What is the recommended treatment for genital herpes in a person living with HIV, including dosing, duration, and considerations for immunosuppression, renal function, and antiretroviral drug interactions?

Treatment of Genital Herpes in People Living with HIV

For HIV-infected patients with genital herpes, use higher doses and longer durations than in immunocompetent patients: famciclovir 500 mg twice daily for 7 days for episodic treatment, or valacyclovir 500 mg twice daily for chronic suppression. 1, 2

First Episode of Genital Herpes in PLHIV

Initial treatment requires more aggressive therapy than immunocompetent patients:

• Acyclovir 400 mg orally 5 times daily for 7-10 days or until clinical resolution 3
• Alternative: Acyclovir 200 mg orally 5 times daily for 7-10 days 3
• Valacyclovir 1 g twice daily for 7-10 days is preferred for better bioavailability and adherence 4
• Famciclovir 250 mg three times daily for 7-10 days is another option 4

For severe disease requiring hospitalization or with extensive lesions, use intravenous acyclovir 3. HIV-infected patients may have prolonged episodes with extensive disease that necessitate IV therapy 3.

Recurrent Episodes in PLHIV

HIV-infected patients require higher doses than immunocompetent patients for recurrent episodes:

• Famciclovir 500 mg twice daily for 7 days (FDA-approved regimen for HIV patients) 2
• Acyclovir 400 mg orally 3-5 times daily until clinical resolution 3
• Valacyclovir dosing should follow similar principles with higher doses than standard regimens 1

Initiate therapy at the first sign of prodrome (tingling, itching, burning, pain) for maximum benefit 4, 2.

Chronic Suppressive Therapy in PLHIV

For patients with frequent recurrences (≥6 per year), daily suppression is highly effective:

• Valacyclovir 500 mg twice daily is the CDC-recommended regimen for HIV-infected adults 1
• Acyclovir 400 mg twice daily is an alternative 3
• Famciclovir 250 mg twice daily (adjusted from immunocompetent dosing) 2

Suppressive therapy reduces recurrence frequency by at least 75% but does not eliminate asymptomatic viral shedding or transmission risk 3, 1. Patients must continue safer sex practices including condom use even on suppressive therapy 1.

Renal Function Considerations

Dose adjustments are mandatory for renal impairment to prevent acute renal failure:

Famciclovir Dosing by Creatinine Clearance (for HIV patients with recurrent episodes): 2

• CrCl ≥40 mL/min: 500 mg every 12 hours
• CrCl 20-39 mL/min: 500 mg every 24 hours
• CrCl <20 mL/min: 250 mg every 24 hours
• Hemodialysis: 250 mg following each dialysis

For Suppressive Therapy: 2

• CrCl ≥40 mL/min: 250 mg every 12 hours
• CrCl 20-39 mL/min: 125 mg every 12 hours
• CrCl <20 mL/min: 125 mg every 24 hours

Acyclovir-Resistant HSV

Resistance occurs more frequently in immunocompromised patients, particularly those with HIV:

• Acyclovir-resistant strains have been isolated from patients receiving suppressive therapy 3
• All acyclovir-resistant strains are also resistant to valacyclovir, and most to famciclovir 1
• For proven or suspected resistance, switch to foscarnet 40 mg/kg IV every 8 hours until clinical resolution 1
• Topical cidofovir gel 1% applied once daily for 5 consecutive days may be considered as an alternative 5

Monitor for treatment failure: if lesions persist or worsen after 7-10 days of appropriate therapy, suspect resistance and obtain viral culture with susceptibility testing 3.

Antiretroviral Drug Interactions

No significant drug interactions exist between standard antiretrovirals and acyclovir, valacyclovir, or famciclovir based on available evidence. However, both antivirals and certain antiretrovirals (particularly tenofovir) are renally cleared, necessitating careful monitoring of renal function when used concurrently 2.

Critical Pitfalls to Avoid

• Never use topical acyclovir—it is substantially less effective than oral therapy and provides no improvement in systemic symptoms 3, 6
• Do not use immunocompetent dosing regimens in HIV patients—they require higher doses and longer durations 3, 2
• Antiviral therapy does not eradicate latent virus, prevent future recurrences after discontinuation, or eliminate asymptomatic shedding 3, 4, 1
• After 1 year of suppressive therapy, consider interrupting treatment to reassess recurrence rate 3
• High-dose valacyclovir (8 g/day) has been associated with thrombotic microangiopathy in advanced HIV disease and should be avoided 7

Special Considerations for Immunosuppression

The degree of immunosuppression affects treatment approach:

• Patients with CD4 counts <100 cells/μL are at highest risk for severe, prolonged episodes 3
• Consider IV acyclovir for any HIV patient with extensive disease, multi-dermatomal involvement, or visceral complications 3
• Monitor closely for development of resistance, especially in severely immunocompromised patients 4