What is the management for a patient with a reactive Herpes Simplex Virus (HSV) 2 Immunoglobulin G (IgG) test?

Management of HSV-2 Reactive IgG

For a patient with reactive HSV-2 IgG, management depends entirely on symptom status: treat symptomatic patients with oral antivirals, but asymptomatic patients require only counseling—not antiviral therapy. 1, 2

Clinical Assessment Algorithm

Determine if the patient has current or recurrent genital symptoms:

Symptomatic HSV-2 Infection

All symptomatic patients should be offered suppressive therapy as the preferred management approach. 3, 1

First Clinical Episode with Active Lesions

• Valacyclovir 1 g orally twice daily for 7-10 days (preferred regimen) 1
• Alternative: Acyclovir 400 mg orally three times daily for 7-10 days 1
• Alternative: Famciclovir (equivalent dosing) 3
• Treatment must be initiated within 72 hours of symptom onset for maximum effectiveness 1, 2

Recurrent Episodes (Episodic Therapy)

• Valacyclovir 500 mg orally twice daily for 5 days 1
• Alternative: Acyclovir 400 mg orally three times daily for 5 days 3
• Initiate during prodrome or within 24 hours of lesion onset 1, 4
• Episodic therapy does not reduce transmission risk to partners 3

Suppressive Therapy (Preferred for Symptomatic HSV-2)

• Valacyclovir 1 g orally once daily (standard dose) 1
• Alternative: Valacyclovir 500 mg orally once daily (for patients with ≤9 recurrences per year) 1
• Alternative: Acyclovir 400 mg orally twice daily 3
• Suppressive therapy reduces HSV-2 transmission to susceptible heterosexual partners by 50% 3
• After 1 year of continuous suppressive therapy, discontinue to reassess recurrence frequency 2

Asymptomatic HSV-2 Infection

Approximately 20% of HSV-2 seropositive persons do not report genital symptoms. 3

Management Approach

• No antiviral therapy is indicated for asymptomatic patients with positive serology alone 1, 2
• Suppressive therapy may be considered to reduce transmission risk to susceptible partners in discordant couples 3
• However, suppressive therapy is NOT effective to decrease transmission risk among persons with HIV/HSV-2 coinfection 3

Essential Patient Counseling (All HSV-2 Positive Patients)

Comprehensive education is required regardless of symptom status: 1, 2

Disease Education

• HSV-2 establishes lifelong latent infection that antivirals control but do not eradicate 1, 2
• Antivirals do not prevent all recurrences after discontinuation 1, 5
• Asymptomatic viral shedding occurs and can transmit infection even without visible lesions 2, 4

Transmission Prevention

• Abstain from sexual contact when prodromal symptoms or lesions are present 1, 2, 4
• Use condoms consistently during all sexual exposures (provides partial but not complete protection) 2
• Sex partners should be advised they might be infected even if asymptomatic 4
• Type-specific serologic testing of partners can determine if HSV-2 acquisition risk exists 3, 4
• Disclosure of HSV-2 status to partners is associated with reduced transmission risk 3

Special Populations

HIV-Infected Patients

• Routine type-specific serologic testing for HSV-2 should be considered in all persons seeking HIV care 3
• Higher antiviral doses required: Acyclovir 400 mg orally 3-5 times daily until clinical resolution 1
• For severe mucocutaneous lesions: IV acyclovir 5-10 mg/kg every 8 hours 3, 5
• Continue therapy until lesions completely heal 3
• Suppressive therapy does not reduce HIV transmission or HIV viral load in genital secretions 3
• Safety data for chronic suppressive therapy extends only to 6 months in HIV-infected patients 4

Pregnant Women

• Screening of pregnant women for HSV-2 is not recommended 3
• Safety of systemic acyclovir during pregnancy has not been fully established 1

Critical Pitfalls to Avoid

• Never treat based solely on positive serology without clinical symptoms 1, 2
• Never delay treatment beyond 72 hours of symptom onset for first episodes 1, 2
• Never delay treatment beyond 24 hours of symptom onset for recurrent episodes 4
• Never use topical acyclovir—it is substantially less effective than oral therapy 1, 2
• Never stop antiviral therapy prematurely in severe cases based on single negative test results 2, 5
• Do not use short-course therapy (1-3 days) in HIV-infected patients 3

Monitoring for Adverse Events

• Acyclovir, valacyclovir, and famciclovir are occasionally associated with nausea or headache 3
• No laboratory monitoring needed for episodic or suppressive therapy unless substantial renal impairment exists 3
• For high-dose IV acyclovir: monitor renal function at initiation and once or twice weekly during treatment 3
• Thrombotic thrombocytopenic purpura/hemolytic uremic syndrome reported with high-dose valacyclovir (8 g/day) but not at standard HSV treatment doses 3

Treatment Failure

• Suspect acyclovir resistance if lesions do not begin to resolve within 7-10 days after initiation of therapy 3
• Case reports suggest brincidofovir, imiquimod, and topical cidofovir may be useful for acyclovir-resistant infections 3