HSV Serology: IgG vs IgM Testing Strategy
Direct Answer
Order HSV type-specific IgG serology (not IgM) for diagnosing past HSV infection in asymptomatic patients or those without active lesions, and IVIG cannot replace antiviral therapy for HSV—it only addresses hypogammaglobulinemia as a separate risk factor. 1, 2
When to Order Each Test
HSV IgG Testing (The Preferred Serologic Test)
Use type-specific HSV-2 IgG serology using glycoprotein G-based assays in these specific scenarios:
High-risk populations requiring screening: 1
Patients without active lesions who need diagnostic clarification 3
Interpretation: IgG antibodies develop within several weeks after infection and persist indefinitely, indicating past exposure and ongoing latent infection 2. The test cannot distinguish between recent and long-standing infections 1.
HSV IgM Testing (Limited Clinical Utility)
IgM testing is NOT recommended for routine screening or diagnosis because: 2
- Approximately 33% of patients with recurrent HSV-2 infections demonstrate IgM responses, making it unreliable for distinguishing new from reactivated infection 2, 4
- IgM has only 79% sensitivity and 85% negative predictive value 4
- IgM antibodies may take up to 10 days to develop 4
- The presence of both IgM and IgG does not reliably distinguish primary from recurrent infection 2
The only potential use: IgM may provide some indication of recent infection in select cases, but treatment decisions should be based on clinical presentation rather than serology alone 2, 4.
Critical Testing Pitfalls to Avoid
The Window Period Problem
- A negative IgG result within 12 weeks of potential exposure may represent the "window period" and should be repeated after 12 weeks if recent acquisition is suspected 1
False Positive Results
- Index values of 1.1-2.9 have only 39.8% specificity (60% false positives) 1
- Index values ≥3.0 have 78.6% specificity (21% false positives) 1
- For low positive results (index value <3.0), confirm with a second test using a different glycoprotein G antigen 1
- Patients with HSV-1 infection are more likely to have false-positive HSV-2 tests with low index values 1
Wrong Test for the Clinical Situation
- Never perform HSV molecular assays (PCR/NAAT) in the absence of genital ulcers—due to intermittent shedding, swabs without lesions are insensitive and unreliable 1, 3
- For active lesions, use PCR/NAAT from the lesion as first-line diagnostic test (sensitivity and specificity exceeding 90%) 3, 2
IVIG and HSV: Addressing the Misconception
IVIG Does NOT Replace Antiviral Therapy
IVIG is indicated for hypogammaglobulinemia, not for HSV treatment: 5
- IVIG replacement therapy is recommended for patients with IgG levels <400 mg/dL 5
- IVIG is given for patients with ≥2 severe recurrent infections by encapsulated bacteria, regardless of IgG level 5
- IVIG is used for life-threatening infections or documented bacterial infections with insufficient response to antibiotics 5
Critical distinction: IgG and IgM serology tests for diagnosis of past viral infections may be used routinely in hypogammaglobulinemic patients, but must be interpreted with caution because patients often receive IVIG treatment, which may impact the results 5. Patients may also have false negative results due to failure to mount antibody responses to pathogens 5.
HSV Treatment Remains Antiviral-Based
For HSV infections, regardless of IgG status: 2
- First clinical episode: Valacyclovir 1 g orally twice daily for 7-10 days 2
- Recurrent episodes: Valacyclovir 500 mg orally twice daily for 5 days 2
- Frequent recurrences (≥6 episodes/year): Daily suppressive therapy with valacyclovir 500 mg once daily reduces recurrence frequency by ≥75% 2
- Immunocompromised patients: Acyclovir or valacyclovir prophylaxis to prevent reactivation 2
Treatment should start immediately without waiting for confirmatory testing, as antiviral efficacy decreases significantly when initiated after 72 hours of symptom onset 2.
Screening Recommendations
Do NOT Screen the General Population
- The US Preventive Services Task Force recommends against routine serologic screening for HSV-2 infection in asymptomatic adolescents and adults (Grade D recommendation) 1
- Widespread screening is discouraged due to potential for false-positive results and limited clinical utility 2
Screen Only High-Risk Groups
As outlined above, limit type-specific HSV-2 IgG serology to pregnant women at risk near delivery, MSM, HIV-positive individuals, and partners of known HSV patients 1.