What are the recommended acyclovir dosing regimens for herpes simplex virus (HSV) and varicella‑zoster virus (VZV) infections in immunocompetent adults, immunocompromised adults, pediatric patients, and patients with impaired renal function, and what alternative oral antivirals can be used?

Acyclovir Dosing for HSV and VZV Infections

Herpes Zoster (Shingles) in Immunocompetent Adults

For uncomplicated herpes zoster in immunocompetent adults, oral acyclovir 800 mg five times daily for 7-10 days is the standard regimen, with treatment continuing until all lesions have completely scabbed. 1

• Initiate therapy within 72 hours of rash onset for optimal efficacy in reducing acute pain, accelerating lesion healing, and preventing postherpetic neuralgia 1
• Valacyclovir 1000 mg three times daily or famciclovir 500 mg three times daily offer superior bioavailability and less frequent dosing, potentially improving adherence 1
• Do not discontinue treatment at exactly 7 days if lesions are still forming or have not completely scabbed—the clinical endpoint is complete crusting, not an arbitrary duration 1

Herpes Zoster in Immunocompromised Patients

High-dose intravenous acyclovir 10 mg/kg every 8 hours is the treatment of choice for VZV infections in severely immunocompromised hosts, continuing for a minimum of 7-10 days and until all lesions have completely scabbed. 2, 1

• Immunocompromised patients include those receiving active chemotherapy, HIV-infected individuals, organ transplant recipients, and patients on chronic immunosuppressive agents 1
• Oral therapy should be reserved only for mild cases in patients with transient immunosuppression or to complete therapy after clinical response to IV acyclovir 2
• Consider temporary reduction or discontinuation of immunosuppressive medications in cases of disseminated or invasive herpes zoster if clinically feasible 1
• Immunocompromised patients may develop new lesions for 7-14 days and heal more slowly, often requiring treatment extension well beyond 10 days 1

Prophylaxis in High-Risk Immunocompromised Patients

• Allogeneic blood and bone marrow transplant recipients routinely receive acyclovir 800 mg twice daily or valacyclovir 500 mg twice daily during the first year after transplantation 2
• Patients receiving proteasome inhibitor-based therapies (e.g., bortezomib) should receive acyclovir 400 mg daily or valacyclovir prophylaxis 1

Genital Herpes Simplex in Immunocompetent Adults

For first-episode genital herpes in immunocompetent adults, oral acyclovir 400 mg three times daily or 200 mg five times daily for 7-10 days is effective. 3

• For recurrent episodes, acyclovir 400 mg three times daily for 5 days or 800 mg twice daily for 5 days 3
• Chronic suppressive therapy with acyclovir 400 mg twice daily totally suppresses recurrences in the majority of patients with frequent episodes (≥6 per year) 3, 4
• Suppressive therapy reduces recurrence frequency by at least 75% but does not eliminate asymptomatic viral shedding or transmission risk 5

Genital Herpes Simplex in HIV-Infected Patients

HIV-infected adults with first-episode genital herpes require higher dosing: oral acyclovir 400 mg five times daily for 7-10 days (or until lesions resolve). 5

• For recurrent episodes in HIV-infected patients, use acyclovir 400 mg three to five times daily until clinical resolution—higher than immunocompetent dosing 5
• Chronic suppressive therapy: acyclovir 400 mg twice daily for patients with frequent recurrences 5
• Intravenous acyclovir is indicated for severe disease requiring hospitalization, extensive lesions, or multi-dermatomal involvement 5

Mucocutaneous HSV in Immunocompromised Patients

For localized mucocutaneous HSV in immunocompromised patients, oral valacyclovir 1 gram twice daily for 7-10 days and until all lesions have completely healed is preferred. 6

• Alternative: acyclovir 400 mg orally 3-5 times daily if valacyclovir is unavailable 6
• Immunocompromised patients often require extended therapy beyond 10 days because lesions develop over longer periods and heal more slowly 6
• Escalate immediately to IV acyclovir 5-10 mg/kg every 8 hours for severe, disseminated, or visceral HSV 6

Pediatric Dosing

For varicella (chickenpox) in immunocompromised children, intravenous acyclovir 500 mg/m² or 10 mg/kg every 8 hours is effective, causing more rapid resolution and fewer complications. 7

• Oral acyclovir 800 mg five times daily (for adolescents/older children with herpes zoster) follows adult dosing when appropriate 7
• Neonatal HSV infections require intravenous acyclovir 4

Renal Dose Adjustments

Baseline renal function must be assessed at treatment initiation, with monitoring once or twice weekly during IV therapy; dose adjustments are mandatory for renal impairment to prevent acute renal failure. 1, 6

• For oral acyclovir with CrCl 10-25 mL/min: reduce frequency to every 12 hours 7
• For oral acyclovir with CrCl <10 mL/min: reduce frequency to every 24 hours 7
• Maintain adequate hydration and urine flow during high-dose therapy (500 mg/m² or 10 mg/kg IV) 7

Acyclovir-Resistant Infections

For proven or suspected acyclovir-resistant HSV or VZV, switch to intravenous foscarnet 40 mg/kg every 8 hours until clinical resolution. 1, 5, 6

• Suspect resistance when lesions persist or fail to improve after 7-10 days of appropriate antiviral therapy 6
• All acyclovir-resistant strains are cross-resistant to valacyclovir, and most are resistant to famciclovir 1, 6
• Acyclovir resistance is rare in immunocompetent patients but occurs in up to 7% of immunocompromised patients 1
• Alternative: topical cidofovir 1% gel applied once daily for 5 consecutive days 1

Critical Pitfalls to Avoid

• Topical acyclovir is substantially less effective than systemic therapy and is not recommended for HSV or VZV infections 2, 1, 5
• Do not use immunocompetent dosing regimens (lower doses, shorter courses) in HIV-infected or immunocompromised patients—higher doses and longer durations are required 5
• Antiviral therapy does not eradicate latent virus, prevent future recurrences after discontinuation, or eliminate asymptomatic shedding 5, 8, 4
• Monitor mental status during high-dose therapy, as neurotoxicity can occur 7