Is there a confirmatory test for a patient with a positive Herpes Simplex Virus 2 (HSV 2) result?

Confirmatory Testing for Positive HSV-2 Results

Yes, confirmatory testing is strongly recommended for positive HSV-2 serologic results, particularly when the index value is less than 3.0, using either the Biokit HSV-2 rapid assay or Western blot to avoid false-positive diagnoses that can have significant psychological and relationship consequences. 1

Understanding the Problem with Initial HSV-2 Testing

The commercially available HSV-2 serologic tests (enzyme immunoassay or chemiluminescent immunoassay) have serious specificity limitations that vary dramatically based on the index value reported:

• Index values 1.1-2.9 have only 39.8% specificity, meaning more than half of these results are false positives 1
• Index values ≥3.0 have improved specificity of 78.6%, but false positives still occur even above 3.5 1
• Patients with HSV-1 infection are significantly more likely to have false-positive HSV-2 results, especially at low index values 1

Algorithm for Confirmatory Testing

When to Confirm:

• Always confirm if index value is <3.0 - These results have unacceptably low specificity and should not be reported to patients without confirmation 1, 2
• Consider confirmation even if index value is ≥3.0 in low-prevalence populations or when HSV-1 infection is present, as false positives have been documented even at higher values 1

How to Confirm:

First-line confirmatory test:

• Biokit HSV-2 rapid assay - This uses a different glycoprotein G antigen and improves specificity from 93.2% to 98.7% when combined with HerpeSelect 1, 3
• This combination improves positive predictive value from 80.5% to 95.6%, with greatest impact in low-prevalence populations 1, 3

Alternative confirmatory test:

• Western blot/immunoblot - This is the gold standard for HSV serologic testing, targeting antibodies to multiple HSV antigens beyond glycoprotein G 1, 4
• However, access is limited in most clinical settings 1

Critical Timing Considerations

• Do not test within 12 weeks of potential exposure - The window period for antibody development can be up to 12 weeks, and testing earlier will yield false-negative results 1, 5
• If initial test is negative but recent exposure is suspected, repeat testing after 12 weeks 1, 5

Common Pitfalls to Avoid

• Never report low-positive results (index <3.0) without confirmation - This leads to false-positive diagnoses with devastating psychological consequences for patients 2, 4
• Do not order serology when active genital lesions are present - Use NAAT/PCR from the lesion instead, which has >90% sensitivity and specificity 4, 5
• Do not assume all positive results are true positives - Even with index values >3.5, false positives occur, particularly in patients with HSV-1 infection 1

When Confirmatory Testing May Not Be Necessary

• Index value ≥3.0 in high-prevalence populations may be sufficient for diagnosis without further testing, though providers should remain aware that false positives can still occur 1
• Clinical context matters - In patients with classic recurrent genital symptoms and high pretest probability, higher index values may be more reliable 1, 2

Why This Matters

HSV-2 is a chronic, lifelong infection that impacts sexual health, relationships, and psychological well-being. Accurate diagnosis is paramount before counseling patients about transmission risk, treatment options, and disclosure to partners 1, 2. The consequences of false-positive diagnoses are severe and avoidable with appropriate confirmatory testing strategies.