Which test result is more reliable for diagnosing Herpes Simplex Virus (HSV) infection, a positive Immunoglobulin G (IgG) test indicating past exposure or a negative HSV Type 1&2 DNA qualitative real-time Polymerase Chain Reaction (PCR) test indicating no current viral replication, in a patient with a history of positive IgG results for both HSV 1&2 and a subsequent negative PCR result 7 days later?

Believe the Positive IgG Antibody Test

The positive HSV-1 and HSV-2 IgG antibody test is the correct result to believe, as it indicates established infection with both viral types, while the negative PCR test simply reflects the absence of active viral replication at the time of sampling—not the absence of infection. 1, 2

Understanding Why These Results Are Not Contradictory

The two tests measure fundamentally different aspects of HSV infection:

• IgG serology detects antibodies that develop within several weeks of infection and persist indefinitely for life, indicating past exposure and ongoing latent infection 2
• PCR detects viral DNA only when the virus is actively replicating and shedding, which occurs intermittently during outbreaks or asymptomatic shedding episodes 3, 4

A positive IgG with negative PCR is the expected pattern for someone with established HSV infection who is not actively shedding virus at the moment of testing. 2, 3

Critical Considerations for the IgG Results

Before fully accepting the positive IgG results, you must evaluate the index values from the antibody test:

• Index values ≥3.0 have acceptable specificity (78.6%) and can be considered diagnostic without further confirmation 1, 2
• Index values 1.1-2.9 have poor specificity (only 39.8%) and require confirmatory testing with a second assay using different glycoprotein G antigen 1, 2
• False-positive HSV-2 results are more common in patients with HSV-1 infection, especially at low index values 1, 2

If your patient's HSV-2 index value is <3.0, you should confirm with Biokit HSV-2 rapid assay or Western blot before delivering definitive results, as this improves specificity from 93.2% to 98.7% 1, 2

Why the PCR Test Is Negative

PCR from what appears to be a non-lesional sample (given the 7-day interval and lack of mention of active lesions) would be expected to be negative:

• PCR is the gold standard for diagnosing HSV from active mucocutaneous lesions, with sensitivity and specificity exceeding 90% when sampling vesicular fluid or ulcer bases 3, 4
• PCR cannot detect latent virus residing in nerve ganglia between outbreaks 4
• Viral shedding is intermittent, occurring during symptomatic outbreaks and asymptomatic periods, but not continuously 2, 3

Testing PCR from non-lesional sites or during quiescent periods will be negative despite established infection. 3, 4

Clinical Action Plan

Based on the positive IgG results, proceed as follows:

1. Review the IgG index values from the laboratory report 1, 2

   • If HSV-1 and HSV-2 both ≥3.0: Accept as true positive results
   • If either (particularly HSV-2) is 1.1-2.9: Order confirmatory testing with Biokit assay or Western blot

2. Counsel the patient that they have chronic HSV-1 and HSV-2 infection (pending confirmation if low index values) 2, 3

   • Explain that antibodies persist for life
   • Discuss recurrence patterns (HSV-2 causes more frequent genital recurrences than HSV-1)
   • Address transmission risk and asymptomatic shedding

3. Do not repeat PCR testing unless the patient develops active genital lesions, at which point PCR from the lesion would be appropriate for confirming the cause of that specific outbreak 3

Common Pitfall to Avoid

Do not assume a negative PCR "overrules" a positive IgG test. This represents a fundamental misunderstanding of HSV biology—the virus establishes lifelong latent infection in nerve ganglia, and serologic testing is the appropriate method to diagnose infection in the absence of active lesions. 2, 3, 4