HSV Index Value Calculation and Interpretation
The index value for HSV serologic testing is not calculated by clinicians—it is automatically generated by the laboratory's enzyme immunoassay (EIA) or chemiluminescent immunoassay (CLIA) equipment as a quantitative measure of antibody present in the patient's serum. 1
Understanding the Index Value System
The index value is a laboratory-generated numerical result that reflects antibody concentration:
- Index value <0.9: Negative result 1
- Index value 0.9-1.1: Indeterminate result 1
- Index value >1.1: Positive result per manufacturer's label 1
However, this manufacturer cutoff is clinically problematic and should not be used without further interpretation. 1
Critical Clinical Interpretation Based on Index Values
For HSV-2 testing, the index value dramatically affects test accuracy and should guide your clinical decision-making:
- Index values 1.1-2.9: Only 39.8% specificity—meaning more than half of these "positive" results are false positives 1, 2
- Index values ≥3.0: Improved specificity of 78.6%, but still not perfect 1, 2
- False positives occur even at index values >3.5 with FDA-approved assays 1
The risk of false-positive HSV-2 results is significantly higher in patients who have HSV-1 antibodies, particularly at low index values. 1, 2
Algorithmic Approach to Managing Index Values
Step 1: Order type-specific HSV-2 IgG testing using glycoprotein G-based EIA or CLIA 3
Step 2: Interpret results based on the index value:
If index value <0.9: Negative result, but remember the 12-week window period—retest after 12 weeks if recent exposure is suspected 1, 2
If index value 0.9-1.1: Indeterminate—requires repeat testing or confirmatory testing 1
If index value 1.1-2.9: Low positive—mandatory confirmation with a second assay using a different glycoprotein G antigen before reporting results to the patient 1, 2
If index value ≥3.0: May be sufficient for diagnosis without confirmatory testing, though false positives still occur 1
Step 3: For low-positive results (index value <3.0), confirm with:
- Biokit HSV-2 rapid assay (preferred): Improves specificity from 93.2% to 98.7% and positive predictive value from 80.5% to 95.6% 1, 2
- Western blot (if Biokit unavailable): Gold standard but limited availability 1, 3
Common Pitfalls to Avoid
Never report low-positive HSV-2 results (index value <3.0) without confirmation—this leads to false-positive diagnoses with devastating psychological and relationship consequences for patients. 1, 3
Do not test within 12 weeks of potential exposure—the window period can extend up to 12 weeks, and testing earlier will miss recent infections. 1, 2
Do not use HSV-1 serology for clinical decision-making—commercial HSV-1 assays have only 70.2% sensitivity, resulting in frequent false-negative results. 1, 4
Do not order serology when active lesions are present—use NAAT/PCR on the lesion instead, which has >90% sensitivity and specificity. 1, 3
Test Performance Characteristics
The overall sensitivity of HSV-2 serologic testing is 92%, but specificity varies dramatically by index value as noted above. 1 Recent comparative studies confirm that not all FDA-approved assays perform equally—some platforms have positive predictive values as low as 69% for HSV-2 at population-level seroprevalence. 5