Guideline Summary for Maintenance Therapy of Genital Herpes

Immunocompetent Patients – Suppressive Regimens

Daily suppressive therapy with valacyclovir 500 mg once daily or acyclovir 400 mg twice daily reduces recurrence frequency by ≥75% in patients experiencing ≥6 recurrences per year. [CDC 1, 2]
Acyclovir 400 mg twice daily provides efficacy comparable to the valacyclovir regimen. [CDC 3, 4, 2]
Acyclovir 200 mg administered 3–5 times daily can be used to identify the lowest effective dose for suppressive therapy. [CDC 3, 4]
Famciclovir 250 mg twice daily achieves recurrence reduction comparable to acyclovir‑based regimens. [CDC 5]

Suppressive therapy lowers recurrence rates by >75% but does not eliminate asymptomatic viral shedding nor fully prevent transmission. [CDC 3, 4, 2]
After 12 months of continuous suppressive therapy, clinicians should consider discontinuation and reassess recurrence frequency, as episodes often decline over time. [CDC 3, 4, 2]
Long‑term safety is documented: acyclovir has been used safely for 5–6 years, while valacyclovir and famciclovir have demonstrated safety for at least 1 year of continuous use. [CDC 3, 5]

Valacyclovir 500 mg twice daily (not once daily) is the recommended dose for effective suppression in HIV‑infected individuals. [CDC 1, 6]
Acyclovir 400 mg taken 3–5 times daily serves as an alternative regimen for immunocompromised patients. [CDC 7, 8]
Famciclovir 500 mg twice daily effectively reduces recurrences and subclinical shedding in this population. [CDC 7, 8]

High‑dose valacyclovir (8 g/day) has been linked to thrombotic thrombocytopenic purpura/hemolytic uremic syndrome in immunocompromised patients; standard doses (≤1 g twice daily) are considered safe. [CDC 7, 1, 8, 6]
Daily suppressive therapy lowers HIV RNA concentrations in plasma and genital secretions, although the impact on HIV transmission remains uncertain. [CDC 1, 6]

Routine suppressive therapy is not recommended for pregnant women with recurrent genital herpes; however, administering acyclovir near term may reduce cesarean delivery rates by decreasing active lesions at delivery. [CDC 7, 8]
In pregnant patients with frequent, severe recurrences, acyclovir prophylaxis may be appropriate, with no reported pattern of adverse pregnancy outcomes after exposure. [American College of Physicians 9]

Suppressive therapy is advised only for patients with genital HSV‑1 who experience frequent recurrences, reflecting the generally lower recurrence rate of HSV‑1 compared with HSV‑2. [Clinical Infectious Diseases 10]

Suspect antiviral resistance when lesions persist or fail to begin resolving within 7–10 days of therapy initiation. [CDC 1, 6]
Acyclovir‑resistant HSV strains are typically cross‑resistant to valacyclovir and most are resistant to famciclovir. [CDC 7, 8]
First‑line treatment for proven or suspected acyclovir‑resistant HSV: foscarnet 40 mg/kg IV every 8 hours until clinical resolution. [CDC 7, 1, 8, 6]
Alternative for external lesions: topical cidofovir 1 % gel applied daily for five consecutive days. [CDC 7, 8]
Although resistant strains have been isolated from patients on suppressive therapy, they have not been associated with treatment failure in immunocompetent individuals. [CDC 3, 5]

No routine laboratory monitoring is required for patients on episodic or suppressive antiviral therapy unless they have significant renal impairment. [CDC 1, 6]
Common adverse events (headache, nausea, nasopharyngitis) occur infrequently and are comparable across all antiviral agents used for maintenance therapy. [CDC 1, 6]