What is the recommended treatment for a patient with Herpes Simplex Virus type 2 (HSV-2) infection, considering factors such as symptom onset, renal function, and pregnancy status?

Treatment of HSV-2

For first-episode HSV-2 infection, initiate valacyclovir 1 g orally twice daily for 7-10 days, or acyclovir 400 mg orally three times daily for 7-10 days, or famciclovir 250 mg orally three times daily for 7-10 days. 1

First-Episode Treatment

Oral antiviral therapy is the cornerstone of first-episode HSV-2 management, with three equally effective options available 2, 1:

• Valacyclovir 1 g orally twice daily for 7-10 days (preferred for convenience) 2, 1
• Acyclovir 400 mg orally three times daily for 7-10 days OR 200 mg five times daily for 7-10 days 2, 1
• Famciclovir 250 mg orally three times daily for 7-10 days 2, 1

Extend treatment beyond 10 days if healing is incomplete at the end of the initial course 2, 1. For severe mucocutaneous disease requiring hospitalization, initiate IV acyclovir until lesions begin to regress, then transition to oral therapy 1.

Recurrent Episodes Treatment

For recurrent outbreaks, initiate episodic therapy at the first sign of prodrome or within 24 hours of lesion onset to maximize effectiveness 1, 3:

• Valacyclovir 500 mg orally twice daily for 3-5 days 1, 3
• Acyclovir 400 mg orally three times daily for 5 days 2, 1
• Famciclovir 125 mg orally twice daily for 5 days 1

Provide patients with a prescription to self-initiate treatment at the earliest symptom recognition 1. Treatment initiated after 24 hours of symptom onset has substantially reduced efficacy 3.

Short-Course Alternatives

A 2-day course of high-dose acyclovir (800 mg three times daily) significantly reduces lesion duration and viral shedding in immunocompetent patients 4. However, avoid short-course therapy (1-3 days) in HIV-infected patients 1.

Suppressive Therapy

Recommend daily suppressive therapy for patients with ≥6 recurrences per year, which reduces recurrence frequency by ≥75% 2, 1:

• Valacyclovir 500 mg once daily (for infrequent recurrences) 1, 3
• Valacyclovir 1000 mg once daily (for ≥10 episodes per year) 1, 3
• Acyclovir 400 mg twice daily 2, 1
• Famciclovir 250 mg twice daily 1

After 1 year of continuous suppressive therapy, reassess the need for continuation, as recurrence frequency naturally decreases over time in many patients 2. Suppressive therapy also reduces asymptomatic viral shedding, which may decrease transmission risk 1, 3.

HIV-Infected Patients

HIV-infected patients require higher doses and longer treatment duration 2, 1:

• For suppressive therapy: valacyclovir 500 mg twice daily (not once daily) 2, 1
• Avoid short-course regimens (1-3 days) in this population 1
• Monitor for treatment failure more closely, as acyclovir resistance is more common in immunocompromised hosts 2, 5

Pregnancy Considerations

Acyclovir is the first-choice antiviral for HSV-2 in pregnancy based on decades of safety data 2, 1:

• Offer episodic therapy for first-episode disease and recurrences during pregnancy 2, 1
• Consider suppressive therapy starting at 36 weeks gestation to reduce HSV shedding at delivery and decrease cesarean delivery need 1
• Cesarean delivery is mandatory for women with visible genital lesions or prodromal symptoms at labor onset, regardless of prior suppressive therapy 2, 1

Routine suppressive therapy is NOT recommended during pregnancy for women without frequent/severe recurrences or recent outbreaks 1.

Treatment Failure and Resistance

Suspect acyclovir resistance if lesions do not begin to resolve within 7-10 days of appropriately dosed therapy 2, 1:

• Obtain viral culture and susceptibility testing to confirm resistance 2, 1
• IV foscarnet 40 mg/kg every 8 hours is the treatment of choice for acyclovir-resistant HSV 2, 1, 5
• Topical alternatives include trifluridine, cidofovir gel, or imiquimod for external lesions, requiring 21-28 days of application 2, 5

Resistance is rare in immunocompetent patients but more common in HIV-infected individuals 2, 5.

Monitoring Requirements

No laboratory monitoring is needed for patients on episodic or suppressive therapy unless substantial renal impairment exists 2, 1. For patients receiving high-dose IV acyclovir, monitor renal function at treatment initiation and once or twice weekly during therapy, with dose adjustment as necessary 2.

Critical Patient Counseling

Comprehensive counseling is essential at diagnosis 2, 1, 3:

• HSV-2 is a chronic, incurable infection with potential for lifelong recurrence 2, 1
• Asymptomatic viral shedding occurs frequently, enabling transmission even without visible lesions 2, 3
• Abstain from sexual activity when lesions or prodromal symptoms are present 2, 1, 3
• Use condoms consistently with all partners, though this does not eliminate transmission risk 2, 3
• Inform sexual partners of HSV-2 status; uninfected partners should consider type-specific serologic testing 3
• Childbearing-aged women must inform obstetric providers about HSV-2 infection due to neonatal transmission risk 2, 1

Common Pitfalls to Avoid

• Never use topical acyclovir alone—it is substantially less effective than systemic therapy 1
• Do not delay treatment beyond 24 hours for recurrences or 72 hours for first episodes 1, 3
• Do not use once-daily valacyclovir for suppression in HIV-infected patients—twice-daily dosing is required 2, 1
• Do not assume suppressive therapy eliminates transmission risk—asymptomatic shedding still occurs, though at reduced frequency 2, 1