Treatment of Acute Genital Herpes Outbreak
For an otherwise healthy adult experiencing their first episode of genital herpes, start oral valacyclovir 1 g twice daily for 7–10 days, which offers superior convenience and equivalent efficacy to acyclovir. 1
First-Line Treatment Options for Initial Episode
The CDC endorses multiple oral antiviral regimens for first-episode genital herpes, all with comparable efficacy: 1
- Valacyclovir 1 g orally twice daily for 7–10 days – preferred for convenient dosing 1
- Acyclovir 400 mg orally three times daily for 7–10 days 1
- Acyclovir 200 mg orally five times daily for 7–10 days 2, 1
- Famciclovir 250 mg orally three times daily for 7–10 days 1
Extend therapy beyond 10 days if lesions have not completely healed. 1 Large ulcers may require ≥2 weeks for full clinical resolution. 2
Why Oral Therapy Is Essential
Topical acyclovir is substantially less effective than systemic oral antivirals and should never be used as monotherapy because it fails to reduce systemic symptoms, viremia, or viral shedding from the cervix, urethra, or pharynx. 1, 3 The FDA label confirms topical formulations are far inferior to oral administration. 4
Severe Disease Requiring Hospitalization
For patients with disseminated HSV infection, encephalitis, pneumonitis, hepatitis, or inability to tolerate oral medication, administer intravenous acyclovir 5–10 mg/kg every 8 hours for 5–7 days or until clinical resolution. 1, 3 Indications for IV therapy include: 1
- Central nervous system involvement
- Visceral organ involvement
- Extensive mucocutaneous disease preventing oral intake
- Immunocompromised status with severe presentation
Special Consideration: Herpes Proctitis
For first-episode herpes proctitis, use acyclovir 400 mg orally five times daily for 10 days (not the standard 7–10 day course), reflecting the need for higher dosing at the rectal site. 2, 1
Treatment of Recurrent Episodes
Provide all patients with a prescription for episodic therapy to self-initiate at the very first sign of prodrome or within 24 hours of lesion onset, when viral replication peaks and treatment is most effective. 1 Delaying beyond 72 hours substantially reduces benefit. 5
Episodic Treatment Regimens (5-Day Course)
The CDC recommends any of these equivalent options: 1
- Valacyclovir 500 mg orally twice daily for 5 days 1
- Acyclovir 800 mg orally twice daily for 5 days 1
- Acyclovir 400 mg orally three times daily for 5 days 1
- Famciclovir 125 mg orally twice daily for 5 days 1
Valacyclovir and famciclovir offer more convenient dosing schedules with comparable clinical outcomes to acyclovir. 5, 6 Research demonstrates that single-day high-dose famciclovir (1000 mg twice daily) can abort lesions and reduce healing time by approximately 2 days, though this is not yet a standard CDC recommendation. 7
Daily Suppressive Therapy
Offer daily suppressive therapy to patients experiencing ≥6 recurrences per year, which reduces recurrence frequency by ≥75%. 1, 3 This is a firm threshold supported by multiple CDC guidelines. 8
Suppressive Dosing Options
- Valacyclovir 1 g orally once daily (standard dose) 1
- Valacyclovir 500 mg orally once daily (for patients with <10 recurrences/year) 1
- Acyclovir 400 mg orally twice daily (safety documented up to 6 years) 1
- Famciclovir 250 mg orally twice daily (safety documented up to 1 year) 1
Critical Pitfall to Avoid
Do not use valacyclovir 500 mg once daily in patients with ≥10 recurrences per year; it is less effective than higher-dose regimens in this population. 1 Use the 1 g daily dose instead.
Reassessment Strategy
After 1 year of continuous suppressive therapy, discontinue temporarily to reassess recurrence frequency, as the natural history often shows declining episode frequency over time. 1, 5
Essential Patient Counseling
Patients must understand these key facts to prevent transmission and manage expectations: 1
- Genital herpes is a chronic, incurable infection with potential for lifelong recurrences. 1
- Asymptomatic viral shedding occurs even without visible lesions and can transmit infection to partners, even while on suppressive therapy. 1
- Abstain from all sexual activity during active lesions or prodromal symptoms. 1
- Use condoms during all sexual encounters with new or uninfected partners, though condoms do not completely eliminate transmission risk. 1
- Inform all sexual partners about the HSV infection. 1
- Antiviral medications control symptoms but do not eradicate the virus or prevent all recurrences. 1
Neonatal Transmission Risk
Women of childbearing age must understand that neonatal transmission risk is 25–44% with a primary episode at delivery versus ≈1% with recurrent infection. 1 Pregnant women with genital herpes should inform their obstetric providers. 1
Special Populations
HIV-Infected Patients
For suppressive therapy in HIV-infected patients, use valacyclovir 500 mg orally twice daily (not once daily), as higher dosing is required for adequate viral control. 1 Daily suppressive therapy reduces HIV RNA concentrations in plasma and genital secretions. 1
Immunocompromised Patients
Higher doses of acyclovir (400 mg orally three to five times daily until clinical resolution) are required for immunocompromised patients. 1 If lesions persist despite acyclovir treatment, suspect viral resistance and consider IV foscarnet 40 mg/kg every 8 hours. 1
Antiviral Resistance
Suspect acyclovir resistance if lesions fail to improve within 7–10 days of appropriate therapy. 1 Confirm with viral culture and susceptibility testing. 1 Resistance is uncommon in immunocompetent hosts but more frequent in immunocompromised patients, especially those with HIV on long-term suppressive therapy. 1
Renal Function Monitoring
Assess renal function before starting and during antiviral therapy; adjust dosing frequency or total daily dose according to creatinine clearance to avoid toxicity. 1, 4 The FDA label emphasizes that dosage adjustment is mandatory in patients with renal impairment. 4 Maintain adequate hydration throughout treatment. 4