What is the recommended treatment for Herpes Simplex Virus (HSV) and Herpes Simplex Encephalitis (HSE) encephalitis?

Treatment of Herpes Simplex Virus Encephalitis (HSE)

The standard treatment for HSV encephalitis is intravenous acyclovir at a dose of 10 mg/kg every 8 hours for adults and children >12 years, with a recommended treatment duration of 14-21 days. 1

Dosing Recommendations

Adults and Children >12 years:

• IV acyclovir 10 mg/kg every 8 hours 1

Children 3 months-12 years:

• IV acyclovir 500 mg/m² every 8 hours 1
• Minimum treatment duration of 21 days due to higher relapse rates 1

Neonates:

• IV acyclovir 20 mg/kg every 8 hours 1

Treatment Initiation and Duration

Early initiation of acyclovir therapy is critical for improving outcomes:

• Mortality reduces from >70% to <20-30% with prompt treatment
• Mortality further decreases to 8% if therapy starts within 4 days of symptom onset 1
• Delays in starting treatment are common and associated with poorer outcomes 2
• Treatment should be initiated based on clinical suspicion rather than waiting for confirmatory tests 2

Treatment duration:

• Standard duration: 14-21 days 1
• Minimum 21 days for children 3 months-12 years 1
• Minimum 14 days for confirmed cases 1

Special Considerations

Renal Impairment

• Dose adjustment required in patients with pre-existing renal impairment 1
• Specific adjustments based on creatinine clearance
• Reduced dose and extended interval for creatinine clearance <15 mL/min 1

Geriatric Patients

• Acyclovir plasma concentrations are higher in geriatric patients
• Dosage reduction may be required due to age-related changes in renal function 3

Hydration

• Maintain adequate hydration to prevent crystalluria and obstructive nephropathy 1

Monitoring and Follow-up

• Regular assessment of renal function, neurological status, and fluid balance 1
• Repeat lumbar puncture with HSV PCR testing at the end of treatment to confirm resolution 1
• CSF PCR remains positive for 7-10 days even after starting acyclovir 1

When to Stop Treatment

Acyclovir can be discontinued in immunocompetent patients if:

1. An alternative diagnosis has been made, OR
2. HSV PCR in CSF is negative on two occasions 24-48 hours apart AND MRI is not characteristic for HSV encephalitis, OR
3. HSV PCR in CSF is negative once >72 hours after symptom onset, with unaltered consciousness, normal MRI, and CSF white cell count <5 × 10^6/L 1

Common Pitfalls to Avoid

1. Delaying treatment while waiting for diagnostic confirmation 1, 2
2. Administering incorrect acyclovir dosage 1
3. Stopping treatment based on a single negative CSF PCR 1
4. Using oral acyclovir instead of IV formulation 1
5. Inadequate hydration leading to renal toxicity 1
6. Routine use of corticosteroids (should only be considered in patients with marked cerebral edema or raised intracranial pressure under specialist supervision) 1

Poor Prognostic Factors

• Age >30 years
• Low Glasgow Coma Score (<6)
• Duration of symptoms >4 days before starting acyclovir
• Persistence of confusion, aphasia, or impaired consciousness >5 days 1

Alternative Treatments

In resource-limited settings where IV acyclovir is unavailable or unaffordable, oral valacyclovir at 1,000 mg three times daily may achieve adequate acyclovir concentrations in the CSF 4. However, this should only be considered when IV acyclovir is absolutely unavailable, as IV administration remains the standard of care.