Morphology: Enveloped, double-stranded DNA virus. Family Herpesviridae, subfamily Alphaherpesvirinae. Establishes latency in trigeminal ganglia after primary orolabial infection; periodic reactivation.
Typical drugs
- #1Acyclovir— First-line for severe / encephalitis / disseminated disease (IV). PO outpatient prodrugs (valacyclovir / famciclovir) preferred for adherence but not yet seeded.
Empiric therapy when resistant
Acyclovir-resistant HSV is rare in immunocompetent patients. In transplant / advanced HIV with non-healing lesions despite ACV → switch to foscarnet 40–60 mg/kg IV q8h (renally dosed).
Resistance mechanisms
altered-target
Thymidine kinase (TK) mutations → acyclovir resistance
Example: Mostly in immunocompromised hosts with chronic suppressive use. Salvage: foscarnet (PFA-binds DNA polymerase, TK-independent) or cidofovir.
Resistance notes
Acyclovir resistance in <1% of immunocompetent; rises to ~5–10% in HSCT recipients on chronic suppressive therapy.
Pearls
HSV-1 classically orolabial, HSV-2 genital — but cross-presentation is increasingly common. HSV encephalitis = boards classic: temporal lobe focal neuro signs + RBC-tinged CSF + temporal lobe enhancement on MRI → start ACV 10 mg/kg IV q8h empirically while CSF PCR pends, × 14–21 days. Mucocutaneous HSV in immunocompromised — disseminated, severe, may need IV ACV + chronic suppression. Neonatal HSV — devastating; deliver via C-section if active maternal lesions, IV ACV 20 mg/kg q8h × 21 days for any neonate with mucocutaneous, CNS, or disseminated disease. Bell's palsy + zoster sine herpete + erythema multiforme all can be HSV-driven.