A 32-year-old woman presents with severe vesicular lesions on the genitals, fever, and dysuria for 3 days. HSV-2 is confirmed on PCR. She is not pregnant. What is the drug of choice for primary genital herpes simplex infection?

Explanation

## Drug of Choice for Primary Genital HSV Infection **Key Point:** Acyclovir remains the first-line and gold-standard antiviral for primary HSV-2 genital infection, despite newer prodrugs being available. ### Mechanism & Rationale Acyclovir is a nucleoside analogue that: 1. Requires viral thymidine kinase (TK) for activation 2. Inhibits viral DNA polymerase with high selectivity 3. Has the longest track record of safety and efficacy in primary HSV 4. Is available in IV, oral, and topical formulations ### Dosing for Primary Genital HSV **Oral acyclovir:** 400 mg five times daily for 7–10 days (standard regimen) **IV acyclovir:** 5–10 mg/kg IV every 8 hours (reserved for severe disease, immunocompromised, or disseminated infection) ### Why Acyclovir Over Newer Agents? | Feature | Acyclovir | Valacyclovir | Famciclovir | |---------|-----------|--------------|-------------| | **Bioavailability (oral)** | 15–30% | 54% (prodrug of acyclovir) | 77% (prodrug of penciclovir) | | **Dosing frequency** | 5× daily | 2–3× daily | 3× daily | | **Cost** | Lowest | Moderate | Moderate | | **First-line status** | ✓ Gold standard | Alternative | Alternative | | **Renal clearance** | Rapid; adjust in renal failure | Rapid; adjust in renal failure | Less renal dependent | **High-Yield:** Acyclovir is preferred as first-line because it has the most clinical data, is cost-effective, and is equally efficacious to prodrugs when dosed appropriately. Valacyclovir and famciclovir are **alternatives** for patients with poor compliance (fewer daily doses) or those who cannot tolerate acyclovir, not replacements for it. ### Clinical Pearl In non-pregnant women with primary genital HSV, oral acyclovir 400 mg 5× daily for 7–10 days reduces symptom duration by ~1 day and viral shedding by ~50%. Topical acyclovir alone is **insufficient** for systemic disease. ### When to Use IV Acyclovir Instead - Severe disseminated HSV (encephalitis, hepatitis) - Immunocompromised host (CD4 <50) - Inability to tolerate oral medication - Neonatal herpes [cite:Harrison 21e Ch 187]