What is the recommended treatment for herpes simplex virus (HSV) meningitis with acyclovir?

Acyclovir in Viral Meningitis

Direct Recommendation

For HSV meningitis in immunocompetent patients, symptomatic treatment alone is recommended without acyclovir, as these patients recover without neurologic sequelae; however, immunocompromised patients should receive intravenous acyclovir 10 mg/kg every 8 hours for 14-21 days due to significantly improved neurologic outcomes. 1, 2, 3

Critical Distinction: Meningitis vs. Encephalitis

The management of HSV meningitis differs fundamentally from HSV encephalitis:

• HSV encephalitis involves altered mental status, focal neurological deficits, and parenchymal brain involvement—this is a life-threatening condition requiring immediate intravenous acyclovir, which reduces mortality from >70% to <30% 4, 5

• HSV meningitis presents with fever, meningismus, and severe headache without altered consciousness or focal deficits—the British Infection Association explicitly states there is no evidence supporting the use of oral or intravenous acyclovir for herpes meningitis in immunocompetent patients 1, 6

Evidence-Based Treatment Algorithm

For Immunocompetent Patients with HSV Meningitis:

• Provide supportive care with analgesia and fluids 6
• No antiviral therapy is indicated, as all immunocompetent patients in observational studies recovered without neurologic sequelae regardless of treatment 3
• Avoid unnecessary acyclovir to prevent nephrotoxicity (occurs in up to 20% of patients after 4 days of IV therapy) 1, 6

For Immunocompromised Patients with HSV Meningitis:

• Administer intravenous acyclovir 10 mg/kg every 8 hours for 14-21 days 2, 3
• Neurologic outcomes are significantly improved with antiviral therapy in this population (p < 0.05) 3
• Adjust dose for renal impairment, as acyclovir is 62-91% renally excreted 2
• Monitor renal function throughout treatment to prevent crystalluria and obstructive nephropathy 4, 2

For Suspected HSV Encephalitis (Empiric Treatment):

• Start intravenous acyclovir within 6 hours of admission if CSF and/or imaging suggest viral encephalitis 4
• Continue empiric acyclovir even if initial CSF/imaging is normal but clinical suspicion remains high 4
• Dosing: Children 3 months-12 years: 500 mg/m² IV every 8 hours; >12 years and adults: 10 mg/kg IV every 8 hours 4, 2

When to Stop Empiric Acyclovir

Acyclovir can be discontinued in immunocompetent patients if 4, 1:

• An alternative diagnosis has been established, OR
• HSV PCR in CSF is negative on two occasions 24-48 hours apart AND MRI is not characteristic for HSV encephalitis, OR
• HSV PCR in CSF is negative once >72 hours after neurological symptom onset WITH normal consciousness, normal MRI (performed >72 hours after symptom onset), AND CSF white cell count <5×10⁶/L

Duration and Monitoring for Confirmed HSV Encephalitis

• Continue intravenous acyclovir for 14-21 days 4, 2, 5
• Perform repeat lumbar puncture at end of treatment to confirm CSF is negative for HSV by PCR 4, 1
• If CSF remains positive for HSV, continue intravenous acyclovir with weekly CSF PCR until negative 4, 1
• Early treatment (within 4 days of symptom onset) decreases mortality to 8% 2

Critical Pitfalls to Avoid

• Do not use oral acyclovir for CNS herpes infections—oral acyclovir does not achieve adequate CSF levels 4, 1, 6
• Do not treat immunocompetent HSV meningitis with acyclovir—this leads to unnecessary cost, side effects, and false reassurance that may delay identification of alternative diagnoses 1, 6, 3
• Do not stop acyclovir based on a single negative CSF PCR if obtained <72 hours after symptom onset, as early sampling can yield false negatives 4, 1
• Do not confuse recurrent aseptic meningitis with encephalitis—recurrent HSV-2 meningitis is self-limited and does not require treatment in immunocompetent patients 5, 3

Special Populations

Neonates:

• Higher-dose acyclovir (20 mg/kg IV every 8 hours for 21 days) is required, with decreased mortality to 5% 2, 7

HIV-infected patients with severe HSV disease:

• Acyclovir 5 mg/kg IV every 8 hours is recommended 2
• If acyclovir resistance is suspected (persistent lesions despite therapy), consider foscarnet 40 mg/kg IV every 8 hours 2

Adverse Effects Monitoring

• Nephrotoxicity manifests after 4 days of IV therapy in up to 20% of patients 4, 2
• Maintain adequate hydration and monitor creatinine throughout treatment 4, 2
• Rare adverse events include hepatitis, bone marrow suppression, and encephalopathy 4, 2