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Disclaimer: CME certification for these activities has expired. All information is pertinent to the timeframe in which it was released.

Emerging Issues in the Management of Herpes Simplex Virus Infections

To provide primary care physicians, obstetricians/gynecologists, and dermatologists with up-to-date information on the treatment of patients with herpes virus.

This activity is designed for primary care physicians, obstetricians/gynecologists, and dermatologists active in the treatment of patients with herpes virus. No prerequisites required.

The Johns Hopkins University School of Medicine takes responsibility for the content, quality, and scientific integrity of this CME activity. At the conclusion of this activity, the participant should be able to:

  • Explain the common presentations of genital herpes (GH) infection, including classic, atypical or nonclassic, and asymptomatic.
  •  Analyze research on the role of pharmacologic agents in reducing the duration of GH lesions.
  • Describe management options for GH infection, including initial, episodic, and suppressive approaches to treatment.
  • Discuss approaches to overcoming patient and system barriers to successful management of GH infection.

The Johns Hopkins University School of Medicine is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.

The Johns Hopkins University School of Medicine designates this educational activity for a maximum of 2 AMA PRA Category 1 Credit(s)™. Physicians should only claim credit commensurate with the extent of their participation in the activity.

The estimated time to complete this educational activity: 2 hours.

Release date: December 15, 2006. Expiration date: December 15, 2008.

The opinions and recommendations expressed by faculty and other experts whose input is included in this program are their own. This enduring material is produced for educational purposes only. Use of The Johns Hopkins University School of Medicine name implies review of educational format, design, and approach. Please review the complete prescribing information of specific drugs or combinations of drugs, including indications, contraindications, warnings, and adverse effects, before administering pharmacologic therapy to patients.

This program is supported by an educational grant from Novartis Pharmaceuticals.

Full Disclosure Policy Affecting CME Activities:
As a provider accredited by the Accreditation Council for Continuing Medical Education (ACCME), it is the policy of the Johns Hopkins University School of Medicine to require the disclosure of the existence of any significant financial interest or any other relationship a faculty member or a sponsor has with the manufacturer(s) of any commercial product(s) discussed in an educational presentation. The Program Director and Participating Faculty reported the following:


Anne M. Rompalo, MD
Professor, Department of Medicine
Division of Infectious Disease
Johns Hopkins School of Medicine
Baltimore, Maryland
Dr Rompalo reports receiving honoraria from GlaxoSmithKline and Merck and Company.


Stephen A. Brunton, MD
Director of Faculty Development
Stamford Hospital
Columbia University
Charlotte, North Carolina
Cabarrus Family Medicine Residency Program
Concord, North Carolina
Dr Brunton reports serving as a consultant for Novartis Pharmaceuticals; and receiving other financial and material support from the American Herpes Foundation.

Lisa M. Hollier, MD, MPH
Associate Professor and Residency Program Director
Department of Obstetrics, Gynecology, and Reproductive Sciences
University of Texas Houston Medical School
Houston, Texas
Dr Hollier reports having no financial or advisory relationships with corporate organizations related to this activity.

Stephen K. Tyring, MD, PhD
Adjunct Professor
Departments of Microbiology & Immunology, Dermatology, and Internal Medicine
University of Texas Health Science Center
Houston, Texas
Dr Tyring reports receiving grants/research support from, serving as a consultant for, receiving honoraria from, and serving on the speakers' bureau for GlaxoSmithKline, Merck and Company, and Novartis Pharmaceuticals.

Richard J. Whitley, MD
Department of Pediatrics, Microbiology, Medicine, and Neurosurgery
University of Alabama at Birmingham
Birmingham, Alabama
Dr Whitley reports receiving grants/research support from National Institutes of Health; serving as a consultant for Achillion, Chimerix, and Gilead Sciences; receiving honoraria from four Grand Rounds at academic institutions; and serving on the speakers' bureau for GlaxoSmithKline and Novartis Pharmaceuticals.

Notice: The audience is advised that articles in this CME activity contain reference(s) to unlabeled or unapproved uses of drugs or devices.

Drs Brunton, Hollier, Tyring, and Whitley—suppression of herpes labialis with acyclovir, valacyclovir, and famciclovir.

All other faculty have indicated that they have not referenced unlabeled/unapproved uses of drugs or devices.

Johns Hopkins Advanced Studies in Medicine provides disclosure information from contributing authors, lead presenters, and participating faculty. Johns Hopkins Advanced Studies in Medicine does not provide disclosure information from authors of abstracts and poster presentations. The reader shall be advised that these contributors may or may not maintain financial relationships with pharmaceutical companies.

Emerging Issues in the Management of Herpes Simplex Virus Infections
Anne M. Rompalo, MD*

Genital herpes, caused by infection with herpes simplex virus type 1 (HSV-1) or type 2 (HSV-2), is one of the most common sexually transmitted diseases in the United States and impacts the lives of millions of infected individuals and their partners. Because genital herpes is an incurable, remitting-recurring disease, the focus of therapy is on symptom reduction, prevention of recurrences, and suppression of transmission. Many individuals with genital herpes suffer significant negative psychological and psychosocial effects in addition to the physical pain and other symptoms associated with active disease. In special populations, such as immunocompromised individuals, those patients coinfected with human immunodeficiency virus (HIV), or neonates who acquire HSV during pregnancy, HSV infection may be associated with serious morbidity or death.

The recurrent nature of genital herpes can be particularly troubling to patients, underscoring a sense of loss of control that often accompanies the disease. The nucleoside antivirals acyclovir, famciclovir, and valacyclovir have all demonstrated effectiveness as treatment for initial or recurrent episodes and as suppressive therapy, but many patients report being dissatisfied with management of their disease, particularly with respect to treatment of initial or recurrent episodes.

This issue of Johns Hopkins Advanced Studies in Medicine contains a review article prepared by 4 experts in herpes infection. It examines various aspects of genital herpes and its management, including a focus on patient-initiated therapy and the use of shorter or simplified treatment regimens as potential means to improve outcomes and reduce drug costs. The first section of the review article presents an updated overview of the epidemiology and medical costs associated with genital herpes. Although HSV-2 seroprevalence in the United States increased dramatically in the latter half of the 20th century, the most recent report from the National Health and Nutrition Examination Survey (NHANES IV) suggests the trajectory of increasing seroprevalence may have reversed in the beginning portion of the 21st century. That notwithstanding, it has been estimated that 60 million individuals in the United States may be infected with HSV-2 by the year 2025 and, although precise medical costs have been difficult to determine, total costs for incident HSV-2 infections have been estimated to be as high as $2.7 billion by 2025 in some mathematical models. More than 50% of estimated total direct costs are attributable to drug expenditures.

The second section of this article discusses clinical manifestations and diagnosis of genital herpes. In addition to physical signs and symptoms of genital herpes, psychological and psychosocial aspects of the disease are also examined. Notably, many patients do not experience classical signs of genital herpes, and both initial and recurrent episodes may be unrecognized or asymptomatic. Asymptomatic infection is associated with viral shedding and is a major source of transmission to uninfected partners. Also of note, lesion formation is often preceded by prodromal symptoms that can be used by patients to initiate treatment early in the course of recurrent episodes, with possible improved outcomes. Diagnostic tests for genital herpes include laboratory approaches for the detection of antigens or nucleic acids in lesions and type-specific serologic tests that have become increasingly important in the identification of patients with asymptomatic or unrecognized genital herpes.

Treatments and treatment goals are examined next. Acyclovir, famciclovir, and valacyclovir remain the standard of care and may be used as suppressive therapy or to treat initial or recurrent episodes of genital herpes. Each has been shown to decrease the severity and duration of symptoms, shorten the time of viral shedding, and reduce the frequency of recurrences. By decreasing viral shedding, antiviral therapy may reduce the risk of transmission. Despite these benefits, large numbers of patients remain dissatisfied with current care, particularly with respect to episodic treatment. The article discusses a recently approved 1-day regimen of famciclovir for patient-initiated treatment of recurrent genital herpes that is hoped will improve compliance and outcomes, in addition to possibly reducing total drug costs. Once-daily administration of valacyclovir as suppressive therapy may also improve compliance, outcomes, and patient satisfaction, compared to twice-daily suppressive regimens of valacyclovir or acyclovir.

The last section of the review article describes special issues in genital herpes management, namely, the issues of management of pregnant women with genital herpes and the interrelationships between HSV and HIV infection. Neonates of women with HSV may become infected during pregnancy or the birthing process, and the consequences can be devastating, including neurologic impairment or death. Because antiviral therapy is often insufficient, even when provided early after diagnosis, the focus of neonatal herpes is on prevention. Strategies for prevention are largely nonpharmacological, although the American College of Obstetrics and Gynecologists recommends giving antiviral therapy to women with primary HSV during pregnancy, and considering antiviral therapy for women at or beyond 36 weeks of gestation with a first episode of HSV occurring during pregnancy. The final and perhaps most troubling issue examined in this article is the association between HSV infection and HIV acquisition or progression. Antiviral HSV therapy is effective in controlling recurrence and shedding of HSV in HIV-infected individuals and, in the future, may be proven beneficial in decreasing HIV transmission or acquisition.

We hope the information provided in this monograph will help to improve the management of patients with genital herpes by expanding knowledge about the disease and its current treatment strategies and regimens.

*Professor, Department of Medicine, Division of Infectious Disease, Johns Hopkins School of Medicine, Baltimore, Maryland.
Address correspondence to: Anne M. Rompalo, MD, Professor, Department of Medicine, Division of Infectious Disease, Johns Hopkins Bayview Medical Center, Mason F. Lord Building, Center Tower, 5200 Eastern Avenue, Suite 4000, Room 427, Baltimore, MD 21224.

The content in this monograph was developed with the assistance of a staff medical writer. Each author had final approval of his/her article and all its contents.

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