What is the appropriate treatment for herpes, including considerations for severity and patient immune status?

Treatment for Herpes

For genital herpes, treat initial episodes with valacyclovir 1 gram twice daily for 10 days, recurrent episodes with 500 mg twice daily for 3 days, and offer suppressive therapy (500 mg once daily for ≤9 recurrences/year or 1 gram once daily for ≥10 recurrences/year) to all HSV-2-infected patients. 1, 2

Initial Episode of Genital Herpes

• Valacyclovir 1 gram twice daily for 10 days is the recommended treatment, most effective when started within 48 hours of symptom onset 2
• Alternative options include famciclovir or acyclovir 400 mg orally five times daily for 7-10 days 3
• Do not use short-course therapy (1-3 days) in any patient with genital herpes, as these regimens are designed for immunocompetent patients and are inadequate 3

Recurrent Episodes of Genital Herpes

• Valacyclovir 500 mg twice daily for 3 days initiated at first sign of recurrence 2
• Alternative: Famciclovir 1 gram twice daily for 1 day (single-day therapy) 4
• Alternative: Acyclovir 400 mg orally five times daily for 5 days 3
• Treatment should be initiated within 6 hours of symptom onset for maximum benefit 4

Suppressive Therapy for Genital Herpes

Immunocompetent Patients

• For patients with ≤9 recurrences per year: Valacyclovir 500 mg once daily 1, 2, 5
• For patients with ≥10 recurrences per year: Valacyclovir 1 gram once daily 1, 5
• Alternative: Acyclovir 400 mg twice daily 3, 5
• Alternative: Famciclovir 250 mg twice daily 6
• Suppressive therapy reduces recurrences by ≥75% and has documented safety for up to 6 years with acyclovir and 1 year with valacyclovir 1

HIV-Infected Patients

• Valacyclovir 500 mg twice daily for patients with CD4+ count ≥100 cells/mm³ 3, 1, 2
• This regimen also decreases HIV concentration in plasma and genital secretions 3, 1
• Never use once-daily dosing in HIV-infected patients—twice-daily regimens are mandatory 3

Monitoring and Duration

• No laboratory monitoring needed unless substantial renal impairment exists 3, 1
• After 1 year of continuous suppressive therapy, consider discussing discontinuation to reassess recurrence frequency 1
• Suppressive therapy reduces but does not eliminate asymptomatic viral shedding 1

Orolabial Herpes (Cold Sores)

• Valacyclovir 2 grams twice daily for 1 day (12 hours apart) initiated at earliest symptom 2
• Alternative: Acyclovir, famciclovir, or valacyclovir for 5-10 days 3
• Treatment of recurrent orolabial herpes is of questionable benefit as episodes tend to be mild and infrequent 6

Severe Mucocutaneous HSV Disease

• IV acyclovir is the treatment of choice for severe mucocutaneous lesions 3
• Switch to oral therapy after lesions begin to regress 3
• Continue therapy until lesions have completely healed 3
• Monitor renal function at initiation and once or twice weekly during IV treatment 3

Treatment Failure and Acyclovir Resistance

Suspecting Resistance

• Suspect resistance if lesions do not begin to resolve within 7-10 days of therapy initiation 3
• Obtain viral culture and susceptibility testing if resistance suspected 3
• Resistance is extremely rare (<0.5%) in immunocompetent patients but occurs in 5-7% of immunocompromised patients 1, 7

Treatment of Acyclovir-Resistant HSV

• IV foscarnet 40 mg/kg every 8 hours until clinical resolution is the treatment of choice 3, 8
• All acyclovir-resistant strains are also resistant to valacyclovir, and most are resistant to famciclovir 1, 8
• For accessible external lesions: Topical cidofovir 1% gel once daily for 5 consecutive days 8
• Alternative topical options: Trifluridine or imiquimod (may require 21-28 days or longer) 3

Treatment Algorithm for Suspected Resistance

1. If standard oral acyclovir 200 mg five times daily fails after 3-5 days, increase to 800 mg five times daily 7
2. If no response after 5-7 days at high-dose oral therapy, switch to alternative agents (not IV acyclovir) 7
3. Obtain repeat cultures for viral, fungal, and bacterial pathogens 7
4. Order acyclovir susceptibility studies if available 7
5. For accessible lesions: Apply topical trifluridine 3-4 times daily until healed 7
6. For inaccessible lesions or TFT failure: IV foscarnet 40 mg/kg three times daily for 10 days 7

Special Populations

Pregnancy

• Acyclovir is the first choice for HSV infections in pregnancy due to most extensive safety data 3
• Episodic therapy for first-episode and recurrences can be offered during pregnancy 3
• Suppressive therapy is not used routinely in pregnancy 3
• The risk of HSV transmission to newborn is low in HSV-2-seropositive women unless genital HSV acquired in late pregnancy 3

Renal Impairment

• Dose adjustment necessary for creatinine clearance <50 mL/min 1
• For CrCl 30-49 mL/min with valacyclovir suppression, no dose reduction needed 1
• Monitor renal function closely during IV acyclovir therapy 3

Acyclovir Allergy

• IV foscarnet 40 mg/kg every 8 hours until clinical resolution 8
• For mild localized disease: Topical cidofovir 1% gel once daily for 5 consecutive days 8
• Desensitization to acyclovir is possible in consultation with allergy specialist 8

Important Caveats

• Avoid high-dose valacyclovir (8 grams/day) in immunocompromised patients due to risk of thrombotic thrombocytopenic purpura/hemolytic uremic syndrome 3, 1
• Short-course therapy should never be used in HIV-infected patients 3
• Topical antiviral therapy is substantially less effective than systemic therapy and is not recommended 3
• Patients should abstain from sexual activity while lesions are present 8
• Condom use should be encouraged during all sexual exposures, as transmission can occur during asymptomatic periods 8