Why does the chickenpox virus create a risk of herpes zoster during its latent period, even if the acute infection was treated with aciclovir (antiviral medication)?

Why Varicella-Zoster Virus Remains a Risk for Herpes Zoster Despite Aciclovir Treatment of Acute Chickenpox

Aciclovir treatment during acute chickenpox infection does not prevent future herpes zoster because the drug does not eradicate latent virus from neuronal ganglia—it only controls active viral replication during the acute phase. 1, 2

Mechanism of Viral Latency and Aciclovir's Limitations

Why Latency Persists Despite Treatment

• After primary varicella infection, VZV establishes latency in neuronal ganglia regardless of whether acute infection is treated with aciclovir 1
• The virus migrates to dorsal root ganglia during the acute infection phase, where it remains dormant in a non-replicating state 1
• Aciclovir neither eradicates latent virus nor affects the subsequent risk, frequency, or severity of reactivation after the drug is discontinued 1

How Aciclovir Works (and Why It Doesn't Eliminate Latent Virus)

• Aciclovir requires activation by viral thymidine kinase (TK) to become effective, which only occurs during active viral replication 2
• During latency, VZV exists in a dormant state with minimal to no viral replication, meaning viral TK is not being produced and aciclovir cannot be activated 2
• The drug works through competitive inhibition of viral DNA polymerase, incorporation into viral DNA chains, and inactivation of viral DNA polymerase—all mechanisms that require active viral replication 2

Clinical Implications for Herpes Zoster Risk

Lifetime Risk Remains Unchanged

• Approximately 20-30% of people will develop herpes zoster over their lifetime, with incidence increasing markedly after age 50 1
• This risk applies equally to those who received aciclovir during acute chickenpox and those who did not 1
• The increased risk with aging is associated with relative loss of cell-mediated immunity to VZV that occurs naturally 1

Special Populations at Higher Risk

• Immunocompromised patients have significantly elevated risk of VZV reactivation regardless of prior aciclovir treatment 1
• In allogeneic hematopoietic cell transplant recipients with a history of VZV infection, approximately 30% experience reactivation without antiviral prophylaxis 1
• HIV-infected adults have a greater than 15-fold higher incidence of herpes zoster compared to age-matched controls 1

Prevention Strategies (Since Treatment Doesn't Prevent Latency)

Prophylactic Approaches for High-Risk Patients

• Long-term prophylaxis with aciclovir or valacyclovir (not acute treatment) can prevent VZV reactivation during periods of immunosuppression 1
• For allogeneic transplant recipients, prophylaxis for at least 1 year post-transplant significantly reduces VZV disease (9% vs 25% without prophylaxis) 1
• Recipients of blood and bone marrow transplants routinely receive aciclovir 800 mg twice daily or valacyclovir 500 mg twice daily during the first year after transplantation 1

Vaccination as the Only True Prevention

• Zostavax vaccine boosts VZV-specific cell-mediated immunity in adults over 50 years, reducing the burden of herpes zoster and postherpetic neuralgia 3
• Varivax (live-attenuated vaccine) prevents primary varicella infection, which would eliminate the source of future latent virus 3

Common Pitfalls to Avoid

• Do not assume that treating acute chickenpox with aciclovir provides any protection against future herpes zoster—counsel patients that their lifetime risk remains unchanged 1
• Do not confuse acute treatment with suppressive prophylaxis—only continuous prophylactic therapy during immunosuppression prevents reactivation 1
• Recognize that even with suppressive therapy, aciclovir does not eliminate latent virus; it only prevents reactivation during the period of administration 1
• In immunocompromised patients, consider long-term prophylaxis rather than relying on acute treatment history 1