What are the management and treatment options for a patient with a reactive Roche (Electrochemiluminescence immunoassay) Elecsys (Electrochemiluminescence immunoassay system) Herpes Simplex Virus type 2 (HSV-2) Immunoglobulin G (IgG) assay result?

Management of Reactive Roche Elecsys HSV-2 IgG Assay

A reactive HSV-2 IgG result indicates past exposure and ongoing latent infection, but requires confirmation if the index value is <3.0 before proceeding with counseling and management decisions. 1, 2

First Critical Step: Confirm the Diagnosis

Before any clinical action, verify the index value of your Roche Elecsys result:

• If index value is 1.1-2.9: This has only 39.8% specificity, meaning more than half are false positives—confirmation with a second test using different glycoprotein G antigen (such as Biokit HSV-2 rapid assay or Western blot) is essential 1, 2
• If index value is ≥3.0: Specificity improves to 78.6%, but false positives still occur and confirmation may be warranted depending on clinical context 1
• Using Biokit HSV-2 rapid assay as confirmatory testing improves specificity from 93.2% to 98.7% compared to Western blot 1
• False positives are particularly common in individuals with HSV-1 infection, especially at low index values 1

Common pitfall: Proceeding with counseling and treatment decisions based on low-positive results without confirmation leads to unnecessary psychological distress and inappropriate management 2

Determine If Screening Was Appropriate

• The US Preventive Services Task Force recommends against routine serologic screening for HSV-2 in asymptomatic adults because harms outweigh benefits 2
• Appropriate screening scenarios include: persons with genital symptoms, persons told they have genital herpes without virologic confirmation, sexual partners of HSV-2-infected individuals, HIV-infected persons, and pregnant women at risk of acquiring HSV near delivery 2

Management Based on Clinical Presentation

For Asymptomatic Patients (Confirmed Positive)

Comprehensive counseling is the cornerstone of management:

• Explain that HSV-2 is a chronic, lifelong infection with antibodies persisting indefinitely 1
• Discuss natural history: recurrent genital herpes outbreaks occur 1-12 times per year, though many individuals remain asymptomatic 3
• Address asymptomatic viral shedding and sexual transmission risk—transmission can occur even without visible lesions 3, 4
• Recommend consistent latex condom use, which reduces HSV-2 transmission from women to men and men to women 3
• Advise avoiding sexual contact when partner has overt genital or orolabial lesions 3

Treatment options for asymptomatic patients:

• Suppressive therapy consideration: Valacyclovir 500 mg once daily reduces HSV-2 transmission to susceptible heterosexual partners by 50% 3
• No treatment: Acceptable for asymptomatic individuals who are not in serodiscordant relationships 2
• Counsel sex partners to undergo type-specific serologic testing to determine if they are at risk for HSV-2 acquisition 4

For Symptomatic Patients (Active or Recurrent Genital Herpes)

First clinical episode:

• Valacyclovir 1 gram orally twice daily for 7-10 days 2
• Initiate treatment as soon as possible—there are no data on effectiveness when treatment starts >72 hours after symptom onset 4

Recurrent episodes (episodic therapy):

• Valacyclovir 500 mg orally twice daily for 5 days 2
• Patients should initiate therapy at first sign or symptom of recurrence (prodrome, tingling, itching) 4
• No data support effectiveness when treatment starts >24 hours after symptom onset for recurrent episodes 4

Chronic suppressive therapy (for frequent recurrences):

• Valacyclovir 1 gram orally once daily 2
• Reduces recurrence frequency and improves quality of life 2
• Reduces transmission risk by 50% 3
• Safety beyond 1 year in immunocompetent patients has not been established 2
• No laboratory monitoring needed unless substantial renal impairment exists 2

Special Populations

HIV-Infected Patients

• Routine type-specific HSV-2 serologic testing should be performed for all persons seeking HIV care 3, 2
• In profoundly immunocompromised patients (CD4+ <100 cells/µL), extensive, deep, nonhealing ulcerations may occur and are more commonly associated with acyclovir-resistant virus 3
• Higher antiviral doses may be needed for severe mucocutaneous lesions 2
• Safety of chronic suppressive therapy beyond 6 months in HIV-infected patients has not been established 4

Pregnant Women

• Screening for HSV-2 is not recommended in pregnant women, except for those at risk of acquiring HSV near delivery 2
• Type-specific serology can help identify women at risk for primary infection during pregnancy 3

Key Clinical Pearls

• HSV-2 has higher recurrence rates and more frequent subclinical shedding than HSV-1 genital infections 1
• Valacyclovir is not a cure—patients must understand this is lifelong viral suppression 4
• Common adverse events include nausea and headache 2
• Patients should maintain adequate hydration while on therapy 4
• Critical limitation: Commercial HSV-2 serologic tests cannot determine the etiology of a presenting genital lesion with certainty—viral culture, HSV DNA PCR, or antigen detection from lesions is required for definitive diagnosis of active infection 3, 1