What are the recommended treatment regimens for genital herpes (herpes simplex virus type 2) in adults, including primary infection, recurrent episodes, suppressive therapy, and special considerations for immunocompromised patients and pregnant women?

Treatment of Genital Herpes

For genital herpes, use oral antiviral therapy with valacyclovir or acyclovir as first-line treatment, with specific regimens depending on whether the presentation is a first clinical episode, recurrent outbreak, or requires suppressive therapy. 1

First Clinical Episode

For initial genital herpes infection, treat with acyclovir 200 mg orally 5 times daily for 7-10 days or until clinical resolution. 2 This represents the established standard for primary infection, though newer agents offer more convenient dosing.

Alternative regimens for first episodes include:

• Valacyclovir 500 mg orally twice daily for 5 days 1
• Acyclovir 400 mg orally 5 times daily for first episode herpes proctitis, extended to 10 days 2

The CDC emphasizes that systemic acyclovir provides partial control of symptoms and signs during first clinical episodes, though it neither eradicates latent virus nor affects subsequent recurrence risk after discontinuation. 2 Topical acyclovir is substantially less effective than oral therapy and should not be used. 2, 1

Recurrent Episodes

For recurrent genital herpes, episodic treatment is most effective when initiated during prodrome or within 1 day of lesion onset. 1 The CDC recommends several equivalent options:

• Valacyclovir 500 mg orally twice daily for 5 days (preferred for convenience) 1
• Acyclovir 800 mg orally twice daily for 5 days 2, 1
• Acyclovir 400 mg orally three times daily for 5 days 2, 1
• Acyclovir 200 mg orally five times daily for 5 days 2, 1
• Famciclovir 125 mg orally twice daily for 5 days 1

Valacyclovir offers superior bioavailability compared to acyclovir, requiring less frequent dosing and potentially improving adherence. 3 It is the only antiviral FDA-approved for a 3-day episodic treatment regimen, though the 5-day course remains standard in CDC guidelines. 3

A critical caveat: most immunocompetent patients with recurrent disease do not benefit substantially from episodic treatment unless initiated very early, so this approach is not universally recommended for all recurrences. 2

Daily Suppressive Therapy

For patients with frequent recurrences (≥6 episodes per year), daily suppressive therapy reduces recurrence frequency by at least 75%. 2, 1

Recommended suppressive regimens:

• Valacyclovir 1 g orally once daily (preferred for once-daily dosing) 1
• Valacyclovir 500 mg orally once daily (alternative lower dose) 1
• Acyclovir 400 mg orally twice daily 2, 1
• Famciclovir 250 mg orally twice daily 1

A meta-analysis confirmed that acyclovir 400 mg twice daily, valacyclovir 250 mg twice daily, famciclovir 250 mg twice daily, and valacyclovir 500 mg once daily all demonstrate similar efficacy. 4 Valacyclovir once-daily dosing is unique and may enhance adherence. 3

After 1 year of continuous suppressive therapy, discontinue treatment temporarily to reassess the patient's recurrence rate. 2, 1 Safety and efficacy have been documented for continuous use up to 5-6 years with acyclovir and 1 year with valacyclovir. 1, 5 Long-term data show that 20% of patients on 5-year suppressive therapy remain completely recurrence-free. 5

Important limitation: Suppressive therapy does not eliminate asymptomatic viral shedding or completely prevent transmission. 2, 1

Severe Disease Requiring Hospitalization

For severe genital herpes with complications (disseminated infection, encephalitis, pneumonitis, hepatitis), use intravenous acyclovir 5-10 mg/kg every 8 hours for 5-7 days or until clinical resolution. 2

Immunocompromised Patients

HIV-infected and other immunocompromised patients may have prolonged episodes with extensive disease requiring more aggressive therapy. 2 These patients may experience more frequent and severe episodes. 4

For immunocompromised hosts:

• Consider higher oral doses or longer treatment duration 2
• Valacyclovir 500 mg twice daily maintains clinical efficacy and safety comparable to acyclovir in this population 4
• Monitor for acyclovir-resistant strains, which have been isolated from patients receiving suppressive therapy 2

If lesions do not begin resolving within 7-10 days of therapy, suspect acyclovir resistance. 1 For proven or suspected acyclovir resistance, use foscarnet 40 mg/kg IV every 8 hours as an alternative. 1 All acyclovir-resistant strains are also resistant to valacyclovir, and most resist famciclovir. 1

Pregnancy Considerations

The CDC states that routine suppressive therapy is not recommended during pregnancy for recurrent genital herpes, as the safety of systemic acyclovir and valacyclovir in pregnancy has not been definitively established. 1 However, this remains an evolving area with ongoing studies. 6

Patient Counseling Essentials

Patients must understand:

• Genital herpes is a recurrent, incurable viral disease; antivirals control symptoms but do not eradicate the virus 1
• Abstain from sexual activity when lesions or prodromal symptoms are present 2, 1
• Asymptomatic viral shedding can occur, potentially leading to transmission even without visible lesions 2, 1
• Use condoms during all sexual exposures with new or uninfected partners 1
• Inform sex partners about having genital herpes 1

Common Pitfalls to Avoid

• Never use topical acyclovir—it is substantially less effective than oral therapy 2, 1
• Do not use valacyclovir 8 g/day in immunocompromised patients due to risk of hemolytic uremic syndrome/thrombotic thrombocytopenic purpura 1
• Do not assume episodic treatment benefits all patients with recurrent disease—early initiation is critical for efficacy 2, 1
• Do not continue suppressive therapy indefinitely without periodic reassessment 2, 1