What are the recommended treatment regimens and dosing for oral and genital herpes simplex virus infection in adults, including primary versus recurrent episodes, immunocompromised status, and renal impairment?

Treatment of Herpes Simplex Virus Infections

For immunocompetent adults with oral or genital herpes, treat first episodes with oral acyclovir 400 mg three times daily for 5-10 days, and recurrent episodes with the same dose for 5 days, initiated at the first sign of prodrome or lesions. 1, 2

First-Episode Genital or Oral Herpes (Immunocompetent Adults)

Oral therapy is the standard of care for first-episode infections, with three equivalent options 1, 2:

• Acyclovir 400 mg orally three times daily for 5-10 days 1, 2
• Acyclovir 200 mg orally five times daily for 5-10 days 1, 2
• Valacyclovir 1 g orally twice daily for 7-10 days 1
• Famciclovir 250 mg orally three times daily for 7-10 days 1

Intravenous acyclovir is reserved for severe mucocutaneous lesions requiring hospitalization, with transition to oral therapy once lesions begin to regress 1. Continue treatment until lesions have completely healed 1.

Critical Timing Consideration

Treatment must be initiated within 2 days of lesion onset for maximum benefit 2. Starting therapy after this window significantly reduces effectiveness 2.

Recurrent Episodes (Immunocompetent Adults)

Episodic treatment for recurrent oral or genital herpes 1, 2:

• Acyclovir 400 mg orally three times daily for 5 days 1, 2
• Acyclovir 200 mg orally five times daily for 5 days 1, 2
• Acyclovir 800 mg orally twice daily for 5 days 2
• Valacyclovir 500 mg orally twice daily for 5 days 1
• Famciclovir 250 mg orally three times daily for 5 days 1

Patients should be provided with medication or a prescription to initiate treatment at the first sign of prodrome or lesions 1. Most immunocompetent patients with recurrent disease experience limited benefit from therapy, particularly if initiated late 2.

Suppressive Therapy (Frequent Recurrences)

Daily suppressive therapy is recommended for patients with ≥6 recurrences per year 1. This reduces recurrence frequency by ≥75% 1.

Suppressive regimens for immunocompetent adults 1:

• Acyclovir 400 mg orally twice daily 1
• Valacyclovir 500 mg orally once daily (for patients with <10 recurrences/year) 1
• Valacyclovir 1 g orally once daily (for patients with ≥10 recurrences/year) 1
• Famciclovir 250 mg orally twice daily 1

After 1 year of continuous suppressive therapy, discontinue treatment to reassess recurrence frequency, as recurrences decrease over time in many patients 1. Suppressive therapy reduces but does not eliminate asymptomatic viral shedding 1.

HIV-Infected and Immunocompromised Patients

HIV-infected patients require higher doses and longer treatment duration 1, 3.

First Episode in HIV-Infected Patients 3:

• Acyclovir 400 mg orally three times daily for 7-10 days 3
• Valacyclovir 1 g orally twice daily for 7-10 days 3
• Extend treatment if healing is incomplete after 10 days 3
• Severe mucocutaneous lesions require IV acyclovir until lesions regress, then switch to oral therapy 1, 3

Recurrent Episodes in HIV-Infected Patients 1, 3:

• Acyclovir 400 mg orally three times daily for 5-10 days 1, 3
• Valacyclovir 500 mg orally twice daily for 5-10 days 3
• Short-course therapy (1-3 days) should NOT be used in HIV-infected patients 1, 3

Suppressive Therapy in HIV-Infected Patients 1, 3:

• Valacyclovir 500 mg orally twice daily is the preferred regimen 1, 3
• Acyclovir 400-800 mg orally 2-3 times daily is an alternative 1
• Daily suppressive therapy decreases HIV viral load in plasma and genital secretions 1, 3

Treatment Failure and Acyclovir Resistance

Suspect acyclovir resistance if lesions do not begin to resolve within 7-10 days of therapy initiation 1, 3. This occurs primarily in immunocompromised patients receiving prolonged suppressive therapy 1.

For suspected resistance 1, 3:

• Obtain viral culture and susceptibility testing 1, 3
• IV foscarnet is the treatment of choice for confirmed acyclovir-resistant HSV 1, 3
• Topical trifluridine, cidofovir, or imiquimod may be used for external lesions, requiring 21-28 days or longer 1

Renal Impairment

Dose adjustments are mandatory for patients with substantial renal impairment to prevent acute renal failure 1, 3. For patients receiving high-dose IV acyclovir, monitor renal function at initiation and once or twice weekly during treatment 1, 3.

Pregnancy

Acyclovir is the first choice for HSV infections in pregnancy due to the most extensive safety data 1. Episodic therapy for first-episode and recurrent disease can be offered during pregnancy 1. Suppressive therapy is not used routinely in pregnancy 1.

Key Counseling Points

• Acyclovir does not eradicate latent virus or affect subsequent recurrence risk after discontinuation 2
• Asymptomatic viral shedding occurs and can transmit infection 1
• Abstain from sexual activity when lesions or prodromal symptoms are present 1
• Condom use should be encouraged during all sexual exposures 1, 3
• Topical acyclovir is substantially less effective than oral therapy and is not recommended 1

Monitoring and Adverse Events

No laboratory monitoring is needed for episodic or suppressive therapy unless substantial renal impairment exists 1, 3. Acyclovir, valacyclovir, and famciclovir are occasionally associated with nausea or headache 1, 3. Thrombotic thrombocytopenic purpura/hemolytic uremic syndrome has been reported with high-dose valacyclovir (8 g/day) in HIV-infected patients but not at standard HSV treatment doses 1.