Treatment of Herpes Infections
For herpes labialis (cold sores), initiate valacyclovir 2 grams twice daily for 1 day (12 hours apart) at the earliest symptom, which reduces episode duration by approximately 1 day compared to placebo. 1
Herpes Labialis (Cold Sores)
First-Line Episodic Treatment
- Valacyclovir 2 grams twice daily for 1 day is the preferred regimen, taken 12 hours apart at the first sign of prodrome (tingling, itching, or burning) 1
- Alternative: Famciclovir 1500 mg as a single dose, which significantly reduces healing time of primary lesions 2, 3
- Alternative: Acyclovir 400 mg five times daily for 5 days (less convenient dosing) 2
Critical timing consideration: Treatment must be initiated within 24 hours of symptom onset—preferably during the prodrome—as peak viral titers occur in the first 24 hours and efficacy decreases dramatically after lesions fully develop 2, 3
Suppressive Therapy for Frequent Recurrences
For patients with ≥6 recurrences per year: 2, 3
- Valacyclovir 500 mg once daily (increase to 1000 mg once daily for ≥10 episodes/year) 2, 3
- Alternative: Famciclovir 250 mg twice daily 2, 3
- Alternative: Acyclovir 400 mg twice daily 2, 3
Suppressive therapy reduces recurrence frequency by ≥75% and has documented safety for acyclovir up to 6 years, and valacyclovir/famciclovir for 1 year 2, 3. After 1 year of continuous therapy, discontinue to reassess recurrence rate, as frequency naturally decreases over time 2, 3
Genital Herpes
First Clinical Episode
- Acyclovir 400 mg orally three times daily for 7-10 days, OR 2
- Valacyclovir 1 gram twice daily for 10 days, OR 2
- Famciclovir 250 mg three times daily for 7-10 days 2
Extend treatment beyond 10 days if healing is incomplete 2. Most effective when initiated within 48 hours of symptom onset 2, 1
Recurrent Episodes (Episodic Treatment)
- Valacyclovir 500 mg twice daily for 3 days (shortest effective regimen), OR 2, 1
- Acyclovir 800 mg twice daily for 5 days, OR 2
- Famciclovir 125 mg twice daily for 5 days 2
Initiate at first sign of prodrome or lesions 2. A 2-day course of acyclovir 800 mg three times daily has also shown efficacy in reducing lesion duration from 6 to 4 days 4
Suppressive Therapy
For patients with frequent recurrences (≥6 per year): 2, 1
- Valacyclovir 1000 mg once daily (or 500 mg once daily for ≤9 recurrences/year), OR 2, 1
- Famciclovir 250 mg twice daily, OR 2
- Acyclovir 400 mg twice daily 2
For HIV-infected patients with CD4+ ≥100 cells/mm³: Valacyclovir 500 mg twice daily 1
Important caveat: Suppressive therapy reduces but does not eliminate asymptomatic viral shedding, so transmission risk persists 2, 3
Herpes Simplex Encephalitis
Acyclovir 10 mg/kg IV every 8 hours for 14-21 days in adults and children with normal renal function 2. For neonates, use 20 mg/kg IV every 8 hours for 21 days, which has reduced mortality to 5% 2
Initiate empirically in all suspected encephalitis cases immediately, pending diagnostic confirmation 2. Predictors of poor outcome include age >30 years, Glasgow coma score <6, and delay >4 days before starting therapy 2
Common Pitfalls to Avoid
- Never rely on topical antivirals alone—they provide minimal benefit compared to oral therapy and are ineffective for suppression as they cannot reach viral reactivation sites 2, 3
- Do not delay treatment—waiting until lesions are fully developed significantly reduces efficacy; patients should have medication on hand to self-initiate at prodrome 2, 3
- Avoid underdosing—short-course, high-dose regimens (e.g., valacyclovir 2g twice daily for 1 day) are more effective and improve adherence compared to traditional 5-day courses 3, 1
- Do not overlook suppressive therapy in patients with ≥6 recurrences per year who experience significant quality of life impact 2, 3
Resistance Considerations
Acyclovir resistance remains rare (<0.5%) in immunocompetent patients, even with long-term suppressive therapy 2, 3. In immunocompromised patients with suspected resistance, consider foscarnet 40 mg/kg IV three times daily 3