

Oral antiviral therapy for prevention of genital herpes outbreaks in immunocompetent and nonpregnant patients.

Genital herpes is caused by herpes simplex virus 1 (HSV-1) or 2 (HSV-2). Some infected people experience outbreaks of genital herpes, typically, characterized by vesicular and erosive localized painful genital lesions. To compare the effectiveness and safety of three oral antiviral drugs (acyclovir, famciclovir and valacyclovir) prescribed to suppress genital herpes outbreaks in non-pregnant patients. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, the search portal of the World Health Organization International Clinical Trials Registry Platform and pharmaceutical company databases up to February 2014. We also searched US Food and Drug Administration databases and proceedings of seven congresses to a maximum of 10 years. We contacted trial authors and pharmaceutical companies. We selected parallel-group and cross-over randomized controlled trials including patients with recurrent genital herpes caused by HSV, whatever the type (HSV-1, HSV-2, or undetermined), with at least four recurrences per year (trials concerning human immunodeficiency virus (HIV)-positive patients or pregnant women were not eligible) and comparing suppressive oral antiviral treatment with oral acyclovir, famciclovir, and valacyclovir versus placebo or another suppressive oral antiviral treatment. Two review authors independently selected eligible trials and extracted data. The Risk of bias tool was used to assess risk of bias. Treatment effect was measured by the risk ratio (RR) of having at least one genital herpes recurrence. Pooled RRs were derived by conventional pairwise meta-analyses. A network meta-analysis allowed for estimation of all possible two-by-two comparisons between antiviral drugs. A total of 26 trials (among which six had a cross-over design) were included. Among the 6950 randomly assigned participants, 54% (range 0 to 100%) were female, mean age was 35 years (range 26 to 45.1), and the mean number of recurrences per year was 11 (range 6.3 to 17.8). Duration of treatment was two to 12 months. Risk of bias was considered high for half of the studies and unclear for the other half. A total of 14 trials compared acyclovir versus placebo, four trials compared valacyclovir versus placebo and 2 trials compared valacyclovir versus no treatment. Three trials compared famciclovir versus placebo. Two trials compared valacyclovir versus famciclovir and one trial compared acyclovir versus valacyclovir versus placebo.We analyzed data from 22 trials for the outcome: risk of having at least one clinical recurrence. We could not obtain the outcome data for four trials. In placebo-controlled trials, there was a low quality evidence that the risk of having at least one clinical recurrence was reduced with acyclovir (nine parallel-group trials, n = 2049; pooled RR 0.48, 95% confidence interval (CI) 0.39 to 0.58), valacyclovir (four trials, n = 1788; pooled RR 0.41, 95% CI 0.24 to 0.69), or famciclovir (two trials, n = 732; pooled RR 0.57, 95% CI 0.50 to 0.64). The six cross-over trials showed larger treatment effects on average than the parallel-group trials. We found evidence of a small-study effect for acyclovir placebo-controlled trials (adjusted pooled RR 0.61, 95% CI 0.49 to 0.75). In analyzing parallel-group trials by daily dose, no clear evidence was found of a dose-response relationship for any drug. In head-to-head trials, the risk of having at least one recurrence was increased with valacyclovir rather than acyclovir (one trial, n = 1345; RR 1.16, 95% CI 1.01 to 1.34) and was not significantly different from that seen with famciclovir as compared with valacyclovir (one trial, n = 320; RR 1.18, 95% CI 0.86 to 1.63).We included 16 parallel-arm trials in a network meta-analysis and we were unable to determine which of the drugs was most effective in reducing the risk of at least one clinical recurrence (after adjustment for small-study effects, pooled RR 0.83, 95% CI 0.61 to 1.11 for valacyclovir vs acyclovir; pooled RR 1.04, 95% CI, 0.71 to 1.49 for famciclovir vs acyclovir; and pooled RR 1.26, 95% CI 0.89 to 1.75 for famciclovir vs valacyclovir). Safety data were sought but were reported as total numbers of adverse events. Owing to risk of bias and inconsistency, there is low quality evidence that suppressive antiviral therapy with acyclovir, valacyclovir or famciclovir in pacients experiencing at least four recurrences of genital herpes per year decreases the number of pacients with at least one recurrence as compared with placebo. Network meta-analysis of the few direct comparisons and the indirect comparisons did not show superiority of one drug over another.

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.

Changes in the Soluble Mucosal Immune Environment During Genital Herpes Outbreaks

Genital tract secretions provide variable inhibitory activity against herpes simplex virus (HSV) ex vivo. We hypothesize that the anti-HSV activity may prevent the spread of virus from the more commonly affected sites, such as the external genitalia, to the upper genital tract. The antimicrobial activity of cervicovaginal lavage (CVL) and concentrations of mucosal immune mediators were measured in 10 HIV-seronegative women with an active external herpetic lesion and compared with 10 HIV-seronegative women who were HSV-1 and HSV-2 seronegative. Samples were obtained at the time of a symptomatic external lesion (day 0), after 1 week of oral acyclovir (day 7), and 1 week after completing treatment (day 14). Controls were evaluated at parallel intervals. The anti-HSV activity was higher in CVL obtained from cases compared to controls at presentation (day 0) (54.3% vs. 28%), fell to similar levels on day 7, and then rebounded on day 14 (69% vs. 25%). The anti-HSV activity correlated positively and significantly with the concentrations of several inflammatory proteins; the concentrations of these proteins tended to be higher in cases compared with controls and followed a similar temporal pattern. Increases in inflammatory immune mediators and anti-HSV activity were detected in CVL at the time of clinical outbreaks and after completion of a short course of acyclovir. These mucosal responses may protect against HSV spread but could facilitate HIV infection and contribute to the clinical observation that, independent of clinical lesions, HSV-2 is a risk factor for HIV acquisition.

Immunity to Ocular and Genital Herpes Simplex Viruses Infections

Hindawi Publishing Corporation Clinical and Developmental Immunology Volume 2012, Article ID 732546, 2 pages doi:10.1155/2012/732546 Editorial Immunity to Ocular and Genital Herpes Simplex Viruses Infections Aziz Alami Chentoufi, 1 Lbachir BenMohamed, 2 Philippe Van De Perre, 3 and Ali A. Ashkar 4 1 Pathology and Clinical Laboratory Medicine, Department of Immunology, King Fahad Medical City, Riyadh 11525, Saudi Arabia of Cellular and Molecular Immunology, Gavin Herbert Eye Institute, College of Medicine, University of California, Irvine, CA 92697-4375, USA 3 INSERM U 1058, Universit´ e Montpellier 1, 34090 Montpellier, France 4 Department of Pathology and Molecular Medicine, McMaster Immunology Research Centre, McMaster University, Room MDCL4015, 1280 Main Street West, Hamilton, ON, Canada L8S 4K1 2 Laboratory Correspondence should be addressed to Aziz Alami Chentoufi, aachentoufi@kfmc.med.sa Received 20 November 2012; Accepted 20 November 2012 Copyright © 2012 Aziz Alami Chentoufi et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Herpes simplex virus type 1 and type 2 are amongst the most common human viral infection. Despite decades of research, currently, there is no vaccine or sterilizing therapy against human herpes. Both innate and adaptive immunities are required for protection against herpes infec- tions. However, the immunity and immunopathology of herpes infections are not yet fully characterized. To better understand the immunopathology of herpes infections and ultimately design an efficient prophylactic or therapeutic herpes vaccine or treatment, it is fundamental to define the cellular and molecular immune mechanisms and the immune correlates required for an efficient control of these ubiquitous pathogens. Over 400,000 Americans suffer from ocular herpes caused by HSV-1. Each year, nearly 50,000 new and recurring ocular herpes cases are diagnosed in the United States, with the more serious stromal keratitis accounting for about 25 percent. About 1 billion people— one-sixth of the world’s population—are infected with HSV- 2, the most common cause of genital herpes. In the United States, an estimated 50 million people carry the virus, and up to 3 million of those people suffer recurrent outbreaks of painful genital herpes. While the majority of HSV-1 and HSV-2 seropositive individuals is asymptomatic, a nonneg- ligible number of symptomatic individuals have as often as four recurrent herpes per year and required treatments. In addition, genital herpes has played an important role in driving the prevalence of other sexually transmitted infection such as HIV. Current drug therapies, often used to suppress genital herpes, can also treat ocular herpes but do not prevent future outbreaks. There is currently no prophylactic or therapeutic vaccine against herpes in the market. The impairment of T-cell function in acute and latent infection has been reported at many levels including abnormal antigen presentation in the periphery and in the sensory ganglia (trigeminal and lumbosacral ganglia), latently infected neuronal cells resistance to apoptosis by CD8+ T-cells, unbalanced immunoregulatory T-cell func- tion, and deregulation of Th1/Th2/Th17 axes. Despite the identification of many HSV-1 and HSV-2-antigens and their derived CD4+ and CD8+ T-cell epitopes, numerous antigen- specific therapies have failed when evaluated for their utility in the prevention and treatment of HSV infection. In this special issue, we invited authors to submit original research and review articles highlighting the recent advances that have broadened our understanding of immunity and immunopathology of herpes infection and HSV vaccine strategies. Also, we welcomed papers that seek to define immunoregulatory and effector properties of T-cells and dendritic cells to provide new insights as to their potential for clinical use. We were interested in articles that explore salient aspects of protective immunity throughout HSV latency, reactivation, ocular and genital herpetic disease, negative immunosynergy between HSV and HIV or other sexually transmitted diseases, and immunotherapeutical approaches. In a paper of this special issue, P. Stuart and T. Keadle documented the numerous recurrent models of herpetic stromal keratitis (HSK) that have been developed and how data generated from these models differs in some important

The Psychological Impact of Genital Herpes Stigma

This article reviews the psychological consequences of genital herpes infection through the lens of a recently proposed framework for conceptualizing concealable stigmas. We incorporate research on identity, stigma, and the connection between psychological and physical health to outline how negative stigma-related psychological consequences perpetuate distress associated with genital herpes. Our review of the research suggests a model linking negative affect and poor coping to frequent recurrences of genital herpes outbreaks. Frequent outbreaks, in turn, increase the salience of the stigma, reinforcing a stigmatized self-schema, thereby creating negative psychological consequences, continuing the cycle. We conclude by discussing the implications of this model for future research and mental health treatment.

Further Validation and Responsiveness Assessment of the Herpes Outbreak Impact Questionnaire and Herpes Symptom Checklist

Objective The Herpes Outbreak Impact Questionnaire (HOIQ) and Herpes Symptom Checklist (HSC) are patient-completed questionnaires for assessing genital herpes outbreaks. This report describes the validation of paper-and-pencil versions of the scales and responsiveness assessments in an Australian clinical trial. Methods Acceptability of the language of the original UK versions was tested with Australians. The HOIQ and HSC were then field-tested with patients. The new versions were validated using patients' daily responses to the questionnaires in a famciclovir study. Results The HOIQ and HSC were readily adapted into Australian English and were acceptable to patients. Psychometric sample: N = 151; 81 (54%) male; mean age 39.9 ± 11.6 years; mean outbreaks 5.1 ± 3.0 per year. Internal consistency was good (alphas at outbreak 1 ranged 0.84–0.90 HOIQ and 0.73–0.87 HSC). Rasch analysis showed item stability over time. Correlations between HOIQ and HSC ranged from 0.46 to 0.60. Both scales distinguished outbreak healing presence or absence at day 6 ( P = 0.001), and the HOIQ scale distinguished between symptom severity groups ( P < 0.001). Scale scores declined significantly over study duration, exhibiting large effect sizes. Conclusions The paper-and-pencil HOIQ and HSC were reliable, valid, and responsive in a clinical trial setting. These instruments are recommended for use in clinical studies.

The Development of the Herpes Symptom Checklist and the Herpes Outbreak Impact Questionnaire

Objective To develop measures of the day-to-day symptomatic and functional impact of recurrent genital herpes (RGH) outbreaks. The Herpes Outbreak Impact Questionnaire (HOIQ) and the Herpes Symptom Checklist (HSC) were designed to be acceptable to clinical professionals and to reflect patients' experience. Methods Scale content was derived via literature review and interviews with RGH patients and physicians. Questionnaires were assessed for face/content validity in the UK and the language checked for acceptability in the United States. The US measures were assessed for face/content validity with patients. Scaling/psychometric properties were determined via web survey. Participants completed the questionnaires twice during an outbreak, with 24 to 72 hours between administrations. Results Respondents found the questionnaires relevant and easy to understand and complete. Application of Rasch analysis resulted in the removal of two HOIQ items. Both scales were found to be unidimensional. Item stability testing for the HOIQ indicated that the measure is reproducible. Internal consistency was good (alpha: time 1 = 0.87, time 2 = 0.91). Discriminative validity was demonstrated by the measure's ability to distinguish between individuals who differed by self-reported severity of outbreak. The HOIQ and HSC were both responsive to change over time. Conclusions The HSC and the HOIQ can determine the impact of a herpes outbreak effectively. They are designed to be used daily during such outbreaks and to determine the effectiveness of RGH treatment.

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.

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

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. 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. 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. 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 meta-analysis to assess the efficacy of oral antiviral treatment to prevent genital herpes outbreaks

Efficacy of oral antiviral therapies, ie, acyclovir, valacyclovir (VACV), and famciclovir, for suppression of recurrent genital herpes was studied at different doses and regimens. We sought to compare the clinical efficacies of the different oral antiviral drugs prescribed prophylactically to suppress recurrent genital herpes. MEDLINE and EMBASE databases were searched for articles on genital herpes and selected antiviral drugs. The selected trials were: parallel randomized clinical trials testing prophylactic oral antiviral treatment of genital herpes versus placebo in immunocompetent and nonpregnant patients. Fourteen randomized clinical trials were selected, including a total of 6158 patients. The global relative risk of developing at least one recurrence during the study was reduced by 47% (95% confidence interval 45%-49%) in antiviral drug groups compared with the placebo. The best evaluated regimens, with comparable efficacies, were given twice daily, ie, acyclovir (400 mg twice daily), VACV (250 mg twice daily), and famciclovir (250 mg twice daily), or once daily (VACV 500 mg). The only end point available for all the studies was the number of patients presenting at least one recurrence of genital herpes during the observation period. The results of this first meta-analysis confirmed the high clinical efficacy of oral acyclovir, VACV, or famciclovir for prophylaxis against recurrent genital herpes.

Towards an effective genital herpes vaccine: past lessons and future prospects.

In 2007, the most effective means to acquire life-long immunity to genital herpes is to engage in romantic activity with a partner who is infected with herpes simplex virus 2 (HSV-2). Three out of four people who acquire HSV-2 in this manner are blissfully unaware of the molecular hitchhikers that they will carry for life, hidden away in neurons of their peripheral nervous system. Such persons derive a huge benefit from these molecular hitchhikers: life-long immunity from the disease of genital herpes. The natural approach to acquiring HSV-2 has a serious downside: 2 to 5% of HSV-2 infected people endure considerable pain and distress, as they may experience recurrent outbreaks of genital herpes every three to twelve months for the rest of their lives. About 1.5 billion people worldwide are infected with HSV-2, and ~50 million suffer from recurrent outbreaks of genital herpes. It is absurd to suggest that unprotected sex is the best means to vaccinate against HSV-2 and genital herpes. Yet, the sad reality in 2007 is that the medical community has about as much power to prevent genital herpes as doctors did who practiced in ancient Rome. The development of acyclovir in the late 1970s was a major breakthrough. It has provided a tool by which doctors and patients can restrict the severity and frequency of genital herpes outbreaks. However, a preventative vaccine that confers life-long protection against genital herpes continues to elude us. Tens of thousands of studies have been published on herpes simplex virus 1 (HSV-1) and HSV-2 in the past fifty years. These studies provide a wealth of information about the epidemiology, clinical presentation, immunology, molecular biology, and animal biology of HSV-1. Given that HSV-1 and HSV-2 share a nearly identical set of 75 genes, we possess an amazingly detailed knowledge about the biology of the infectious agents that cause recurrent herpes. So, how is it possible that progress in treating genital herpes has remained at a standstill for 30 years? I have grappled with this question for the past decade, and summarize my conclusions herein. My personal view is that a dichotomy in logic exists between 1. the approaches being most seriously considered to prevent genital herpes, and 2. the biology of herpes simplex virus infections. As the most thoroughly studied herpes vaccine candidate, the glycoprotein D subunit vaccine merits specific attention. However, I believe that the larger questions are: Why has an effective herpes vaccine eluded us for so long? What approaches are most likely to lead to an effective herpes vaccine? HSV-2 subunit vaccines: what have we learned? If one thinks of vaccine development in purely molecular terms, then an ideal HSV-2 vaccine would be a protein subunit of the virus that “jump starts” the adaptive immune response to HSV-2. Thus, HSV-2 vaccine development has focused on how to deliver immunodominant epitopes of HSV-2 to the immune system (1, 6, 25, 32, 38). Glycoprotein D is an immunodominant protein of HSV-1 and HSV-2. Clinical trials have been performed to determine if HSV-2 glycoprotein D can be used to protect people from HSV-2 infection and genital herpes. On both counts, the glycoprotein D subunit vaccine is marginally effective (29–31). Likewise, glycoprotein 120 subunit vaccines fail to protect people against human immunodeficiency virus infection and AIDS (5, 33, 39). Other attempts to produce HSV-2 vaccines have included killed, inactivated HSV-2 vaccines (27, 28), and replication-defective viral vectors (3, 7, 9, 20). In each case, I have reservations about the likelihood of success of the approach. Before proceeding, I wish to make clear my respect for the scientists who performed the studies on the HSV-2 glycoprotein D subunit vaccine. These individuals blazed a trail that simply did not exist ten years earlier. The glycoprotein D subunit may not be critical to the final formulation of a genital herpes vaccine, but what we have learned is invaluable. These studies have lifted a veil from the eyes of the scientific community, and have served as a catalyst that has scientists today asking the question, “What is necessary to attain an effective genital herpes vaccine?” There is no bigger success in science than to change (for the better) how your peers look at the natural world.