What is the recommended daily oral antiviral regimen for chronic suppressive therapy of recurrent herpes simplex virus infection, including dosing and adjustments for pregnancy, immunocompromise, or renal impairment?

HSV Suppression: Recommended Daily Antiviral Regimens

For chronic suppressive therapy of recurrent HSV infection in immunocompetent adults, prescribe valacyclovir 500 mg once daily (or 1 gram once daily for patients with ≥10 recurrences per year), acyclovir 400 mg twice daily, or famciclovir 250 mg twice daily. 1

Standard Suppressive Regimens for Immunocompetent Adults

The CDC-recommended options for daily suppressive therapy include: 1

• Valacyclovir 500 mg once daily (preferred for convenience and adherence) 2
• Valacyclovir 1,000 mg once daily (for patients with ≥10 recurrences per year, as 500 mg once daily is less effective in this population) 1
• Acyclovir 400 mg twice daily (longest safety data, documented efficacy up to 6 years) 1, 3
• Famciclovir 250 mg twice daily 1

Valacyclovir and famciclovir offer superior convenience with less frequent dosing compared to acyclovir, which may improve long-term adherence for chronic therapy. 1, 3

Clinical Efficacy and Expected Outcomes

• Daily suppressive therapy reduces genital herpes recurrence frequency by ≥75% in patients with frequent recurrences (defined as ≥6 episodes per year) 1, 3
• Safety and efficacy have been documented for acyclovir for up to 6 years of continuous use 1, 3
• Valacyclovir and famciclovir have documented 1-year safety data, though clinical experience now extends beyond this timeframe 1, 4, 5, 6
• Suppressive therapy has not been associated with emergence of clinically significant acyclovir resistance in immunocompetent patients 1, 3

Special Population Adjustments

HIV-Infected Patients (Immunocompromised)

• For HIV-infected patients with CD4+ count ≥100 cells/mm³, use valacyclovir 500 mg twice daily (higher dose than immunocompetent patients) 2
• This population requires more aggressive suppression due to increased viral shedding and recurrence rates 2

Pregnancy

• While the provided evidence does not contain specific pregnancy dosing guidelines, suppressive therapy near term is commonly used to prevent neonatal transmission 7
• Acyclovir has the longest safety track record in pregnancy among the antivirals 7

Renal Impairment

• Dose adjustments are mandatory for all antivirals in renal impairment to prevent acute renal failure 8
• Valacyclovir and famciclovir require more aggressive dose reduction than acyclovir due to higher drug concentrations 8
• Monitor renal function at baseline and periodically during therapy 8

Duration and Reassessment Strategy

After 1 year of continuous suppressive therapy, discontinue treatment temporarily to reassess the patient's recurrence rate, as the frequency of recurrences decreases over time in many patients. 1, 3

This reassessment serves two purposes: 1, 3

• Evaluates the patient's psychological adjustment to genital herpes
• Determines if continued suppression is necessary based on current recurrence frequency

Critical Counseling Points and Caveats

Transmission Risk Remains

Suppressive acyclovir reduces but does not eliminate asymptomatic viral shedding, so transmission risk persists even on therapy. 1, 3

• Patients must understand that suppressive therapy decreases but does not eliminate the risk of transmitting HSV to sexual partners 1, 3
• Valacyclovir 500 mg once daily is specifically FDA-approved for reduction of transmission in source partners with ≤9 recurrences per year 2

Does Not Eradicate Latent Virus

• Antiviral therapy does not eradicate latent HSV from nerve ganglia 3
• After discontinuation, recurrence risk returns to baseline over time 3

Alternative Dosing for Dose Titration

• An alternative acyclovir regimen of 200 mg orally 3-5 times daily allows titration to the lowest effective dose 3, 7
• This approach may be useful for patients seeking to minimize medication exposure while maintaining suppression 3

Common Pitfalls to Avoid

• Do not use valacyclovir 500 mg once daily in patients with ≥10 recurrences per year—this dose is less effective in this high-frequency population; use 1,000 mg once daily instead 1
• Do not use topical acyclovir as primary therapy—it provides no improvement in systemic symptoms and is significantly less effective than oral formulations 7
• Do not forget to counsel about persistent transmission risk—patients often mistakenly believe suppressive therapy eliminates all transmission risk 1, 3
• Do not continue indefinitely without reassessment—recurrence frequency naturally decreases over time in many patients, making continued suppression potentially unnecessary 1, 3