Can oral acyclovir be used to treat herpes simplex cold sores?

Oral Acyclovir for Herpes Simplex Cold Sores

Yes, oral acyclovir is effective for treating herpes simplex cold sores (orolabial herpes), with the CDC recommending 200 mg five times daily for 7-10 days, or alternatively 400 mg five times daily for 5-10 days for active lesions. 1

Treatment Approach for Active Cold Sores

For episodic treatment of orolabial HSV lesions:

• Standard dosing: Acyclovir 200 mg orally 5 times daily for 7-10 days until complete healing 1
• Alternative regimen: Acyclovir 400 mg orally 5 times daily for 5-10 days 2
• Early initiation is critical - treatment should begin at the first sign or symptom (prodrome stage) for maximum benefit 1, 3

The evidence strongly supports that starting treatment within 1 hour of first symptoms significantly improves outcomes, reducing pain duration by 36% and healing time by 27% when initiated during prodrome or erythema stage 3. Treatment initiated during the prodrome or within 2 days of lesion onset provides the most benefit 2.

Efficacy and Clinical Outcomes

Oral acyclovir demonstrates clear therapeutic benefit for cold sores:

• Reduces viral shedding - significantly fewer positive viral cultures (25% vs 48% with placebo) 3
• Accelerates healing - shortens time to complete resolution when started early 4, 5
• Decreases pain duration - particularly when treatment begins in prodromal phase 3
• Does not prevent lesion development in all cases, but hastens resolution among those who start treatment early 3

Suppressive Therapy for Frequent Recurrences

For patients with frequent or severe recurrences of orolabial herpes:

• Daily suppressive therapy is recommended: Acyclovir 400 mg orally twice daily 2, 1
• Alternative suppressive regimen: Acyclovir 200 mg orally 3-5 times daily 2
• Reduces recurrence frequency by at least 75% in patients with frequent episodes 2, 1
• After 1 year of continuous therapy, discontinue to reassess recurrence rate 2

The CDC emphasizes that suppressive therapy is appropriate for those with frequent or severe recurrences, though it does not eliminate asymptomatic viral shedding or completely prevent transmission 2.

Special Populations

Immunocompromised patients require modified dosing:

• Higher doses recommended: Acyclovir 400 mg orally 3-5 times daily until clinical resolution 1
• More aggressive therapy may be needed for HIV-infected patients 2, 1
• Severe disease requiring hospitalization: IV acyclovir 5-10 mg/kg every 8 hours 2

For acyclovir-resistant HSV (more common in immunocompromised patients):

• IV foscarnet is the treatment of choice 2, 1
• Topical alternatives include trifluridine, cidofovir, or imiquimod for external lesions 2

Important Clinical Caveats

Key limitations to understand:

• Acyclovir does not eradicate latent virus - the virus remains dormant in nerve ganglia and can reactivate 4, 5
• Topical acyclovir is substantially less effective than oral formulations and is discouraged 2
• Treatment does not affect future recurrence risk after discontinuation 4
• Resistance can develop, particularly with long-term suppressive use in immunocompromised patients, though this is uncommon in immunocompetent individuals 2

Monitoring for treatment failure:

• Suspect resistance if lesions do not begin resolving within 7-10 days of therapy initiation 2
• Obtain viral culture and susceptibility testing if resistance suspected 2

Prevention Counseling

Patients should be advised:

• Avoid sexual/close contact when lesions are present 2, 1
• Use latex condoms consistently to reduce transmission risk 2, 1
• Transmission can occur during asymptomatic periods despite absence of visible lesions 2