What is the recommended antiviral treatment for varicella in otherwise healthy children, adolescents, and adults compared with immunocompromised patients (e.g., those receiving chemotherapy, transplant recipients, HIV infection with CD4 count <200 cells/µL, or on high‑dose steroids)?

Antiviral Treatment for Varicella: Immunocompetent vs. Immunocompromised Patients

For otherwise healthy children and adolescents with varicella, oral acyclovir is only recommended for those at increased risk (age >12 years, chronic lung/skin disease, long-term salicylate therapy) and must be started within 24 hours of rash onset; however, for immunocompromised patients (chemotherapy, transplant, HIV with CD4 <200, high-dose steroids), intravenous acyclovir is mandatory and must be initiated immediately—within 24 hours—to prevent life-threatening complications. 1

Treatment Algorithm by Patient Population

Healthy Children (<12 years)

• No routine antiviral treatment is recommended for otherwise healthy children under 12 years with uncomplicated varicella 1
• Treatment is not indicated unless the child has chronic cutaneous or pulmonary disorders, or is receiving long-term salicylate therapy 1
• Post-exposure vaccination within 3 days is >90% effective at preventing disease and should be the primary intervention for susceptible healthy children 1

Healthy Adolescents and Adults (≥12 years)

• Oral acyclovir 800 mg four times daily for 5 days is recommended for otherwise healthy persons aged >12 years, but only if initiated within 24 hours of rash onset 1, 2
• Alternative dosing for adolescents/adults over 40 kg: 800 mg orally 4 times daily for 5 days 2
• The clinical benefit includes decreased duration of new lesion formation, reduced fever duration, and decreased symptom severity 1

Immunocompromised Patients: High-Risk Categories

The following patients require immediate intravenous acyclovir:

• Patients receiving chemotherapy or with neoplastic diseases 1
• Solid organ transplant recipients 1, 3
• HIV infection with CD4 count <200 cells/µL 4, 5
• Patients on high-dose corticosteroids (≥20 mg/day prednisone equivalent for ≥2 weeks) 1
• Patients receiving purine analogues, methotrexate, or biologic therapies 1
• Patients with primary immunodeficiency disorders 1

Immunocompromised Treatment Protocol

Intravenous acyclovir is the standard of care and must be started within 24 hours of rash onset to effectively reduce varicella-associated morbidity and mortality 1

• Dosing: The evidence demonstrates clear benefit when acyclovir is administered within the first 24 hours, with proven reduction in complications and death rates 1
• Duration: Treatment continues until clinical resolution is attained 6
• Monitoring: HIV-infected individuals should be monitored closely and treated at earliest signs 1

Critical Distinction: Oral vs. IV Therapy

The key difference between immunocompetent and immunocompromised patients is route of administration:

• Oral acyclovir failures occurred exclusively in patients with CD4 counts below 100/mm³ 5
• Intravenous acyclovir should be reserved for severe disseminated and/or neurological forms and for highly immunodepressed patients (CD4 count below 200/mm³) 5
• Live varicella vaccine is absolutely contraindicated in highly immunocompromised patients and can cause severe disseminated disease requiring prolonged hospitalization 4, 3

Post-Exposure Prophylaxis: Different Strategies by Immune Status

Healthy Individuals

• Post-exposure varicella vaccination within 3 days is >90% effective at preventing disease and should be the first-line approach 1
• If given within 5 days, vaccination remains 70% effective at preventing disease and 100% effective at modifying severe disease 1

Immunocompromised Patients

• VariZIG (varicella zoster immune globulin) should be administered within 96 hours (ideally as soon as possible) after exposure 1
• Dosing: 125 units/10 kg body weight (maximum 625 units) administered intramuscularly 1
• VariZIG is indicated for immunocompromised patients without evidence of immunity, including those with HIV infection with CD4 <200 cells/µL 4, 1
• Alternative if VariZIG unavailable: A 7-day course of oral acyclovir beginning 7-10 days after varicella exposure 6, 1

Specific High-Risk Groups Requiring VariZIG

• Immunocompromised patients without evidence of varicella immunity 4, 1
• Pregnant women without immunity 1
• Neonates whose mothers developed varicella 5 days before to 2 days after delivery 1
• Premature infants 1

Special Populations

Pregnant Women

• For pregnant women with serious varicella complications (particularly pneumonia), intravenous acyclovir should be considered despite limited controlled data 1
• Acyclovir is FDA Category B (animal studies show no teratogenic effects) 1
• A prospective registry of 596 first-trimester exposures showed birth defect rates approximating the general population 1

HIV-Infected Patients: Vaccination Considerations

• HIV-infected children aged 1-8 years with CD4 cell percentages ≥15% may be considered for varicella vaccination with 2 doses given 3 months apart 4, 1
• HIV-infected persons aged >8 years with CD4+ T-lymphocyte count >200 cells/µL may also be considered for vaccination (2 doses, 3 months apart) 4, 1
• If HIV-infected persons develop clinical varicella despite vaccination, acyclovir may modify disease severity 1

Renal Dose Adjustments

For patients with renal impairment, acyclovir dosing must be modified 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: Administer additional dose after each dialysis 2

Critical Caveats and Common Pitfalls

Timing Is Everything

• Acyclovir must be initiated within 24 hours of rash onset to achieve clinical benefit in both immunocompetent and immunocompromised patients 1, 2
• There is no information about efficacy of therapy initiated more than 24 hours after onset of signs and symptoms 2

Prophylaxis Misconceptions

• Acyclovir is NOT indicated for prophylactic use in healthy individuals after exposure—vaccination is the method of choice 1
• No studies support prophylactic acyclovir use in immunocompromised persons; VariZIG is recommended instead 1

Salicylate Warning

• Avoid salicylates during and for 6 weeks after varicella due to Reye syndrome risk 1

Monitoring for Complications

• Monitor for bacterial superinfections (particularly invasive group A streptococcal infections), pneumonia, and neurologic complications, which are the leading causes of varicella-related deaths 1

Vaccine-Strain Disease Risk

• Live varicella vaccine given in the week before starting therapy for malignancy was associated with 1 death and has resulted in reactivation of VZV that subsequently became resistant to antiviral drugs 4
• A case report confirmed disseminated vaccine-strain varicella (Oka strain) in a kidney transplant recipient requiring prolonged hospitalization and IV acyclovir 3

Resistance Considerations

• Acyclovir-resistant varicella zoster virus may complicate long-term oral acyclovir administration in patients with AIDS and may be associated with atypical hyperkeratotic papules 7
• For acyclovir-resistant cases, foscarnet 40 mg/kg IV every 8 hours is the treatment of choice 6