What is the recommended first‑line daily suppressive antiviral regimen for an adult with recurrent genital herpes (HSV‑2)?

Suppressive Management of Recurrent Genital Herpes (HSV-2)

For immunocompetent adults with recurrent genital HSV-2, valacyclovir 1000 mg once daily is the recommended first-line suppressive regimen, with 500 mg once daily reserved only for patients experiencing fewer than 10 recurrences per year. 1, 2, 3

Primary Dosing Algorithm

Step 1: Assess recurrence frequency

• Patients with ≥10 recurrences per year: Valacyclovir 1000 mg once daily 1, 2, 3
• Patients with <10 recurrences per year: Valacyclovir 500 mg once daily 1, 2, 3

The FDA label explicitly states that 500 mg once daily is less effective in patients with very frequent recurrences, making the 1000 mg dose critical for this population 2. This dose-response relationship was definitively established in a large randomized trial of 1479 patients 3.

Step 2: Alternative regimens if valacyclovir is not suitable

• Acyclovir 400 mg twice daily (documented safety for up to 6 years) 4, 1, 5
• Famciclovir 250 mg twice daily (documented safety for 1 year) 4, 1, 5

These alternatives provide comparable efficacy but require twice-daily dosing, which may reduce adherence 1, 3.

Special Population Modifications

HIV-infected patients with CD4+ ≥100 cells/mm³ require different dosing:

• Valacyclovir 500 mg TWICE daily (not once daily) 1, 2
• Once-daily regimens are inadequate for immunocompromised patients 1, 5

This is a critical pitfall—HIV-infected patients prescribed the standard once-daily dose will experience treatment failure 1, 5.

Clinical Benefits and Expectations

Suppressive therapy delivers measurable outcomes:

• Reduces recurrence frequency by ≥75% in patients with frequent outbreaks (≥6 per year) 4, 1, 5
• Decreases asymptomatic viral shedding (though does not eliminate it completely) 4, 1, 5
• Improves quality of life by preventing physical discomfort and psychological distress 5
• In HIV-infected patients, reduces HIV RNA concentrations in plasma and genital secretions 1

The full preventive effect builds gradually over the first few weeks of consistent therapy 6.

Duration and Reassessment Strategy

After 1 year of continuous suppressive therapy, discuss discontinuation with the patient to reassess recurrence frequency, as outbreak rates often decline over time 4, 1, 5, 6. This reassessment is important because many patients experience a natural decrease in recurrence frequency after several years of infection 4, 1.

Long-term safety is well-established: acyclovir has documented safety for up to 6 years, while valacyclovir and famciclovir have documented safety for 1 year 4, 1, 6.

Resistance and Treatment Failure

If lesions persist 7-10 days after initiating appropriate therapy, suspect antiviral resistance 1, 5. All acyclovir-resistant strains are also resistant to valacyclovir 1. For confirmed resistance, IV foscarnet 40 mg/kg every 8 hours until clinical resolution is the treatment of choice 1, 5.

Resistance rates remain remarkably low (<0.5%) in immunocompetent patients despite over 20 years of widespread use 1. In HIV-infected and other immunocompromised patients, resistance rates are higher (5-7%) but still relatively low 1.

Monitoring Requirements

No laboratory monitoring is needed unless the patient has substantial renal impairment 1, 5. For patients with CrCl 30-49 mL/min, no dose reduction is required 1.

Critical Counseling Points

Patients must understand that suppressive therapy:

• Does not eliminate asymptomatic viral shedding—transmission risk persists even on therapy 4, 1, 5, 6
• Does not eradicate the virus—recurrences may return after discontinuation 5
• Requires consistent daily adherence to maintain protective effect 6

Patients should be advised to abstain from sexual activity when lesions or prodromal symptoms are present and to use condoms during all sexual exposures with new or uninfected partners 4.

Common Pitfalls to Avoid

• Do not prescribe valacyclovir 500 mg once daily for patients with ≥10 recurrences per year—this dose is inadequate 1, 2, 3
• Do not prescribe valacyclovir 500 mg once daily for HIV-infected patients—they require 500 mg twice daily 1, 5, 2
• Do not use topical acyclovir as sole treatment—it is substantially less effective than systemic therapy 1
• Do not prescribe high-dose valacyclovir (8 g/day) in immunocompromised patients—this has been associated with thrombotic thrombocytopenic purpura/hemolytic uremic syndrome, though this has not been reported at standard suppressive doses 1, 5, 6