What is the role of intralesional acyclovir (antiviral medication) in the treatment of plantar warts in immunocompetent patients?

Medical Advisory BoardAll articles are reviewed for accuracy by our Medical Advisory Board
Educational purpose only • Exercise caution as content is pending human review
Article Review Status
Submitted
Under Review
Approved

Last updated: January 8, 2026 • View editorial policy

Personalize

Help us tailor your experience

Which best describes you? Your choice helps us use language that's most understandable for you.

Intralesional Acyclovir for Plantar Warts

Intralesional acyclovir is not recommended for the treatment of plantar warts in immunocompetent patients, as it lacks guideline support and shows no superiority over placebo in the highest quality evidence available.

Evidence Against Intralesional Acyclovir

The British Association of Dermatologists 2014 guidelines do not include intralesional acyclovir as a recommended treatment option for plantar warts at any level of evidence 1. The guidelines mention only oral valaciclovir (a related antiviral) in the context of single case reports for immunosuppressed patients, not immunocompetent individuals 1.

Topical Acyclovir Evidence

The most rigorous evidence comes from a 1984 randomized controlled trial comparing topical acyclovir cream versus placebo cream versus liquid nitrogen in 52 patients with plantar warts 2. The study conclusively demonstrated that acyclovir cream (7 of 18 patients cleared) was no better than placebo cream (5 of 18 patients cleared) after 8 weeks of treatment 2. This represents the gold standard evidence for acyclovir in plantar warts and directly contradicts its use.

Recent Intralesional Studies Show Conflicting Results

Two recent studies examined intralesional acyclovir specifically:

  • A 2024 randomized controlled trial found 37.5% complete response with intralesional acyclovir versus 18.7% with saline control, but noted that 100% of patients receiving intralesional acyclovir experienced pain compared to 56.3% with Hepatitis-B vaccine 3.

  • A 2025 study reported 65% complete clearance with intralesional acyclovir versus 70% with Candida antigen, showing acyclovir was slightly inferior to established immunotherapy 4.

Critical caveat: These newer studies are small, lack guideline endorsement, and show acyclovir performing worse than or equal to established intralesional immunotherapies that themselves have only level 1 evidence with insufficient support for routine recommendation 1.

Recommended Treatment Alternatives

First-Line Treatment

  • Salicylic acid 15-26% applied daily after keratin removal with occlusion for 3-4 months (Strength of Recommendation A) 1, 5.

Second-Line Options for Resistant Cases

  • Contact immunotherapy with DPC or SADBE: 88% complete clearance in palmoplantar warts over median 5 months (Strength of Recommendation C) 1.
  • Cryotherapy: Applied every 2-4 weeks for at least 3 months, though cure rates are lower for plantar warts due to thick cornified layer 1, 5.
  • Intralesional Candida antigen: 47-87% clearance rates, superior to acyclovir in head-to-head comparison 1, 4.

Alternative Destructive Therapies

  • 5-Fluorouracil 5% cream under occlusion: 95% clearance in plantar warts after 12 weeks (Strength of Recommendation C) 1.
  • Bleomycin intralesional: 0.1-1 U/mL injected into wart after local anesthesia, 1-3 treatments (Strength of Recommendation B) 1.

Why Acyclovir Fails Mechanistically

Plantar warts are caused by human papillomavirus (HPV), not herpes simplex virus 3, 4. Acyclovir is a nucleoside analogue designed specifically for herpes viruses and has no established antiviral activity against HPV 2. Any observed benefit in recent small studies likely represents immunomodulatory effects from the injection trauma itself rather than specific antiviral action, explaining why it performs no better than other intralesional agents or even placebo 3, 4, 2.

Clinical Algorithm

For immunocompetent patients with plantar warts:

  1. Start with salicylic acid 15-26% daily with occlusion for 3-4 months 1, 5
  2. If no response after 3 months, switch to contact immunotherapy (DPC/SADBE) or intralesional Candida antigen 1
  3. For single resistant lesions, consider bleomycin intralesional injection or 5-FU under occlusion 1
  4. Do not use intralesional acyclovir as it lacks guideline support and shows no superiority over placebo 1, 2

Important safety note: The British Association of Dermatologists recommends changing treatment modality if there is no substantial improvement after 3 provider-administered treatments 6. Do not persist with ineffective therapies beyond recommended timeframes 5.

References

1
Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

5
Guideline

Plantar Wart Treatment Guidelines

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2026

6
Guideline

Cantharidin Treatment for Cutaneous Warts

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Related Questions

Can you participate in sports after liquid nitrogen treatment for plantar warts?
Is the MMR (Measles, Mumps, Rubella) vaccine effective for treating plantar warts?
What is the recommended treatment approach for a patient with hypertension in an outpatient setting, considering comorbidities such as diabetes and kidney disease?
What is the best course of action for a male adult patient with a history of Diabetes Mellitus (DM) and nephrolithiasis, presenting with left-sided back pain and hematuria?
What does a 2D echo showing a normal left ventricle with segmental wall motion abnormalities, adequate systolic function, Doppler evidence of impaired diastolic relaxation, and aortic and mitral sclerosis mean, and how should it be managed?
What is the initial approach to managing erectile dysfunction in a male patient in an outpatient internal medicine setting?
What is the recommended dose of Levosalbutamol (Levalbuterol) for a patient with a history of asthma or chronic obstructive pulmonary disease (COPD) experiencing an acute asthma attack?
What is the dosage and use of lactulose for an adult or geriatric patient with constipation or hepatic encephalopathy?

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

Have a follow-up question?

Our Medical A.I. is used by practicing medical doctors at top research institutions around the world. Ask any follow up question and get world-class guideline-backed answers instantly.

Ask Question