What is the recommended duration of acyclovir treatment for Herpes Simplex Virus (HSV) encephalitis?

Duration of Acyclovir for HSV Encephalitis

For proven HSV encephalitis, administer intravenous acyclovir for 14-21 days, with strong consideration for the full 21-day course in children aged 3 months to 12 years due to relapse rates as high as 26-29% with shorter durations. 1

Standard Treatment Duration

• Adults and children >12 years: 14-21 days of IV acyclovir at 10 mg/kg every 8 hours 1, 2
• Children 3 months-12 years: Minimum 21 days of IV acyclovir at 500 mg/m² every 8 hours 1
• Neonates: 21 days of IV acyclovir at 20 mg/kg every 8 hours (higher dose has decreased mortality to 5%) 1, 2

The original randomized trials used only 10 days of treatment, but subsequent reports documented clinical relapses, particularly in children where relapse rates reached 26-29% with treatment durations <14 days. 1 This evidence of continuing viral replication in some cases, despite initial treatment, shifted practice toward longer durations. 1

Critical End-of-Treatment Assessment

Perform repeat lumbar puncture at 14-21 days to confirm CSF HSV PCR negativity before discontinuing therapy. 1, 2

• If CSF PCR remains positive for HSV: Continue acyclovir with weekly CSF PCR testing until negative 1, 2
• If CSF PCR is negative: Treatment can be discontinued 1, 2
• A negative CSF PCR at end of therapy is associated with better outcomes 1, 2

This monitoring approach is particularly important in severe disease, immunocompromised patients, or those with previous relapses. 1

Timing Considerations for Optimal Outcomes

Initiate acyclovir within 4 days of symptom onset to achieve mortality reduction from 70% to 8%. 1, 2 Delays beyond 2 days between hospital admission and acyclovir administration are independent predictors of poor outcome. 1, 2

Even with optimal timing and dosing, 18-month mortality remains 28% in adults, with approximately 50% of survivors having permanent sequelae. 2 Predictors of worse outcomes include:

• Age >30 years 1, 2
• Glasgow Coma Score <6 1, 2
• Delayed treatment initiation >4 days 1, 2

Dose Adjustments and Safety Monitoring

Reduce acyclovir dose in patients with pre-existing renal impairment based on creatinine clearance, as the drug is 62-91% renally excreted. 1, 3, 2

Monitor for nephrotoxicity, which manifests after 4 days of IV therapy in up to 20% of patients due to crystalluria and obstructive nephropathy. 1, 3 Risk reduction strategies include:

• Maintaining adequate hydration throughout treatment 1
• Monitoring renal function regularly 3, 2
• Adjusting doses promptly if creatinine rises 1, 3

Rare adverse events include hepatitis, bone marrow failure, and encephalopathy. 1, 3

Common Pitfalls to Avoid

• Do not stop at 10 days: The original trial duration is now considered inadequate given relapse data 1, 4
• Do not skip the repeat LP: Failure to confirm viral clearance can lead to unrecognized persistent infection 1, 2
• Do not use shorter durations in young children: The 3 months-12 years age group has the highest relapse risk (up to 29%) and requires the full 21 days 1
• Do not delay treatment for diagnostic confirmation: Start empiric acyclovir immediately in suspected cases, as CSF PCR remains positive for 7-10 days even after treatment initiation 1