Can a positive Herpes Simplex Virus 1 (HSV1) result cause a false positive for Herpes Simplex Virus 2 (HSV2)?

HSV-1 Infection Can Cause False Positive HSV-2 Test Results

Yes, being positive for HSV-1 can cause false positive results on HSV-2 serologic tests, particularly when using enzyme immunoassay (EIA) or chemiluminescent immunoassay (CLIA) tests with low index values. 1

Understanding HSV Serologic Testing

Test Characteristics and Limitations

• Type-specific serologic tests differentiate between HSV-1 and HSV-2 by detecting antibodies to HSV glycoprotein G-1 (gG-1) or glycoprotein G-2 (gG-2) 1, 2
• Gold standard: Western blot/immunoblot assays that target antibodies to several HSV antigens 1
• Common commercial tests: Enzyme immunoassay (EIA) and chemiluminescent immunoassay (CLIA) 1

Cross-reactivity Issues

• Persons with HSV-1 infection are more likely to have false-positive HSV-2 test results with low index values compared to those without HSV-1 infection 1
• The specificity of HSV-2 serologic tests is particularly poor at low index values:
  • Index values 1.1-2.9: only 39.8% specificity
  • Index values ≥3.0: improved to 78.6% specificity 1

Improving Diagnostic Accuracy

Confirmatory Testing Strategy

When a patient tests positive for HSV-2 (especially with low index values <3.0):

1. Confirm with a second test using a different gG antigen 1
2. Consider Biokit HSV-2 rapid assay as a confirmatory test:
   • Improves specificity of HerpeSelect from 93.2% to 98.7% compared to Western blot
   • Increases positive predictive value from 80.5% to 95.6% 1, 3
3. Western blot can be used if Biokit is unavailable (though access may be limited) 1

Index Value Interpretation

• Index value ≥3.0: May be sufficient for diagnosis without further confirmatory testing
• Index value <3.0: Should ideally be confirmed with a second test 1, 2
• Be cautious: False positives have been reported even with index values >3.5 1

Clinical Implications and Pitfalls

Potential for Misdiagnosis

• False-negative results can occur in 12-30% of patients with recurrent HSV-1 or HSV-2 DNA positive genital lesions 4
• Previous HSV-1 infection increases the likelihood of asymptomatic HSV-2 seroconversion by a factor of 2.6 5

Best Practices for Testing

• Nucleic acid amplification testing (NAAT/PCR) from active lesions is the gold standard for diagnosis of active HSV infections 2
• Wait at least 12 weeks after suspected exposure before conducting serologic tests (window period) 1, 2
• Avoid HSV direct immunofluorescence assay and Tzanck smear due to lack of sensitivity 1, 2

When to Consider Serologic Testing

• Asymptomatic individuals with high-risk exposures
• Pregnant women at risk of acquiring HSV near delivery
• Men who have sex with men
• HIV-positive individuals 2

Remember that HSV-2 is a chronic, lifelong infection that impacts sexual health, making accurate diagnosis paramount. The potential for false positive results due to HSV-1 cross-reactivity highlights the importance of confirmatory testing, particularly when index values are low.