What does a positive herpes Immunoglobulin G (IgG) result indicate and what treatment is necessary?

Positive Herpes IgG: Interpretation and Management

A positive herpes IgG antibody test indicates past exposure and ongoing latent infection with HSV, with antibodies persisting indefinitely after infection, but treatment is only necessary if the patient has symptomatic outbreaks or wishes to reduce transmission risk to sexual partners. 1

Critical Test Interpretation Issues

The interpretation of a positive HSV IgG result requires careful attention to several key factors:

Index Value Matters Significantly

• For HSV-2 IgG results with index values <3.0, confirmatory testing with a second assay using a different glycoprotein G antigen is strongly recommended before delivering results to the patient. 2
• Index values of 1.1-2.9 have only 39.8% specificity, meaning a high rate of false positives in this range. 2
• Index values ≥3.0 have improved specificity of 78.6% and may be sufficient for diagnosis without confirmatory testing, though false positives can still occur even above 3.5. 2
• Using the Biokit HSV-2 rapid assay as confirmatory testing improves specificity from 93.2% to 98.7% compared to Western blot, and increases positive predictive value from 80.5% to 95.6%. 2

False Positives Are Common in Certain Populations

• Individuals with HSV-1 infection are significantly more likely to have false-positive HSV-2 tests, particularly with low index values. 2
• This is a critical pitfall in clinical practice, as HSV-1 seropositivity is extremely common in the general population. 2

Timing and Window Period

• A negative result within 12 weeks of potential exposure may represent the "window period" before antibodies develop, and testing should be repeated at 12 weeks post-exposure if recent acquisition is suspected. 2, 1
• The sensitivity of HSV-2 serologic testing is 92%, with false-negatives occurring primarily during this window period. 2

What the Test Does and Does Not Tell You

What It Indicates

• The test confirms past exposure and ongoing latent infection, but does NOT distinguish between recent and long-standing infections. 1
• Type-specific IgG antibodies develop within several weeks of infection and persist for life. 1
• HSV-2 is primarily associated with genital herpes and has higher rates of symptomatic recurrences and subclinical viral shedding compared to HSV-1 genital infections. 1

What It Cannot Determine

• Serological tests alone cannot determine the etiology of a presenting genital lesion with certainty. 2, 3
• The test does not predict whether the patient will have symptomatic outbreaks or remain asymptomatic. 1
• IgM testing is NOT reliable for distinguishing recent from past infection, as approximately one-third of patients with recurrent genital herpes have IgM responses. 2

Treatment Decisions Based on Clinical Scenario

Asymptomatic Patients (No Active Lesions)

For asymptomatic patients with positive HSV IgG, treatment is NOT routinely indicated unless the patient wishes to reduce transmission risk to sexual partners. 1, 3

• Counseling should address the natural history of disease, potential for recurrent episodes, asymptomatic viral shedding, and sexual transmission risk. 3
• Patients should be advised to abstain from sexual activity while lesions are present if they develop symptoms. 3
• Condom use should be encouraged during all sexual exposures, as transmission can occur during asymptomatic periods. 3

Symptomatic Patients with Recurrent Outbreaks

Two treatment approaches are available: episodic therapy for individual outbreaks or suppressive therapy to reduce recurrence frequency and transmission risk. 2, 1

• Dosing strategies that are most feasible for patient adherence should be prioritized. 2
• The same medication dosages and frequencies are recommended for both genital HSV-1 and HSV-2 infections. 2, 3
• Treatment options include acyclovir, famciclovir, and valacyclovir, with multiple FDA-approved regimens available. 2

Special Populations Requiring Consideration

• Pregnant women at risk of acquiring HSV close to delivery should undergo type-specific serology. 2, 4, 3
• Men who have sex with men and people who are HIV positive should be offered type-specific serology. 2, 4, 3
• HIV-infected persons may require intermittent or suppressive therapy at increased dosages. 3
• Individuals with severe immunosuppression (such as bone marrow transplant recipients) with positive HSV serology should receive acyclovir or congeners prophylactically due to high risk of reactivation. 2

Key Clinical Pitfalls to Avoid

Do Not Screen Asymptomatic Low-Risk Populations

• The USPSTF recommends against screening for HSV-2 infection among asymptomatic adolescents and adults. 2, 3
• Widespread screening for HSV antibodies should be discouraged due to test limitations and the potential for false-positive results causing unnecessary anxiety. 2, 4, 3
• Screening of pregnant women is not recommended. 2

Do Not Rely on Low Index Values Without Confirmation

• Delivering results to patients based on low positive index values (<3.0) without confirmatory testing leads to misdiagnosis in a substantial proportion of cases. 2, 1
• This is particularly problematic in low-prevalence populations where positive predictive value is reduced. 2

Do Not Use Serology Alone for Active Lesions

• For patients presenting with active genital lesions, NAAT/PCR from the lesion is the first-line diagnostic test, not serology. 4, 3
• Serological tests cannot inform the etiology of a presenting genital lesion with certainty. 2, 3