Treatment of Herpes Simplex Virus (HSV) Infections
Oral antiviral therapy with acyclovir, valacyclovir, or famciclovir is the cornerstone of HSV treatment, with specific regimens determined by whether the patient presents with a first episode, recurrent outbreak, or requires suppressive therapy.
First Clinical Episode of Genital Herpes
For first-episode genital herpes, initiate one of the following 7-10 day regimens:
- Valacyclovir 1 g orally twice daily 1
- Acyclovir 400 mg orally three times daily 1
- Acyclovir 200 mg orally five times daily 1
- Famciclovir 250 mg orally three times daily 1
Treatment duration may be extended beyond 10 days if healing is incomplete 1. This is particularly important for patients with severe initial presentations, as 5-30% of first episodes can be severe enough to require hospitalization 2.
Severe Disease Requiring Hospitalization
For severe mucocutaneous HSV lesions, administer intravenous acyclovir until lesions begin to regress, then transition to oral therapy 1. This approach is recommended by the Infectious Diseases Society of America for patients with complications requiring inpatient management 1.
Recurrent Episodes (Episodic Therapy)
For recurrent genital herpes outbreaks, valacyclovir 500 mg orally twice daily for 5 days is the preferred first-line regimen 3, 4.
Alternative Episodic Regimens (all for 5 days):
- Acyclovir 400 mg orally three times daily 3, 4
- Acyclovir 800 mg orally twice daily 3, 4
- Acyclovir 200 mg orally five times daily 3, 4
- Famciclovir 125 mg orally twice daily 3, 4
Critical Timing Considerations
Episodic therapy must be initiated during the prodromal period or within 1 day after onset of lesions to maximize effectiveness 3, 4. Delayed treatment beyond 72 hours significantly reduces efficacy 3. Patients should be provided with medication to self-initiate at the first sign of prodrome 4.
Common Pitfall to Avoid
Topical acyclovir is substantially less effective than oral therapy and should not be used 2, 3, 4. This is a key error to avoid, as topical formulations provide minimal clinical benefit compared to systemic treatment 2.
Suppressive Therapy (Chronic Daily Therapy)
Suppressive therapy should be offered to patients with frequent recurrences (≥6 episodes per year) 1, 3, 4.
Recommended Suppressive Regimens:
- Valacyclovir 1 g orally once daily (for frequent recurrences, ≥10 episodes/year) 1
- Valacyclovir 500 mg orally once daily (for infrequent recurrences, <10 episodes/year) 1
- Acyclovir 400 mg orally twice daily 1, 4
- Famciclovir 250 mg orally twice daily 4
Benefits of Suppressive Therapy
Suppressive therapy reduces recurrence frequency by ≥75% and reduces asymptomatic viral shedding, which may decrease transmission risk 1, 3. Valacyclovir is the only antiviral FDA-approved for once-daily suppressive dosing, which may improve adherence 5.
Duration and Reassessment
After 1 year of suppressive therapy, consider discontinuation to reassess recurrence frequency 3, 4. Suppressive therapy is safe for up to 6 years with acyclovir and at least 1 year with valacyclovir 4.
Special Populations
HIV-Infected Patients
HIV-infected patients require higher doses and longer treatment duration 1, 4. For recurrent episodes in HIV-infected adults, use 500 mg twice daily for 7 days 1. For suppressive therapy in HIV-infected patients, use valacyclovir 500 mg twice daily 1. Short-course therapy (1-3 days) should not be used in HIV-infected patients 1.
HIV-infected patients may experience treatment failures with any regimen and require close monitoring 2. Healing is slower among HIV-infected patients, and some experts suggest using 7-day erythromycin regimens for certain conditions 2.
Pregnant Women
Acyclovir is the first-choice antiviral for HSV infections during pregnancy based on decades of safety data showing no pattern of adverse pregnancy outcomes 1. Episodic therapy for first-episode HSV disease and recurrences can be offered during pregnancy 1.
For women with a history of genital herpes, suppressive therapy starting at 36 weeks gestation may be considered to reduce HSV shedding at delivery and decrease the need for cesarean delivery 1. However, suppressive therapy is NOT routinely recommended during pregnancy for women without frequent or severe recurrences 1.
Cesarean delivery is recommended for women with genital herpes prodrome or visible lesions at the onset of labor 1. This is critical for preventing neonatal transmission, which occurs primarily through maternal genital shedding at delivery 1.
Treatment Failure and Acyclovir Resistance
Suspect treatment failure if lesions do not begin to resolve within 7-10 days after initiation of therapy 1, 4. In such cases, viral culture and susceptibility testing should be performed 1.
For proven or suspected acyclovir-resistant HSV, intravenous foscarnet 40 mg/kg every 8 hours is the treatment of choice 1, 4, 6. Acyclovir-resistant strains are routinely resistant to ganciclovir as well 2. Resistance is more common in immunocompromised patients, particularly those with HIV 6, 7.
Comparative Efficacy: Valacyclovir vs. Famciclovir
Valacyclovir appears to be somewhat more effective than famciclovir for suppression of genital herpes and viral shedding 8. In a comparative trial, HSV was detected on 3.2% of days among famciclovir recipients versus 1.3% of days among valacyclovir recipients (relative risk 2.33,95% CI 1.18-4.89) 8. Time to first virologically confirmed recurrence was also shorter among famciclovir recipients 8.
Patient Counseling Essentials
Patients must be counseled that genital herpes is a recurrent, incurable viral disease 4. Antiviral medications control symptoms but do not eradicate latent virus or affect recurrence risk after discontinuation 2, 3.
Key Counseling Points:
- Abstain from sexual activity when lesions or prodromal symptoms are present 4
- Use condoms during all sexual exposures with new or uninfected partners 4
- Asymptomatic viral shedding can occur, potentially leading to transmission even without visible lesions 4
- Inform sex partners about having genital herpes 4
Monitoring Requirements
No laboratory monitoring is needed in patients receiving episodic or suppressive therapy unless they have substantial renal impairment 1. For patients with renal impairment, dosage adjustment based on creatinine clearance is required 9. Monitoring of renal function is recommended at initiation and once or twice weekly during treatment for patients receiving high-dose IV acyclovir 1.