What is the most likely diagnosis and appropriate antiviral management for a woman with a vaginal lesion who tests positive for herpes simplex virus type 2 immunoglobulin G (HSV‑2 IgG)?

Diagnosis and Management of Vaginal Lesion with Positive HSV-2 IgG

The most likely diagnosis is recurrent genital HSV-2 infection, and the patient should receive antiviral therapy with either valacyclovir 500 mg orally twice daily for 5 days (episodic therapy) or valacyclovir 1 g orally once daily (suppressive therapy), depending on recurrence frequency and patient preference. 1

Diagnostic Interpretation

The presence of a vaginal lesion combined with positive HSV-2 IgG antibodies indicates established HSV-2 infection with a current clinical recurrence. 1 However, critical diagnostic steps remain:

Confirm Active Infection from the Lesion

• Nucleic acid amplification testing (NAAT/PCR) from the lesion is the gold standard diagnostic test, with >90% sensitivity and specificity, and should be performed to confirm HSV is causing the current lesion. 2, 3
• PCR testing can differentiate HSV-1 from HSV-2 and provides results in approximately 2 hours. 3
• Viral culture is acceptable if PCR is unavailable, though it has lower sensitivity (particularly for healing lesions). 2
• Direct immunofluorescence and Tzanck smear should NOT be used due to inadequate sensitivity and specificity. 2, 3

Understanding the Serology Result

• The positive HSV-2 IgG confirms chronic HSV-2 infection but does not prove the current lesion is caused by HSV-2—it only indicates past infection. 2
• HSV-2 IgG antibodies persist indefinitely after infection and cannot distinguish between active and latent infection. 2
• Serologic testing alone cannot determine the etiology of a presenting genital lesion with certainty. 2

Treatment Approach

The management strategy depends on whether this is a first recognized episode versus a known recurrent pattern:

For Episodic Therapy (Treating Individual Recurrences)

Recommended regimens (choose one): 1

• Valacyclovir 500 mg orally twice daily for 5 days
• Acyclovir 400 mg orally three times daily for 5 days
• Famciclovir 125 mg orally twice daily for 5 days

Key points:

• Episodic therapy is most effective when started during prodromal symptoms or within 1 day of lesion onset. 1
• Treatment duration may be extended if healing is incomplete after the initial course. 1

For Suppressive Therapy (Daily Prevention)

Suppressive therapy should be offered if the patient has ≥6 recurrences per year: 1

Recommended regimens (choose one): 1

• Valacyclovir 1 g orally once daily
• Acyclovir 400 mg orally twice daily
• Famciclovir 250 mg orally twice daily

Benefits of suppressive therapy:

• Reduces recurrence frequency by ≥75%. 1
• Decreases asymptomatic viral shedding from 10.8% to 2.9% of days. 4
• Reduces HSV-2 transmission to uninfected partners by approximately 48-50%. 4, 1

If This is the First Recognized Episode

Even with positive HSV-2 IgG (indicating prior infection), if this is the patient's first clinically recognized outbreak, treat as a first clinical episode: 1

• Valacyclovir 1 g orally twice daily for 7-10 days
• Acyclovir 400 mg orally three times daily for 7-10 days
• Famciclovir 250 mg orally three times daily for 7-10 days

Critical Counseling Points

Natural History Education

• Approximately 50% of women with HSV-2 antibodies initially report no history of genital lesions but develop recognizable symptoms after proper education about what to look for. 5
• Most HSV-2 infections are unrecognized—only 13% of HSV-2 seropositive persons have been diagnosed. 2, 1
• Transmission occurs most commonly during asymptomatic periods when no lesions are visible. 4

Transmission Prevention

• Abstain from sexual activity when lesions or prodromal symptoms are present. 1
• Consistent condom use reduces but does not eliminate transmission risk. 4
• Daily suppressive valacyclovir 500 mg reduces transmission to uninfected partners by 48-50%. 4
• Even with condoms and suppressive therapy, transmission can still occur. 4

Partner Management

• Inform all sexual partners about HSV-2 status. 1
• HSV-2 infection increases HIV acquisition risk 3-fold. 2, 4
• Uninfected partners should consider type-specific serologic testing. 4

Common Pitfalls to Avoid

• Do not assume the lesion is HSV without virologic confirmation—other causes of genital ulcers must be excluded, particularly in high-risk populations. 2
• Do not rely on episodic therapy to reduce transmission risk—only daily suppressive therapy has this effect. 4
• Do not assume avoiding sex during visible outbreaks eliminates transmission risk—the majority of transmission occurs during asymptomatic shedding. 4
• If the patient is of childbearing age, ensure obstetric providers are informed of HSV-2 status during any pregnancy due to neonatal infection risk. 4, 6