What is the role of Acyclovir (antiviral medication) in post-exposure prophylaxis for varicella?

Role of Acyclovir in Post-Exposure Prophylaxis for Varicella

Acyclovir is not recommended for post-exposure prophylaxis in otherwise healthy individuals exposed to varicella, as vaccination is the preferred method for these populations and varicella-zoster immune globulin (VZIG) is recommended for high-risk individuals. 1

Primary Recommendations for Post-Exposure Prophylaxis

• For immunocompromised patients, pregnant women, and other high-risk individuals without evidence of immunity, VZIG is the recommended first-line post-exposure prophylaxis, administered within 96 hours of exposure 1
• Vaccination is the method of choice for post-exposure prophylaxis in healthy individuals without evidence of immunity 1
• No studies have been conducted regarding prophylactic use of acyclovir among immunocompromised persons; therefore, VZIG remains the recommended intervention in these situations 1

High-Risk Populations Requiring Post-Exposure Prophylaxis

• Immunocompromised patients (primary and acquired immune deficiency disorders, neoplastic diseases, transplant recipients) 1
• Neonates whose mothers have signs and symptoms of varicella around delivery 1
• Pregnant women without evidence of immunity 1
• Patients on steroid therapy (doses >2 mg/kg of body weight or total of 20 mg/day of prednisone or equivalent) 1

Evidence on Acyclovir for Post-Exposure Prophylaxis

• Recent data from 2022 suggests that antiviral agents (acyclovir/valacyclovir) administered as PEP are effective and safe for preventing VZV infections in immunocompromised patients, with significantly lower incidence of secondary VZV infection compared to no prophylaxis (2.2% vs 20.0%, P=0.036) 2
• However, a 2024 study found that among high-risk children receiving different forms of PEP, those receiving acyclovir had higher rates of subsequent varicella disease (15.4%) compared to those receiving VZIG (3.4%) or IVIG (0%) 3
• For patients who received 2 doses of varicella vaccine and later became immunocompromised, VZIG is not indicated, but they should be monitored closely and acyclovir treatment should be instituted at the earliest signs or symptoms of disease 1

Specific Scenarios for Acyclovir Use

• For immunocompromised children exposed to varicella, acyclovir may be considered as an adjunctive measure to VZIG 4
• In HIV-infected individuals who are susceptible to VZV, VZIG is recommended within 96 hours after exposure, as data are lacking regarding the effectiveness of acyclovir for preventing chickenpox in this population 1
• For VZV-susceptible, HIV-infected pregnant women exposed to VZV, VZIG is recommended within 96 hours after exposure; if oral acyclovir is used, VZV serology should be performed so the drug can be discontinued if the patient is seropositive for VZV 1

Acyclovir Treatment vs. Prophylaxis

• Acyclovir is FDA-approved for the treatment of chickenpox in children (2 years and older) and adults, with dosing of 20 mg/kg per dose (up to 800 mg) orally 4 times daily for 5 days 5
• Acyclovir is effective in reducing the duration and severity of clinical illness if administered within 24 hours of rash onset 1
• Intravenous acyclovir is indicated for the treatment of varicella-zoster infections in immunocompromised patients 5

Important Caveats and Pitfalls

• Acyclovir prophylaxis does not decrease transmission of varicella or reduce duration of absence from school 1
• Timing is critical - treatment with acyclovir should be initiated at the earliest sign or symptom of chickenpox, as there is no information about efficacy when initiated more than 24 hours after onset of signs and symptoms 5
• In patients with renal impairment, the dose of acyclovir should be modified based on creatinine clearance 5
• The decision to use acyclovir "off-label" for prophylaxis requires careful benefit-risk assessment, especially in children 6

Conclusion for Clinical Practice

• For post-exposure prophylaxis in high-risk individuals, VZIG remains the first-line recommendation within 96 hours of exposure 1
• If VZIG is unavailable or administration is delayed beyond 96 hours, acyclovir prophylaxis may be considered in immunocompromised patients, though evidence for this approach is limited 2, 4
• For otherwise healthy individuals, vaccination is preferred over acyclovir for post-exposure prophylaxis 1