Recently the CDC updated its guidelines for treating sexually transmitted diseases (STDs).¹ In last month's issue (CONSULTANT, June 2002, page 849), the recommendations for managing sexually transmitted bacterial diseases were discussed. Here the focus is on genital herpes simplex virus (HSV) infection and human papillomavirus (HPV) infection. In a future issue, sexually transmitted fungal and protozoan infections, as well as pediculosis pubis and scabies, will be addressed.

Highlights of the new guidelines for treating viral STDs, which are provided below, include:

• Renewed emphasis on counseling for patients with genital herpes and those with HPV infection.
• Improved type-specific serologic tests for HSV.
• Updated dosing recommendations and alternative regimens.
• Tips for follow-up.

GENITAL HERPES

At least 50 million Americans have genital HSV infection. This recurrent, incurable disease remains undiagnosed in most infected persons; they often have mild or asymptomatic infections and shed virus intermittently in the genital tract. Although systemic antiviral drugs can partially control the signs and symptoms of herpes, they do not eradicate latent virus and have no effect on recurrence after therapy is discontinued.

Figure 1

Diagnosis. The clinical diagnosis of genital herpes is both insensitive and nonspecific. Many infected persons do not have the typical painful multiple vesicular or ulcerative lesions (Figure 1). Thus, laboratory testing is necessary to confirm the diagnosis and to determine the HSV serotype. Two HSV serotypes have been identified: HSV-1 and HSV-2. Although HSV-1 causes up to 30% of the first episodes of genital herpes, recurrences are much less common with HSV-1 infection than with HSV-2 infection.

Virologic tests. Isolation of HSV in cell culture is the preferred virologic test in patients who have genital ulcers or other mucocutaneous lesions. The sensitivity of culture declines rapidly as lesions begin to heal, usually within a few days of onset. Polymerase chain reaction assay for HSV DNA is the test of choice for detecting HSV in the spinal fluid of patients with suspected CNS involvement.

Type-specific serologic tests. Because false-negative HSV cultures are common, especially in patients with recurrent infection or healing lesions, these tests are useful in confirming a clinical diagnosis of genital herpes. They can also be used to diagnose asymptomatic infection and to test sex partners of infected patients. Routine screening for HSV infection in the general population, however, is not recommended.

Both type-specific and nonspecific antibodies to HSV develop during the first several weeks following infection and persist indefinitely. Accurate type-specific assays for HSV antibodies must be based on the HSV-specific glycoprotein G2 for the diagnosis of HSV-2 infection and glycoprotein G1 for HSV-1 infection. These assays became available in 1999; older assays do not accurately distinguish HSV-1 from HSV-2 antibody. Specifically request a type-specific gG-based assay when ordering serologic testing.

The sensitivities of these tests for detection of HSV-2 antibody vary from 80% to 98%, and false-negative results may occur, especially in the early stages of infection. The specificities of these assays are at least 96%. False-positives can occur, especially in patients with a low likelihood of HSV infection, and a second test may be required.

Primary infection. Management of the first clinical episode of genital herpes includes systemic antiviral medication (acyclovir, famciclovir, or valacyclovir) and counseling. Recommended regimens are listed in Table 1. Topical antiviral therapy, which provides only minimal benefit, is not recommended.

Counseling is an important aspect of management, not only at the initial visit but also at follow-up visits, after the acute illness subsides. When talking to patients about genital herpes, be sure to:

• Discuss the benefits of episodic and suppressive antiviral therapy with patients who are having a first episode of genital herpes.
• Emphasize the potential for recurrence, asymptomatic viral shedding, and sexual transmission when you describe the natural history of the disease.
• Advise patients to abstain from sexual activity when lesions or prodromal symptoms are present. Encourage them to tell their partners that they have genital herpes.
• Advocate the use of latex condoms during all sexual exposures with new or uninfected partners.
• Counsel patients that sexual transmission of HSV can occur during asymptomatic periods. Asymptomatic viral shedding occurs more frequently in patients who have HSV-2 infection and in those who have had genital herpes for less than 12 months.
• Explain the risk of neonatal transmission to all patients, including men. Tell women who are of childbearing age to inform all their health care providers of the HSV infection if they become pregnant.
• Advise the sex partners of patients with genital herpes that they might be infected even if they have no symptoms. Offer type-specific serologic testing to the partner.
• Provide the same counseling to patients with asymptomatic HSV-2 infection detected by serologic testing that those who have symptomatic infection receive. Antiviral therapy is not recommended for persons who have no clinical manifestations of infection.

Recurrent infection. Most patients who have a first episode of genital HSV-2 infection will have recurrences. Episodic antiviral therapy can ameliorate or shorten the duration of the lesions; suppressive therapy can reduce the frequency of recurrences.

Episodic therapy can benefit many patients who have recurrent disease when treatment is started during the prodrome or within 1 day after the onset of lesions. Provide the patient with antiviral therapy or a prescription for the medication so that treatment can be initiated during this window of opportunity.

Daily suppressive therapy reduces the frequency of recurrences by at least 70% among patients who have 6 or more recurrent episodes per year. Daily acyclovir therapy has been shown to be safe and effective for up to 6 years; daily therapy with valacyclovir or famciclovir, for 1 year.

After 1 year of continuous suppressive therapy, discuss terminating treatment with the patient. In many patients, the frequency of recurrences decreases over time.

Suppressive antiviral therapy reduces but does not eliminate asymptomatic viral shedding. Thus, the extent to which such therapy may prevent HSV transmission is unknown.

Both valacyclovir and famciclovir are comparable to acyclovir in terms of clinical outcome.^2-6 Valacyclovir, 500 mg/d, may be less effective than other valacyclovir or acyclovir regimens in patients with numerous recurrences (10 or more episodes per year). Consider cost and ease of administration when selecting an agent for long-term antiviral therapy.

Severe disease. Intravenous antiviral therapy is required for patients who have severe HSV infection or complications that mandate hospitalization, such as disseminated infection, pneumonitis, hepatitis, or CNS complications (eg, meningitis or encephalitis). The recommended regimen is IV acyclovir, 5 to 10 mg/kg q8h for 2 to 7 days or until symptoms are resolved. This is followed by oral antiviral therapy to complete a total of 10 days of treatment.