How should I manage a patient with genital HSV‑2 lesions that are spreading despite a 7‑day course of oral acyclovir 400 mg twice daily?

Management of HSV-2 Spreading Despite Acyclovir Treatment

Your patient is receiving an inadequate dose of acyclovir—400 mg twice daily is the suppressive dose for preventing recurrences, not the treatment dose for active genital herpes, which requires either 400 mg three times daily or 800 mg twice daily for 5-7 days. 1

Immediate Action: Correct the Dosing Error

The CDC explicitly recommends for recurrent genital HSV episodes: 1

• Acyclovir 400 mg orally 3 times daily for 5 days, OR
• Acyclovir 800 mg orally 2 times daily for 5 days 1

Your current regimen of 400 mg twice daily is the suppressive therapy dose used for patients with ≥6 episodes per year to prevent recurrences, not to treat active disease. 1, 2 This underdosing explains why lesions continue to spread.

Escalation Algorithm if Corrected Dosing Fails

Step 1: Increase to Proper Treatment Dose

• Switch immediately to acyclovir 800 mg orally 5 times daily for 7-10 days 3
• Continue until complete clinical resolution, not just an arbitrary 7-day endpoint 1

Step 2: Consider IV Therapy for Severe Disease

Escalate to intravenous acyclovir 5-10 mg/kg every 8 hours if: 1, 2

• Severe disease requiring hospitalization
• Extensive mucocutaneous involvement
• Inability to tolerate oral medication
• Immunocompromised status (HIV, transplant, chemotherapy)
• Disseminated infection or CNS involvement

The CDC specifies that once lesions begin to regress on IV therapy, transition to oral acyclovir 400 mg three times daily until complete healing. 1

Step 3: Suspect Acyclovir Resistance

If lesions persist or worsen after 5-7 days of proper-dose oral therapy (800 mg 5x/day), consider resistance: 1, 3

• Obtain viral culture with susceptibility testing 3
• Acyclovir resistance is rare in immunocompetent patients but occurs in immunocompromised hosts with prolonged exposure 3
• For confirmed resistance: Foscarnet 40 mg/kg IV three times daily OR 60 mg/kg IV twice daily 1, 3

Critical Clinical Pitfalls

Common dosing error: The 400 mg twice daily regimen reduces recurrence frequency by ≥75% in suppressive therapy but is insufficient for treating active outbreaks. 1, 2 This is the most likely explanation for your patient's treatment failure.

Duration matters: For first-episode genital herpes, treatment should continue for 7-10 days until clinical resolution, not a fixed 5-day course. 2 Recurrent episodes typically require 5 days, but extend if lesions remain active. 1

Immunocompromised patients require higher doses: If your patient has HIV, is on immunosuppressive therapy, or has other immune compromise, they need acyclovir 400 mg orally 3-5 times daily for longer duration (14 days or until complete resolution). 1

Monitoring and Follow-Up

• Ensure adequate hydration, as acyclovir is renally excreted and requires dose adjustment in renal insufficiency 1
• If switching to IV therapy, monitor renal function at initiation and weekly during treatment 4
• Viral shedding and transmission can occur during asymptomatic periods despite therapy 2

The bottom line: Your patient needs immediate dose escalation to 800 mg five times daily or 400 mg three times daily—the current 400 mg twice daily regimen is categorically insufficient for treating active HSV-2 lesions. 1, 2