Acyclovir Effectiveness for Preventing Herpes Recurrence
Daily suppressive acyclovir therapy at 400 mg twice daily reduces recurrence frequency by at least 75% in patients with frequent genital herpes outbreaks (≥6 episodes per year), and this regimen is highly effective and safe for continuous use up to 6 years. 1, 2
Indications for Suppressive Therapy
- Suppressive therapy is most appropriate for patients experiencing ≥6 recurrences per year 1, 2
- While acute episodes can be treated successfully with episodic therapy (200 mg 5 times daily or 400 mg 3 times daily for 5 days), chronic suppression is reserved for those with frequent or severe recurrences 3, 1
- The decision to initiate suppressive therapy should be based on recurrence frequency and impact on quality of life 3
Standard Suppressive Dosing Regimen
- The primary recommended dose is acyclovir 400 mg orally twice daily 1, 2
- An alternative regimen of 200 mg orally 3-5 times daily can be used to identify the lowest effective dose for individual symptom control 2
- This dosing differs substantially from episodic treatment and should not be confused with acute outbreak management 1
Efficacy Data
Long-term suppression demonstrates remarkable effectiveness:
- Greater than 95% of patients experience prevention or reduction in frequency/severity of recurrences during suppressive therapy 4
- In patients receiving 400 mg twice daily for 3 years, 45%, 52%, and 63% remained completely recurrence-free in years 1,2, and 3 respectively 4
- Serial quarterly analyses showed 71-87% of patients remained recurrence-free in each 3-month period 4
- Mean annual recurrence rates declined from 12.9 episodes pre-treatment to 1.7 during the first year and 0.8 by the fifth year 5
- More than 20% of patients receiving continuous 5-year suppressive therapy remained completely recurrence-free throughout the entire period 5
Duration and Re-evaluation Strategy
- Safety and efficacy are well-established for continuous daily therapy up to 6 years 2, 5
- After 1 year of continuous suppressive therapy, discontinuation should be discussed to reassess the patient's natural recurrence rate 2
- Pre-treatment recurrence frequencies typically return after discontinuation, as acyclovir does not eradicate latent virus 3, 6, 7
Critical Limitations and Caveats
Important considerations that affect clinical decision-making:
- Suppressive acyclovir reduces but does not eliminate asymptomatic viral shedding, so the extent to which it prevents HSV transmission to partners remains unknown 2
- The drug does not eradicate viral latency, and recurrences return to baseline frequency after discontinuation 3, 6, 7
- Some patients may develop prodromal symptoms or erythema even while effectively suppressed 8
- Suppressive therapy has not been associated with emergence of clinically significant acyclovir resistance among immunocompetent patients, even after 6 years of continuous use 2, 5
Non-Genital Herpes Simplex
- For recurrent non-genital HSV infection (such as orolabial herpes) with ≥8 episodes per year, acyclovir 200 mg 4 times daily effectively suppresses lesion development in the majority of patients 8
- However, prodromal symptoms and occasional erythema may still occur despite suppression 8
Comparison with Alternative Antivirals
- Valacyclovir and famciclovir offer superior bioavailability and less frequent dosing compared to acyclovir 1
- Valacyclovir 500 mg once daily is effective for patients with <10 recurrences per year, while 1 g once daily or 250 mg twice daily is more effective for those with ≥10 recurrences annually 9
- These alternatives may improve adherence due to simplified dosing schedules 1