## Differential Antiviral Susceptibility: HSV-1 vs VZV ### Mechanism of Acyclovir Activation Both HSV-1 and VZV require viral thymidine kinase (TK) for acyclovir activation—this is **not** a distinguishing feature. The key difference lies in **relative drug susceptibility**. **Key Point:** HSV-1 is intrinsically more susceptible to acyclovir than VZV. This is reflected in **lower IC₅₀ values** (concentration required to inhibit 50% of viral replication) for HSV-1. ### Comparative Susceptibility Table | Parameter | HSV-1 | VZV | |-----------|-------|-----| | **IC₅₀ (acyclovir)** | 0.02–0.1 µM | 0.5–1.5 µM | | **Relative susceptibility** | **10–20× more susceptible** | Less susceptible | | **TK requirement** | Yes (viral TK) | Yes (viral TK) | | **Recommended IV dose** | 5 mg/kg q8h | 10–15 mg/kg q8h | | **Oral bioavailability** | ~15–20% | ~15–20% | | **Preferred agent** | Acyclovir | Valacyclovir (higher bioavailability) | **High-Yield:** VZV is **10–20 times less susceptible** to acyclovir than HSV-1. This is why: - HSV-1 responds to lower acyclovir doses (5 mg/kg IV q8h) - VZV requires higher doses (10–15 mg/kg IV q8h) - Oral acyclovir is inadequate for VZV; **valacyclovir** (prodrug with 3–5× better bioavailability) is preferred ### Clinical Implications ```mermaid flowchart TD A[Herpesvirus infection]:::outcome --> B{HSV or VZV?}:::decision B -->|HSV-1/HSV-2| C[High acyclovir susceptibility]:::outcome B -->|VZV| D[Lower acyclovir susceptibility]:::outcome C --> E[Acyclovir 5 mg/kg IV q8h]:::action D --> F[Acyclovir 10-15 mg/kg IV q8h]:::action F --> G{Oral therapy?}:::decision G -->|Yes| H[Valacyclovir preferred]:::action G -->|No| I[IV acyclovir]:::action ``` **Clinical Pearl:** In immunocompromised patients (HIV, transplant), VZV dissemination requires **IV acyclovir** because oral absorption is unreliable. HSV-1 can often be managed with oral acyclovir even in immunosuppressed hosts.
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