How is Herpes Simplex Virus (HSV) confirmed and treated?

Diagnosis and Treatment of Herpes Simplex Virus (HSV)

Nucleic acid amplification tests (NAATs) such as PCR are the gold standard for confirming HSV infection from active lesions, offering superior sensitivity and specificity compared to other diagnostic methods. 1, 2

Diagnostic Approach for HSV

First-Line Testing for Symptomatic Patients

• NAAT/PCR is the preferred diagnostic test for patients with active genital lesions, with sensitivity 11-71% higher than viral culture 2, 1
• PCR allows simultaneous detection and typing of HSV-1 and HSV-2 in a single reaction, which is crucial for proper counseling and prognosis 2, 1
• Most FDA-approved HSV PCR assays have >90% sensitivity and specificity for detecting HSV from clinical specimens 2
• Samples should be collected from fluid in intact vesicles or the base of ulcers for optimal results 1

Alternative Testing Options

• Viral culture is the second choice if NAAT/PCR is unavailable, though it has lower sensitivity, especially for healing lesions 2
• Antigen detection methods (direct immunofluorescence or enzyme immunoassay) may be used if NAAT or culture is unavailable, but HSV type determination remains important 2, 1
• HSV direct immunofluorescence assay and Tzanck smear lack sensitivity and are not recommended for diagnosis 2, 1

Serologic Testing

• Type-specific serology should only be used for:

  • Detecting asymptomatic individuals at high risk 2
  • Testing pregnant women at risk of acquiring HSV near delivery 2
  • Men who have sex with men and people who are HIV positive 2
  • When genital symptoms are present but direct testing of lesions is negative or lesions have healed 2

• Widespread screening for HSV antibodies is discouraged 2

Important Diagnostic Considerations

HSV Type Differentiation

• Differentiating between HSV-1 and HSV-2 is essential as they have different prognostic implications 1, 2
• HSV-2 is primarily associated with genital disease, while HSV-1 can cause both oropharyngeal and genital infections 2
• Recurrences and subclinical viral shedding are less frequent with genital HSV-1 than HSV-2 1

Limitations of Serologic Testing

• HSV-1 serologic assays lack sensitivity (approximately 70.2%), which can result in false-negative diagnoses 2
• HSV-2 serologic tests lack specificity, particularly at lower index values 2
• For HerpeSelect HSV-2 assay, index values of 1.1-2.9 have only 39.8% specificity, while values ≥3.0 have 78.6% specificity 2
• False-negative tests may occur during the window period (up to 12 weeks after infection) 2

Improving Serologic Test Accuracy

• Confirm low positive HSV-2 results (index value <3.0) with a second assay using a different gG antigen 2
• Using Biokit HSV-2 rapid assay as a confirmatory test improves HerpeSelect specificity from 93.2% to 98.7% 2
• Western blot/immunoblot assays are the gold standard for HSV serologic testing but have limited availability 2

Treatment Approach

First Clinical Episode

• Valacyclovir 1g orally twice daily for 7-10 days 3, 4
• Alternative: Acyclovir 400mg orally three times daily for 7-10 days 3
• Alternative: Famciclovir with appropriate dosing 5, 3

Recurrent Episodes

• Valacyclovir 500mg orally twice daily for 5 days 3
• For frequent recurrences, suppressive therapy with valacyclovir 1g or 500mg orally once daily 3, 4

Special Populations

• HIV-infected patients require higher doses of antivirals 3
• Pregnant women should discuss safety considerations with their healthcare provider 3

Common Pitfalls to Avoid

• Do not rely solely on clinical diagnosis without laboratory confirmation 1, 6
• Do not use HSV molecular assays in the absence of genital ulcers due to intermittent viral shedding 2, 1
• Avoid treating based solely on positive serology without clinical symptoms 3
• Do not delay treatment beyond 72 hours of symptom onset as this significantly reduces effectiveness 3
• Topical acyclovir is substantially less effective than oral therapy and is not recommended 3