What are the topical treatment options for Herpes Simplex Virus 2 (HSV 2)?

Topical Treatment for HSV-2

Topical antiviral therapy for genital HSV-2 is substantially less effective than oral systemic therapy and is strongly discouraged for treatment of genital herpes. 1, 2

Why Topical Therapy Is Not Recommended for Genital HSV-2

• The CDC explicitly states that topical acyclovir is substantially less effective than oral systemic drugs and its use is discouraged for genital herpes. 1, 2
• Systemic oral antivirals (acyclovir, valacyclovir, famciclovir) provide superior clinical benefit by controlling symptoms and signs of herpes episodes, while topical therapy fails to achieve adequate therapeutic levels. 1
• The evidence base consistently demonstrates that oral therapy is the standard of care, with topical formulations showing minimal to no therapeutic benefit for genital lesions. 1

Recommended Oral Treatment Instead

For First Clinical Episode of Genital HSV-2:

• Acyclovir 400 mg orally three times daily for 7-10 days 1
• Alternative: Valacyclovir 1 g orally twice daily for 7-10 days 1
• Alternative: Famciclovir 250 mg orally three times daily for 7-10 days 1, 3

For Recurrent Episodes:

• Valacyclovir 500 mg orally twice daily for 5 days (preferred episodic therapy) 2
• Alternative: Acyclovir 800 mg orally twice daily for 5 days 2
• Alternative: Famciclovir 125 mg orally twice daily for 5 days 2, 3
• Treatment is most effective when started during prodrome or within 1 day of lesion onset. 2

For Suppressive Therapy (≥6 recurrences/year):

• Valacyclovir 1 g orally once daily 2
• Alternative: Acyclovir 400 mg orally twice daily 2
• Alternative: Famciclovir 250 mg orally twice daily 2, 3

Limited Role for Topical Antivirals

When Topical Therapy May Be Considered:

• Topical antivirals are only appropriate for HSV epithelial keratitis (eye infections), not genital herpes. 4
• For ocular HSV: Ganciclovir 0.15% gel 3-5 times daily is preferred first-line topical agent, combined with oral antivirals. 4
• For acyclovir-resistant mucocutaneous HSV in immunocompromised patients: Trifluorothymidine ophthalmic solution applied 3-4 times daily to accessible lesions may be attempted. 5

Research Context (Not Standard Practice):

• Penciclovir cream has shown some efficacy in research settings for herpes labialis (cold sores), reducing lesion duration and pain compared to acyclovir cream. 6, 7
• However, this evidence applies to orolabial herpes (HSV-1), not genital HSV-2, and does not change guideline recommendations against topical therapy for genital disease. 6, 7

Critical Pitfalls to Avoid

• Never use topical therapy as monotherapy for genital HSV-2—it will result in inadequate treatment and prolonged symptoms. 1, 2
• Do not prescribe topical corticosteroids for any HSV infection, as they potentiate viral replication and worsen disease. 4
• If lesions fail to respond to standard oral therapy within 7-10 days, suspect acyclovir resistance and consider intravenous foscarnet (40 mg/kg every 8 hours), not topical alternatives. 2, 5