Can Herpes Simplex Virus 2 (HSV 2) Immunoglobulin G (IgG) test results fluctuate from a high index to a low index?

HSV-2 IgG Index Values Can Fluctuate Between High and Low

Yes, HSV-2 IgG index values can fluctuate from high to low in subsequent tests, as commercial type-specific glycoprotein G HSV-2 antibody assays have significant limitations in reliability and consistency. 1

Understanding HSV-2 Antibody Test Variability

HSV-2 serologic tests measure antibodies to HSV glycoprotein G-2 (gG-2) using various methods:

• Enzyme immunoassay (EIA)
• Chemiluminescent immunoassay (CLIA)
• Western blot/immunoblot (gold standard)

Factors Contributing to Index Value Fluctuations:

1. Test Variability: Commercial tests show inherent variability between testing runs 2

2. Antibody Dynamics:

   • Index values typically rise after infection, peaking around 9-10 weeks post-infection
   • In established infections (even years old), 22% of patients still show at least one low index value 2
   • Some patients experience transient seroreversions where values temporarily drop below positive thresholds 2

3. Antibody Avidity:

   • Antibody binding strength varies over time
   • Lower avidity may contribute to lower index values in established infections 2

4. Test Performance Limitations:

   • False-negative rates of 12-30% occur in patients with recurrent HSV-2 DNA-positive genital lesions 3
   • Even among the best commercial tests, sensitivity and specificity are imperfect 4

Clinical Implications of Fluctuating Index Values

Diagnostic Challenges:

• A single negative or low-positive test cannot definitively rule out HSV-2 infection
• Index values between 1.1-2.9 have particularly poor specificity (only 39.8%) 1
• Values ≥3.0 have better but still imperfect specificity (78.6%) 1

Recommended Testing Approach:

1. For suspected recent infection:

   • Wait at least 12 weeks after potential exposure before testing to avoid false negatives during the "window period" 1

2. For low-positive results (index value <3.0):

   • Confirm with a second assay using a different gG antigen 1
   • Consider supplemental testing with Biokit HSV-2 rapid assay or Western blot 1

3. For established infections with fluctuating results:

   • Consider that even long-standing infections can show variable antibody levels 2
   • Multiple testing may be necessary for accurate diagnosis 3

Pitfalls to Avoid

1. Relying on a single test result: Given the documented fluctuations, multiple tests may be necessary for accurate diagnosis 3

2. Misinterpreting low index values: Low values don't necessarily indicate recent infection or seroreversion 2

3. Using IgM testing: IgM detection is a poor indicator of recent infection as approximately one-third of patients with recurrent genital herpes have IgM responses 1

4. Overinterpreting negative results: False-negative results occur in up to 30% of patients with active HSV-2 infections 3

For accurate diagnosis, consider the clinical presentation alongside serologic testing, and when possible, direct detection methods like PCR from lesions provide more definitive diagnosis during active outbreaks 1.