What are the diagnostic and treatment approaches for Herpes Simplex Virus 2 (HSV 2) infection?

HSV-2 Diagnosis

For active genital lesions, nucleic acid amplification testing (NAAT/PCR) from the lesion is the first-line diagnostic test, offering superior sensitivity (>90%) compared to viral culture, and all detected virus should be typed to distinguish HSV-1 from HSV-2 for accurate prognostic counseling. 1, 2

Diagnostic Approach for Active Lesions

First-Line Testing: NAAT/PCR

• NAAT/PCR is the preferred diagnostic method for genital ulcers or lesions, with 11-71% superior sensitivity compared to viral culture and >90% sensitivity and specificity for most FDA-approved assays. 1, 2
• Optimal sampling technique involves collecting fluid from intact vesicles or swabbing the base of ulcers. 2
• Type-specific testing to differentiate HSV-1 from HSV-2 is essential because genital HSV-1 recurs less frequently than genital HSV-2, affecting long-term management and counseling. 1

Second-Line Testing: Viral Culture

• If NAAT is unavailable due to cost or laboratory limitations, viral culture is reasonable but has significantly lower sensitivity, particularly as lesions heal. 1, 2
• If HSV culture is negative but clinical suspicion remains high, proceed to type-specific serology to rule out HSV-2 infection. 1

Tests to Avoid

• HSV direct immunofluorescence assay and Tzanck smear lack sensitivity and should not be used for diagnosis. 1

Serologic Testing Strategy

When to Use Serology

• Type-specific HSV-2 serology should be obtained for patients with genital symptoms consistent with herpes (classic or atypical) when lesions are absent or healed. 1, 2
• Serology is appropriate for patients previously told they have genital herpes without virologic confirmation. 1
• Consider serologic screening for high-risk populations including pregnant women at risk of acquiring HSV near delivery, men who have sex with men, HIV-positive individuals, and sexual partners of known HSV-2-positive persons. 1, 2

Critical Limitations of Serologic Testing

• HSV-2 EIA/CLIA assays have poor specificity, particularly at low index values (1.1-2.9), with only 39.8% specificity in this range and 57.4% overall specificity compared to Western blot. 1
• For index values <3.0, confirm positive results with a second assay using a different glycoprotein G antigen (such as Biokit HSV-2 rapid assay) before disclosing results to patients. 1, 2
• Combining HerpeSelect with Biokit confirmatory testing improves positive predictive value from 80.5% to 95.6%, with greatest impact in low-prevalence populations. 1
• Index values ≥3.0 may be sufficient for diagnosis without confirmatory testing, though false positives have been reported even at values >3.5. 1

Window Period Considerations

• The window period for HSV-2 antibody development is up to 12 weeks; do not repeat serologic testing until 12 weeks after exposure to determine if HSV-2 was acquired. 1, 2
• Sensitivity of HSV-2 serology is high at 92%, but false-negatives occur during the window period. 1

Screening Recommendations

• Routine screening of asymptomatic individuals with low pretest probability (few lifetime partners, no known HSV-2-positive partners, no genital symptoms) is not recommended. 1
• Screening of pregnant women for HSV-2 is not recommended. 1

Common Diagnostic Pitfalls

Critical Errors to Avoid

• Never rely on clinical diagnosis alone—most genital herpes presents with mild, atypical lesions that cannot be accurately diagnosed by physical examination, and laboratory confirmation is essential. 1
• Do not obtain HSV molecular assays in the absence of genital ulcers; intermittent viral shedding makes this approach insensitive. 1
• Persons with HSV-1 infection are more likely to have false-positive HSV-2 serology at low index values. 1
• In profoundly immunocompromised patients (CD4+ <100 cells/µL), expect extensive, deep, nonhealing ulcerations that may be associated with acyclovir-resistant virus. 1

Post-Diagnosis Counseling Requirements

• All HSV-2 diagnoses must be accompanied by counseling about transmission risk to sexual partners, natural history of disease, potential for recurrent episodes, and asymptomatic viral shedding. 1, 2, 3

Treatment Considerations

First Clinical Episode

• Acyclovir 400 mg orally three times daily for 7-10 days 4, 3
• Valacyclovir 1 g orally twice daily for 7-10 days 4, 3
• Famciclovir 250 mg orally three times daily for 7-10 days 4

Recurrent Episodes (Episodic Therapy)

• Valacyclovir 500 mg orally twice daily for 5 days is preferred for episodic therapy, most effective when started during prodrome or within 1 day of lesion onset. 4, 3
• Alternative: Acyclovir 800 mg orally twice daily for 5 days 4

Suppressive Therapy (≥6 recurrences/year)

• Valacyclovir 1 g orally once daily 4, 3
• Alternative: Acyclovir 400 mg orally twice daily 4, 3

Critical Treatment Pitfalls

• Topical acyclovir is substantially less effective than oral systemic drugs and should not be used for genital herpes. 4, 3
• Never prescribe topical corticosteroids for HSV infection—they potentiate viral replication and worsen disease. 4
• Avoid treating based solely on positive serology without clinical symptoms. 3