(682) Antivirals for Herpesviridae: Nucleoside Analogues

Nucleoside analogues are a class of antiviral drugs targeting Herpes Simplex Virus (HSV) and Varicella Zoster Virus (VZV) infections.

Acyclovir

• Indications: First-choice for HSV and VZV infections.

• Resistance: Common, requires alternative agents; dose increase is ineffective.

• Forms: Oral (PO), Intravenous (IV), Topical.

  • PO: Can cause GI upset, vertigo. Used in pregnancy for near-term herpes simplex outbreaks.

  • IV: Risks include phlebitis, reversible nephrotoxicity (requires hydration, urinary output monitoring, dose adjustment for renal impairment), and rare neurotoxicity (agitation, tremors, delirium, hallucinations, increased risk with renal impairment). Infuse slowly over at least $1$ hour.

  • Topical: Applied for recurrent herpes labialis ($5 imes 10^{-2}$ (5%) cream, $5$ times/day for $4$ days). Causes local burning/stinging; no systemic effects.

Valacyclovir

• Prodrug of acyclovir.

• Indications: Herpes Zoster, Herpes Simplex (genital, labialis), Varicella (preventative).

• Immunocompetence: Requires immunocompetent patients; contraindicated in immunocompromised due to risks of Thrombotic Thrombocytopenic Purpura (TTP) and Hemolytic Uremic Syndrome (HUS).

• Other: Approved for children; can be taken without meals; renal function assessment is essential pre-administration.

Famciclovir

• Prodrug.

• Indications: Acute Herpes Zoster, Genital Herpes Infection.

• Benefits: Equivalent to acyclovir.

• Adverse Effects: Minimal.

Herpes Simplex Virus (HSV)

• Forms: Herpes Labialis (cold sores, primarily HSV-1); Herpes Genitalis (HSV-1 or HSV-2).

Herpes Labialis (Cold Sores)

• Causative Agent: Primarily HSV-1; transmitted via infected saliva.

• Pathology: Dormant in sensory nerve ganglia; reactivated by stress, infection, sun. Symptoms: burning/tingling, painful blisters, ulcerations.

• Resolution: Spontaneous within $3$ weeks; antivirals accelerate healing.

• Topical Treatments (inhibit viral DNA replication unless stated):

  • Acyclovir ($5 imes 10^{-2}$ (5%) cream): Recurrent herpes labialis, applied $5$ times/day for $4$ days. Local burning/stinging, no systemic effects.

  • Penciclovir ($1 imes 10^{-2}$ (1%) cream): Applied every $2$ hours for $4$ days; modest benefit (reduces healing by $0.5$ to $5$ days). Mild local erythema.

  • Docosanol ($1 imes 10^{-1}$ (10%) cream): Blocks viral entry; applied at first sign, $5$ times/day for $4$ days. Modest benefit, few adverse effects, unlikely resistance.

Herpes Genitalis

• Causative Agent: Most commonly HSV-2.

• Presentation: Blisters, vesicles, ulcer-like sores, dysuria, watery discharge, systemic symptoms (fever, headache, myalgia, swollen lymph nodes). Can be asymptomatic/mild.

• Course: Lifelong with recurrences; episodes may shorten/lessen over time. Spontaneous resolution, but no cure.

• Patient Education: Abstain from sexual activity during breakouts due to increased viral shedding.

• Treatment Goals: Decrease symptoms, shorten duration of pain and viral shedding; drugs do not eliminate the virus.

• Treatment Strategies: Continuous daily suppression or episodic treatment.

• First Episode Treatment: Oral acyclovir, famciclovir, or valacyclovir for $7-10$ days. Severe episodes require Acyclovir IV (every $8$ hours for $2-7$ days), then PO.

• Recurrent Episodes: Acyclovir, famciclovir, valacyclovir are options for daily suppressive therapy.

Varicella Zoster Virus (VZV)

Varicella (Chickenpox)

• Contagious: Highly contagious, mainly in children (vaccination greatly reduces transmission).

• Presentation: Maculopapular rash (face, scalp, trunk), fever, malaise, loss of appetite.

• Complications (untreated): Pediatric: bacterial superinfection, Reye syndrome (rare), encephalitis (rare). Adults: pneumonia, severe symptoms, hospitalization, death.

• Treatment (active infection): Immunocompetent: Acyclovir PO for $5$ days. Immunocompromised: Acyclovir IV every $8$ hours for $7$ days.

• Prevention: Vaccination (MMR, Varicella Virus Vaccine - Varivax, both live, subcutaneous). Contraindications: pregnancy, leukemia/lymphoma, neomycin/gelatin allergy, immunocompromised status. Avoid aspirin/salicylates for $6$ weeks post-vaccine in pediatric patients due to Reye syndrome risk. Schedule: $12-15$ months (1st dose), $4-6$ years (2nd dose); Children $13+$ (no prior exposure): two doses at least $28$ days apart.

Herpes Zoster (Shingles)

• Causative Agent: Reactivation of dormant VZV (from childhood chickenpox).

• Presentation: Unilateral red/vesicular rash following linear dermatome pattern (head/torso); persists for weeks/months. Pain, paresthesias, sensitive skin, pruritus.

• Complications (untreated): Neuralgia, blindness.

• Treatment: Immunocompetent: Acyclovir PO ($7-10$ days), Valacyclovir PO ($7$ days), or Famciclovir PO ($7$ days). Immunocompromised: Acyclovir IV every $8$ hours for $7$ days. Acyclovir resistance requires Foscarnet IV. Adjunctive therapy (antidepressants/anticonvulsants) for nerve pain.

• Prevention: Vaccination (Zostavax recombinant vaccine, or live vaccine) for patients aged $15$ or $16+$ years respectively.