What is the appropriate treatment regimen for an adult patient with herpes simplex or varicella-zoster infection, considering their immune status and renal function?

Acyclovir Treatment Guidelines for Herpes Simplex and Varicella-Zoster Infections

Primary Treatment Recommendations

For herpes simplex encephalitis, initiate intravenous acyclovir 10 mg/kg every 8 hours immediately in all patients with suspected encephalitis, as early treatment initiation directly reduces mortality and serious sequelae. 1

Herpes Simplex Virus Infections

Superficial HSV infections:

• Treat with oral acyclovir 200 mg every 4 hours, 5 times daily until all lesions resolve 1, 2
• Alternative: valacyclovir or famciclovir with equivalent efficacy but improved dosing convenience 1

Systemic HSV infections:

• Initiate intravenous acyclovir 10 mg/kg every 8 hours immediately 1
• Reduce immunosuppressive medications concurrently 1
• Continue IV therapy until clinical response occurs, then switch to oral therapy (acyclovir, valacyclovir, or famciclovir) to complete 14-21 days total treatment 1

HSV encephalitis:

• Administer acyclovir 10 mg/kg IV every 8 hours for adults with normal renal function 1
• Use 20 mg/kg IV every 8 hours for neonates 1
• Continue treatment for 14-21 days 1
• Mortality decreases to 8% when therapy begins within 4 days of symptom onset, compared to 28% overall mortality at 18 months 1

Varicella-Zoster Virus Infections

Uncomplicated herpes zoster (shingles):

• First-line: oral acyclovir 800 mg every 4 hours, 5 times daily for 7-10 days 1, 3, 2
• Alternative: valacyclovir 1 gram three times daily for 7 days 3, 4
• Continue treatment until all lesions have completely scabbed 1, 3

Disseminated or invasive herpes zoster:

• Intravenous acyclovir 5-10 mg/kg every 8 hours 3, 4
• Temporarily reduce immunosuppressive medications 1, 3
• Continue IV therapy at least until all lesions have scabbed 1
• Switch to oral therapy once clinical improvement occurs 4

Primary VZV infection (chickenpox):

• Children ≥2 years: 20 mg/kg orally 4 times daily for 5 days (maximum 800 mg per dose) 2
• Adults and children >40 kg: 800 mg orally 4 times daily for 5 days 2
• Immunocompromised patients require intravenous acyclovir 1, 2

Critical Timing Considerations

Initiate antiviral therapy within 72 hours of rash onset for optimal efficacy in reducing acute pain, accelerating lesion healing, and preventing postherpetic neuralgia. 3, 5 Treatment initiated beyond 72 hours shows reduced effectiveness, though immunocompromised patients benefit from treatment regardless of timing 3.

Special Population Adjustments

Immunocompromised Patients

Kidney transplant recipients with superficial HSV:

• Oral acyclovir, valacyclovir, or famciclovir until lesion resolution 1

Kidney transplant recipients with systemic HSV or disseminated VZV:

• Intravenous acyclovir with immunosuppression reduction 1
• Monitor closely for dissemination and visceral complications 3, 4
• Consider extended treatment duration beyond 7-10 days as lesions develop over longer periods (7-14 days) and heal more slowly 3

Severely immunocompromised hosts:

• High-dose IV acyclovir remains treatment of choice for VZV infections 3
• Without adequate therapy, chronic ulcerations with persistent viral replication may develop 3

Renal Impairment

Dose adjustments based on creatinine clearance: 2

• CrCl >10 mL/min: 800 mg every 4 hours (5 times daily)
• CrCl 10-25 mL/min: 800 mg every 8 hours
• CrCl 0-10 mL/min: 800 mg every 12 hours

Hemodialysis patients:

• Administer additional dose after each dialysis session due to 60% decrease in plasma concentrations during 6-hour dialysis 2

Monitor renal function closely during IV therapy:

• Check at initiation and once or twice weekly during treatment 3
• Crystalluria and elevated serum creatinine are the most important adverse effects related to bolus IV administration 6

Post-Exposure Prophylaxis

For varicella-susceptible patients exposed to active VZV infection: 1, 4

• Varicella zoster immunoglobulin (or IVIG) within 96 hours of exposure 1
• If immunoglobulin unavailable or >96 hours elapsed: oral acyclovir for 7 days beginning 7-10 days after exposure 1

Treatment Failures and Resistance

If lesions fail to resolve within 7-10 days:

• Suspect acyclovir resistance 3
• Obtain viral culture with susceptibility testing 3
• Switch to foscarnet 40 mg/kg IV every 8 hours until clinical resolution 3
• All acyclovir-resistant strains are also resistant to valacyclovir, and most to famciclovir 3

Common Pitfalls to Avoid

Do not discontinue treatment at exactly 7 days if lesions are still forming or have not completely scabbed - the clinical endpoint is complete scabbing, not calendar days 3, 5. Short-course therapy designed for genital herpes is inadequate for VZV infection 3.

Do not use topical acyclovir for shingles - it is substantially less effective than systemic therapy and is not recommended 1, 3.

Do not delay treatment pending laboratory confirmation in suspected HSV encephalitis - initiate IV acyclovir immediately as mortality increases significantly with delayed treatment 1.

Do not use corticosteroids during active shingles in immunocompromised patients - this increases risk of severe disease and dissemination 3.