HSV Testing with Quantitative Results
Order type-specific HSV serologic testing using enzyme immunoassay (EIA) or chemiluminescent immunoassay (CLIA), which provide index values (quantitative antibody measurements) rather than just reactive/non-reactive results. 1
Understanding HSV Serologic Index Values
The commercially available FDA-approved HSV serologic assays provide index values that represent quantitative measures of antibody levels present in the blood 1:
HerpeSelect EIA reports results as index values with the following interpretation per manufacturer's label 1:
- <0.9 = negative
- 0.9–1.1 = indeterminate
1.1 = positive
Index values are the "actual numbers" you're seeking, as they quantify the amount of HSV antibody detected rather than simply reporting reactive/non-reactive 1
Critical Limitations You Must Know
The index value directly impacts test accuracy, particularly for HSV-2 1:
- Index values of 1.1–2.9 have only 39.8% specificity compared to Western blot (meaning high false-positive rate) 1
- Index values of ≥3.0 have 78.6% specificity (still suboptimal but better) 1
- Overall HSV-2 specificity is only 57.4% when compared to the gold standard Western blot 1
For HSV-1 serologic testing, the opposite problem exists - these assays lack sensitivity at only 70.2%, meaning false-negatives are common 1
Recommended Testing Strategy Based on Clinical Scenario
If Active Lesions Are Present:
Do NOT order serology - instead order HSV NAAT/PCR from the lesion, which can provide quantitative viral load results 1, 2, 3:
- PCR assays can quantify HSV DNA copies per mL, giving you actual viral load numbers 3, 4
- One study reported median viral loads of 4.2 × 10⁶ copies/reaction for first-episode infections versus 1.0 × 10⁴ for recurrent infections 3
- PCR has 11-71% superior sensitivity compared to viral culture 2, 5
If No Active Lesions Present:
Order type-specific HSV-1 and HSV-2 serology with index values 1:
- Request the laboratory report the actual index value, not just positive/negative 1
- For HSV-2 results with index values <3.0, confirm with a second assay (Biokit HSV-2 rapid test or Western blot) before informing the patient of positive results 1
- Using confirmatory testing improves positive predictive value from 80.5% to 95.6% 1
- Index values ≥3.0 may be sufficient without confirmatory testing, though false-positives still occur 1
Important Caveats
- Wait 12 weeks after suspected exposure before ordering serology, as the window period can be up to 12 weeks and earlier testing may yield false-negatives 1
- Patients with HSV-1 infection are more likely to have false-positive HSV-2 results with low index values 1
- The Western blot remains the gold standard but has limited availability in most clinical settings 1
What to Order Specifically
Request: "Type-specific HSV-1 and HSV-2 IgG antibody testing by EIA or CLIA with index values reported" and specify that you need the numerical index value, not just a qualitative interpretation 1