What is the treatment for a patient with positive Herpes Simplex (HSV) Immunoglobulin M (IgM) and Immunoglobulin G (IgG) results, indicating both current and past infection?

Management of Positive HSV IgM and IgG Serology

The presence of both HSV IgM and IgG antibodies does not reliably distinguish between primary and recurrent infection, and treatment decisions should be based on clinical presentation rather than serology alone, as IgM can be detected in approximately one-third of patients with recurrent HSV-2 infections. 1

Understanding Your Serological Results

Critical Limitation of IgM Testing:

• HSV-specific IgM is a poor indicator of recent infection because approximately 33% of patients with recurrent genital herpes caused by HSV-2 demonstrate IgM responses, making it unreliable for distinguishing new from reactivated infection 1
• IgG antibodies develop within the first several weeks after infection and persist indefinitely, indicating past exposure and ongoing latent infection 1
• Serological tests alone cannot determine the cause of a presenting genital lesion with any degree of certainty 1

Important Caveat:

• False-positive IgM results can occur, particularly in the context of other herpesvirus infections (such as VZV), so clinical correlation is essential 2

Treatment Algorithm Based on Clinical Presentation

If You Have Active Lesions (Vesicles, Ulcers, or Prodromal Symptoms):

First Clinical Episode:

• Valacyclovir 1 g orally twice daily for 7-10 days 3
• Alternative: Acyclovir 400 mg orally three times daily for 7-10 days 1, 4
• Alternative: Famciclovir 125 mg orally twice daily for 5 days 3
• Start treatment immediately—do not wait for confirmatory testing, as antiviral efficacy decreases significantly when initiated after 72 hours of symptom onset 3

Recurrent Episodes:

• Valacyclovir 500 mg orally twice daily for 5 days, starting at the first sign of prodrome 3
• Alternative: Acyclovir 400 mg orally three times daily for 5 days 3
• Alternative: Famciclovir 125 mg orally twice daily for 5 days 3

If You Have Frequent Recurrences (≥6 Episodes Per Year):

Daily Suppressive Therapy:

• Valacyclovir 500 mg once daily continuously reduces recurrence frequency by ≥75% 3
• Alternative: Acyclovir 400 mg orally twice daily 1
• Continue suppressive therapy for at least 1 year, then discontinue to reassess recurrence rate 1
• Maintain BsAb dosing if applicable during suppressive therapy 1

If You Are Asymptomatic:

No Treatment Required:

• Positive serology in the absence of symptoms indicates latent infection that does not require antiviral therapy 1
• Counseling is essential regarding natural history, potential for recurrent episodes, asymptomatic viral shedding (which occurs even without visible lesions), and sexual transmission risk 1, 5
• Sexual partners should be informed and offered type-specific serological testing 5

Confirmatory Testing Recommendations

If Active Lesions Are Present:

• Nucleic acid amplification testing (NAAT/PCR) from the lesion is the first-line diagnostic test, with sensitivity and specificity exceeding 90% and offering 11-71% superior sensitivity compared to viral culture 5
• Optimal sampling includes collecting fluid from intact vesicles or swabbing the base of ulcers 5
• HSV type determination (HSV-1 vs HSV-2) is important for counseling and prognosis, as genital HSV-1 has much less frequent recurrences than genital HSV-2 1

If Serological Confirmation Is Needed:

• For low positive HSV-2 IgG results (index value <3.0), confirm with a second test using a different glycoprotein G antigen to avoid false-positive results, as specificity is only 57.4% overall and 39.8% for index values 1.1-2.9 1, 5
• Index values ≥3.0 have 78.6% specificity and may be sufficient for diagnosis without further confirmatory testing 1
• If negative serology occurred within 12 weeks of potential exposure, repeat testing after 12 weeks to account for the antibody window period 1, 5

Special Populations Requiring Attention

Immunocompromised Patients:

• If serologic tests for HSV are positive and the patient is undergoing immunosuppressive therapy (such as bone marrow transplantation, bispecific antibody therapy, or radiation), acyclovir or valacyclovir prophylaxis should be administered to prevent reactivation 1
• Acyclovir or valacyclovir prophylaxis is recommended for all relapsed/refractory multiple myeloma patients receiving treatment 1
• Prophylaxis should be maintained while the patient is receiving treatment, and thereafter at the discretion of the individual physician 1

Pregnant Women:

• Type-specific HSV-2 serology is recommended for pregnant women at risk of acquiring HSV infection close to delivery 1, 5

HIV-Positive Patients and Men Who Have Sex With Men:

• Type-specific serology should be used for detecting asymptomatic individuals in these high-risk populations 1, 5

Common Pitfalls to Avoid

• Do not rely on IgM results alone to determine whether infection is primary or recurrent, as this leads to misdiagnosis in one-third of recurrent cases 1
• Do not use topical acyclovir, as it is substantially less effective than oral therapy 1, 3
• Do not delay treatment waiting for confirmatory testing if lesions are present, as efficacy decreases significantly after 72 hours 3
• Do not pursue widespread screening for HSV antibodies in asymptomatic general populations, as this is discouraged due to potential for false-positive results and limited clinical utility 1, 5
• Do not use unproven supplements such as lysine instead of evidence-based antivirals, as this delays effective treatment and allows lesions to progress 3