I got a reactive HSV‑1 serology result—what does it indicate, and is any antiviral therapy or further testing needed?

HSV-1 Reactive Serology: Interpretation and Management

What a Reactive HSV-1 Result Means

A reactive (positive) HSV-1 IgG antibody test indicates past exposure and ongoing latent infection with HSV-1, with antibodies persisting indefinitely after infection—this is a marker of chronic infection, not active disease, and does not require antiviral treatment unless you develop symptomatic outbreaks or meet specific high-risk criteria. 1

Key Interpretive Points

• The test cannot distinguish between recent and long-standing infections, as type-specific IgG antibodies develop within several weeks of infection and persist for life 1
• HSV-1 is extremely common, affecting approximately 47.8% of the US population aged 14-49 2
• Most HSV-1 infections are asymptomatic or unrecognized—80-90% of cases progress subclinically but may become symptomatic at any time 2
• The virus establishes lifelong latency in the trigeminal ganglia and remains in a non-multiplying episomal form during latency periods 2

Clinical Significance

Anatomical Distribution

• HSV-1 traditionally manifests above the neck (orolabial herpes), though it can also cause genital infections through oro-genital contact 2
• Among sexually active adults, new genital HSV-1 infections are as common as new oropharyngeal HSV-1 infections 3

Recurrence Patterns

• Genital HSV-1 infections have a more benign natural history with fewer recurrences compared to genital HSV-2, which is critical for counseling 2
• Orolabial herpes presents with a sensory prodrome followed by lesion evolution from papule to vesicle, ulcer, and crust stages on the lips, and can be triggered by sunlight or physiologic stress 2

When Antiviral Therapy IS Indicated

You should receive antiviral therapy (acyclovir or congeners) only in these specific situations:

1. Active Symptomatic Outbreaks

• Episodic therapy for orolabial or genital herpes outbreaks when lesions appear 1
• Treatment should prioritize dosing strategies that are most feasible for adherence 1

2. Severe Immunosuppression

• If you are undergoing bone marrow transplantation or similar immunosuppressive therapy, prophylactic acyclovir or congeners should be administered to prevent HSV reactivation 4
• Patients with positive serologic results are at high risk for reactivation during intense immunosuppression and may present with clinical scenarios mimicking other conditions (e.g., radiation stomatitis) 4

3. Suppressive Therapy (Selected Cases)

• Suppressive therapy may be considered to reduce recurrences and transmission risk in patients with frequent symptomatic outbreaks 1

When Antiviral Therapy IS NOT Indicated

Routine antiviral prophylaxis is NOT recommended for asymptomatic HSV-1 seropositive individuals who are immunocompetent and without active lesions 4, 1

Further Testing Considerations

No Routine Confirmatory Testing Needed

• HSV-1 serologic tests have better sensitivity (70.2%) than HSV-2 tests, though they can still produce false-negatives 4
• If you have no symptoms and are not in a high-risk category, no further testing is required 4, 1

When Additional Testing May Be Warranted

• If you develop genital or oral ulcers, HSV NAAT/PCR from the lesion is the preferred diagnostic test (>90% sensitivity and specificity) to confirm active infection and differentiate HSV-1 from HSV-2 4
• Type determination is important for counseling and prognosis, as it helps predict recurrence patterns 1, 2
• Serological tests alone cannot determine the etiology of a presenting genital lesion with certainty 1

Important Caveats

Test Limitations

• HSV-1 serologic assays lack sensitivity compared to HSV-2 tests, which can result in false-negative diagnoses 4
• The window period may be up to 12 weeks—if recent exposure is suspected and the test is negative, repeat testing after 12 weeks 4, 1

Appropriate Use of Serology

• Widespread screening for HSV antibodies is discouraged 1
• Type-specific serology should be reserved for detecting asymptomatic infections in specific populations (pregnant women at risk of acquiring HSV close to delivery, men who have sex with men, people who are HIV positive) 1

Clinical Pitfalls to Avoid

• Do not obtain HSV molecular assays in the absence of a genital ulcer to diagnose genital herpes infection—due to intermittent viral shedding, swabs obtained without lesions are not sensitive 4
• Do not use HSV direct immunofluorescence assay or Tzanck smear, as they lack sensitivity and are not recommended 4