Acyclovir Dosing for HSV and VZV Infections
Neonatal HSV Disease
Neonatal HSV requires high-dose intravenous acyclovir at 20 mg/kg every 8 hours for 21 days for CNS or disseminated disease, and 14 days for skin, eye, and mouth disease. 1
- Do not discontinue therapy in neonates with CNS disease unless a repeat CSF HSV DNA PCR is negative at day 19–21 of treatment 1
- The higher neonatal dose (20 mg/kg vs. 10 mg/kg) has decreased mortality to 5%, with approximately 40% of survivors developing normally 1
- Major toxicity in neonates is neutropenia (absolute neutrophil count <1,000/mm³), occurring in the context of high-dose therapy 1
- Long-term oral suppressive therapy following neonatal treatment (300 mg/m² body surface area 2–3 times daily) has been associated with 46% neutropenia rates, though usually self-limited 1
Herpes Simplex Encephalitis
For herpes simplex encephalitis in adults and children beyond the neonatal period, administer intravenous acyclovir 10 mg/kg every 8 hours for 14–21 days. 1
- Mortality at 18 months remains 28% despite treatment, but decreases to 8% if therapy is initiated within 4 days of symptom onset 1
- Predictors of adverse outcome include age ≥30 years, Glasgow coma score <6, and symptom duration ≥4 days before starting acyclovir 1
- A delay of ≥2 days between hospital admission and acyclovir administration is an independent predictor of poor outcome 1
- Obtain a repeat CSF PCR at the end of therapy in patients without appropriate clinical response; if positive, continue antiviral therapy 1
- Relapse rates of approximately 5% have been reported in children and adults, with 8% relapse in neonates treated with 10 mg/kg for 10 days (no relapses documented with 20 mg/kg for 21 days) 1
Primary Genital Herpes
Immunocompetent Patients
For first-episode genital herpes in immunocompetent adults, prescribe oral acyclovir 200 mg five times daily for 7–10 days (or until lesions resolve). 1
- Treatment effect is maximized by early initiation, preferably during the prodromal period 2, 3
- Intravenous acyclovir is effective for initial genital herpes in normal hosts but is reserved for severe disease requiring hospitalization 4
HIV-Infected Patients
For initial genital herpes in HIV-infected adults, use oral acyclovir 400 mg five times daily for 7–10 days (or until lesions resolve), which is a stronger regimen than for immunocompetent patients. 5
- An alternative lower dose of 200 mg five times daily for 7–10 days may be used when higher dosing is not feasible 5
- Intravenous acyclovir is indicated for severe disease, extensive lesions, or multi-dermatomal involvement 5
Recurrent Genital Herpes
Episodic Therapy in Immunocompetent Patients
For recurrent genital herpes episodes in immunocompetent patients, standard episodic therapy regimens apply, though specific dosing is not detailed in the highest-quality guidelines provided.
Episodic Therapy in HIV-Infected Patients
For recurrent genital herpes in HIV-infected individuals, use oral acyclovir 400 mg three to five times daily until clinical resolution. 5
- This higher dosing (compared to immunocompetent hosts) reflects the prolonged and severe nature of episodes in immunocompromised patients 1, 5
- For severe cases, acyclovir 5 mg/kg IV every 8 hours may be required 1
Chronic Suppressive Therapy for Genital Herpes
For frequent recurrences (≥6 per year) in HIV-infected adults, prescribe oral acyclovir 400 mg twice daily for chronic suppression. 5
- Daily suppressive therapy reduces recurrence frequency by at least 75% but does not eliminate asymptomatic viral shedding or transmission risk 5
- In immunocompetent patients, oral acyclovir has prevented recurrence in >70% during suppressive therapy 2
- After one year of continuous suppressive therapy, consider a treatment interruption to reassess the recurrence rate 5
- Acyclovir-resistant HSV strains have been isolated from HIV-infected patients receiving suppressive therapy; if lesions persist after 7–10 days of appropriate therapy, suspect resistance and obtain viral culture with susceptibility testing 5, 6
Mucocutaneous HSV in Immunocompromised Patients
For symptomatic HSV gingivostomatitis in HIV-infected children, administer intravenous acyclovir 5–10 mg/kg every 8 hours or oral acyclovir 20 mg/kg every 8 hours for 7–14 days. 1
- HIV-infected children with severe oral HSV recurrences (>3–6 severe episodes per year) can be considered for secondary suppressive therapy with oral acyclovir 1
For immunocompromised adults with localized mucocutaneous HSV, use oral valacyclovir 1 gram twice daily for 7–10 days and continue until all lesions have completely healed, which may require extending therapy beyond 10 days. 6
- Oral acyclovir 400 mg 3–5 times daily until clinical resolution is an alternative if valacyclovir is unavailable 6
- Escalate immediately to IV acyclovir 5–10 mg/kg every 8 hours for severe, disseminated, or visceral HSV 6
Herpes Labialis (Cold Sores)
Specific acyclovir dosing for herpes labialis in immunocompetent patients is not detailed in the highest-quality guidelines provided; topical acyclovir is not recommended as it is substantially less effective than oral therapy. 6
Herpes Zoster (Shingles)
Immunocompetent Patients
For uncomplicated herpes zoster in immunocompetent adults, prescribe oral acyclovir 800 mg five times daily for 7–10 days, continuing until all lesions have scabbed. 7
- Treatment must be initiated within 72 hours of rash onset for optimal efficacy in reducing acute pain, accelerating lesion healing, and preventing postherpetic neuralgia 7
- Do not discontinue at exactly 7 days if lesions are still forming or have not completely scabbed 7
- Valacyclovir 1 gram three times daily or famciclovir 500 mg three times daily offer better bioavailability and less frequent dosing, potentially improving adherence 7
Immunocompromised Patients
For herpes zoster in immunocompromised patients (e.g., chemotherapy, HIV, organ transplant), administer intravenous acyclovir 10 mg/kg every 8 hours for at least 7–10 days and until all lesions have completely scabbed. 7
- Intravenous therapy is mandatory for immunocompromised patients due to high risk of dissemination and complications 7
- Consider temporary reduction or discontinuation of immunosuppressive medications in disseminated or invasive herpes zoster if clinically feasible 7
- Immunocompromised patients may develop new lesions for 7–14 days and heal more slowly, requiring treatment extension well beyond 7–10 days 7
Disseminated or Complicated Herpes Zoster
For disseminated herpes zoster (≥3 dermatomes, visceral involvement, hemorrhagic lesions), CNS complications, or complicated ocular/facial disease, use intravenous acyclovir 10 mg/kg every 8 hours. 7
- Disseminated zoster requires both airborne and contact precautions in healthcare settings 7
- Continue treatment until clinical resolution is attained, meaning all lesions have completely scabbed 7
Varicella (Chickenpox)
Use of oral acyclovir for varicella in otherwise healthy individuals is effective but controversial, and in some countries it is recommended only for potentially severe cases. 2
- High-dose IV acyclovir remains the treatment of choice for VZV infections in severely compromised hosts 7
Acyclovir-Resistant HSV and VZV
For proven or suspected acyclovir-resistant HSV or VZV, switch to intravenous foscarnet 40 mg/kg every 8 hours until clinical resolution. 1, 6, 7
- All acyclovir-resistant strains are cross-resistant to valacyclovir, and most are resistant to famciclovir 1, 6
- Topical cidofovir 1% gel applied once daily for 5 consecutive days may be effective for resistant lesions 1, 6
- Do not switch to famciclovir or increase valacyclovir dose, as these will not overcome true acyclovir resistance 6
- Patients with suspected or confirmed resistance should be managed in consultation with an infectious disease specialist 6
Renal Dose Adjustments
Acyclovir is primarily excreted by the kidney; dose adjustment based on creatinine clearance is mandatory in patients with renal insufficiency or renal failure. 1
- Monitor renal function at treatment initiation and once or twice weekly during IV acyclovir therapy 7
- Ensure adequate hydration during systemic acyclovir or valacyclovir therapy to reduce the risk of crystalluria and acyclovir-induced nephropathy 7
- Primary toxicities include phlebitis, renal toxicity, nausea, vomiting, and rash 1
- In immunocompromised patients receiving high-dose therapy, assess for thrombotic thrombocytopenic purpura/hemolytic uremic syndrome 7
Critical Pitfalls to Avoid
- Topical acyclovir should not be used for genital herpes or shingles in any patient population, as it is substantially less effective than systemic therapy. 5, 6, 7
- Immunocompetent dosing regimens (lower doses, shorter courses) must not be applied to HIV-infected or immunocompromised patients; higher doses and longer durations are required. 5
- Short-course antiviral regimens of 1–3 days designed for genital herpes are inadequate for VZV infection and should be avoided. 7
- Do not stop treatment at exactly 7 days if lesions are still active; continue until all lesions have scabbed or healed. 1, 7
- Antiviral therapy does not eradicate latent HSV or VZV, prevent future recurrences after discontinuation, or eliminate asymptomatic shedding. 5, 2, 4, 3
- Non-adherence to the prescribed regimen can mimic true antiviral resistance and should be evaluated before changing therapy. 6