Antiviral Treatment for Herpes Simplex Infection
Primary Oral Herpes Simplex (First Episode)
For primary oral herpes simplex infection in adults, initiate oral acyclovir 200 mg five times daily for 7–10 days until clinical resolution, or alternatively valacyclovir 1000 mg twice daily for 7–10 days. 1
- Treatment must be started during the prodrome or within 2 days of lesion onset for maximum benefit; delayed therapy significantly reduces effectiveness. 1
- Topical acyclovir cream is substantially less effective than oral formulations and should not be used—the CDC explicitly discourages topical therapy for herpes simplex infections. 1
- Acyclovir neither eradicates latent virus nor affects the frequency or severity of future recurrences after discontinuation. 1
Recurrent Oral Herpes Simplex
For recurrent oral herpes (herpes labialis) in immunocompetent adults, use acyclovir 400 mg three times daily for 3–5 days, or valacyclovir 500–1000 mg twice daily for 3–5 days. 2
- Initiate therapy at the first sign of prodromal symptoms (tingling, burning) or within the first 2 days of lesion appearance to achieve meaningful clinical benefit. 1, 2
- A single-dose regimen of famciclovir 1500 mg is FDA-approved for herpes labialis and offers superior convenience. 3
- Most immunocompetent patients with recurrent disease experience limited overall benefit from episodic therapy if treatment is delayed beyond the early prodrome. 1
Suppressive Therapy for Frequent Recurrences
- For patients with frequent recurrences (≥6 episodes per year), daily suppressive therapy with acyclovir 400 mg twice to three times daily or valacyclovir 500–2000 mg twice daily is effective in reducing recurrence frequency. 2, 4
- Sunscreen alone (SPF ≥15) can effectively prevent ultraviolet-triggered recurrent herpes labialis in immunocompetent patients. 2
Pregnant Patients
Pregnant patients with serious HSV-related complications such as disseminated infection, pneumonia, hepatitis, or CNS involvement require intravenous acyclovir 5–10 mg/kg every 8 hours. 1, 5
- For uncomplicated primary or recurrent oral herpes in pregnancy, oral acyclovir 200–400 mg three to five times daily is the preferred agent due to extensive safety data. 1
- Valacyclovir and famciclovir have less pregnancy safety data than acyclovir but may be considered when adherence to five-times-daily dosing is problematic. 4
Immunocompromised Patients
Immunocompromised patients with oral herpes simplex require more aggressive therapy: acyclovir 400 mg orally three to five times daily until clinical resolution, or intravenous acyclovir 5–10 mg/kg every 8 hours for severe, extensive, or disseminated disease. 1, 5
- Immunocompromised hosts may have prolonged episodes with extensive disease requiring IV therapy for disseminated infection, pneumonitis, hepatitis, or CNS complications. 1
- Treatment duration in immunocompromised patients often extends beyond 7–10 days because lesions continue to develop over longer periods (7–14 days) and heal more slowly. 1
- Without adequate antiviral therapy, some immunocompromised patients develop chronic ulcerations with persistent viral replication. 1
Acyclovir-Resistant HSV
- Acyclovir resistance is exceedingly rare in immunocompetent patients but occurs in up to 7% of immunocompromised patients, particularly those on prolonged suppressive therapy. 1, 6
- If lesions fail to improve after 5–7 days of high-dose oral acyclovir (800 mg five times daily), suspect resistance and obtain viral culture with susceptibility testing. 1, 6
- For confirmed acyclovir-resistant HSV, switch to intravenous foscarnet 40 mg/kg every 8 hours (or 60 mg/kg twice daily) for a minimum of 10 days and continue until all lesions have fully healed. 7, 6
- All acyclovir-resistant strains are also resistant to valacyclovir, and most are resistant to famciclovir—do not use these agents after acyclovir failure. 7
- If foscarnet is ineffective or contraindicated, intravenous cidofovir or topical 1–3% cidofovir ointment may be considered. 7, 6
Foscarnet Monitoring
- Obtain baseline renal function (serum creatinine, BUN, creatinine clearance) before the first foscarnet dose and monitor at least twice weekly throughout therapy. 7
- Provide aggressive intravenous hydration (2–3 L per day) to reduce nephrotoxicity. 7
- Check serum calcium, magnesium, phosphate, and potassium at least twice weekly; foscarnet commonly causes hypocalcemia, hypomagnesemia, and hypokalemia requiring replacement. 7
Renal Impairment
All systemic antivirals require dose adjustment in renal impairment because they are eliminated primarily by the kidneys.
Acyclovir Dose Adjustment 5
| Creatinine Clearance | Adjusted Dose |
|---|---|
| >50 mL/min | No adjustment needed |
| 25–50 mL/min | Standard dose every 12 hours |
| 10–25 mL/min | Standard dose every 24 hours |
| <10 mL/min (anuric) | 50% of standard dose every 24 hours |
- Baseline renal function should be assessed before starting therapy; for intravenous acyclovir, monitor renal function at initiation and once or twice weekly during treatment. 5
- Ensure adequate hydration during systemic acyclovir or valacyclovir therapy to reduce the risk of crystalluria and acyclovir-induced nephropathy, which occurs in up to 20% of patients. 1
Valacyclovir Dose Adjustment
| Creatinine Clearance | Adjusted Dose |
|---|---|
| 30–49 mL/min | 500 mg–1 g every 12 hours |
| 10–29 mL/min | 500 mg–1 g every 24 hours |
| <10 mL/min | 500 mg every 24 hours |
Famciclovir Dose Adjustment 3
| Creatinine Clearance | Adjusted Dose |
|---|---|
| ≥60 mL/min | No adjustment needed |
| 40–59 mL/min | 500 mg every 12 hours |
| 20–39 mL/min | 500 mg every 24 hours |
| <20 mL/min | 250 mg every 24 hours |
Key Clinical Pitfalls
- Never rely on topical acyclovir—it is substantially less effective than oral therapy and is explicitly discouraged by the CDC for all herpes simplex infections. 1
- Do not delay treatment—antiviral efficacy is maximal when initiated during the prodrome or within 2 days of lesion onset; most benefit is lost if therapy starts later. 1, 2
- Avoid short-course regimens designed for genital herpes (1–3 days) when treating oral herpes—these are inadequate and may lead to treatment failure. 1
- Screen for immunosuppression in any patient with severe, extensive, or treatment-refractory oral HSV, as acyclovir resistance is rare in immunocompetent hosts but common in immunocompromised patients. 7, 6
- Monitor renal function closely during intravenous acyclovir therapy and adjust dosing promptly for any decline in creatinine clearance to prevent neurotoxicity. 5