Treatment Guideline Chart
Primary herpes simplex virus (HSV) infection is first infection with either herpes simplex virus-1 (HSV-1) or herpes simplex virus-2 (HSV-2) in individuals who do not have antibodies to either HSV-1 or HSV-2.
First episode-non primary infection is infection with either HSV-1 or HSV-2 in individuals who have previously existing antibodies against HSV-1 or HSV-2 respectively.
Recurrent HSV infection results from reactivation of latent virus. It is usually brought about by triggering factors eg UV light, immunosuppression.
Orolabial HSV disease is mostly caused by HSV-1 that occurs most commonly in children <5 years of age. It is transmitted through close contact with individuals who have active viral shedding.
Genital HSV disease is caused by HSV-2 that is the usual cause of herpes genitalis. It typically occurs in adults and transmitted through sexual contact.

Herpes%20simplex%20virus%20infection Treatment

General Treatment Principles of Antivirals

Primary HSV Infection

  • If given within 72 hours of symptom onset, antivirals can be effective in reducing severity and duration of symptoms; however, early treatment of primary infection does not prevent recurrences
  • Choice of agent depends on cost, dosing schedule and patient preference

Recurrent Genital HSV Infection

  • Goals are to treat and prevent symptomatic genital herpes recurrences and preventing transmission to sexual partners by suppressing the virus 
  • Episodic treatment for recurrent genital HSV disease may be given as a single-day patient-initiated treatment or for 5 days
    • Treatment should be given within the 1st 24 hours of symptoms or during prodromal phase
  • Long-term suppressive treatment (prophylaxis) for frequent recurrences of genital HSV disease requires at least 3 months to 1 year of therapy to achieve any efficacy


Symptomatic Therapy

Analgesics/Antipyretics (Oral)

  • Eg Ibuprofen, Paracetamol
  • Symptomatic relief of pain and fever

Anesthetics (Topical)

  • Eg Benzocaine, Dyclonine, viscous Lidocaine
  • Symptomatic relief of pain
  • In theory, may cause sensitization but rarely happens in practice
  • Various topical anesthetics are available. Please see the latest MIMS for specific formulations and prescribing information.


  • Symptomatic relief of pruritus

Oral Preparations

  • Symptomatic relief of ulceration and inflammation in orolabial HSV disease

Zinc Preparations

  • Eg Zinc oxide/glycine cream, Zinc sulfate gel
  • Shorten time of resolution of symptoms

Antivirals - Oral


  • Acyclic purine nucleoside analogue that is a competitive inhibitor of viral DNA polymerase
  • Limits viral replication and stops further spread of the virus to other cells
  • Oral and IV are both effective in treating HSV-1 and HSV-2
    • IV is usually reserved for severe disease or complications where hospitalization is necessary
  • Topical agent has limited efficacy for genital HSV, hence not recommended
  • Bioavailability is poor requiring frequent dosing


  • Famciclovir is a prodrug of Penciclovir
  • Has higher bioavailability than Penciclovir and is rapidly converted to Penciclovir in gastrointestinal tract (GIT), blood and liver
  • Penciclovir has similar mechanism of action as Acyclovir
  • Less effective in suppressing viral shedding


  • L-valine ester prodrug of Aciclovir, rapidly metabolized to Aciclovir by liver and intestine
  • Has better absorption after oral administration than Aciclovir making lower doses or lesser dosing frequency possible
  • Has been shown to decrease risk of transmission


  • Pyrophosphate analogue that is a noncompetitive inhibitor of viral RNA and DNA polymerase
    • Foscarnet is virostatic and activation by thymidine kinase is not required
  • May be used for Aciclovir-resistant mucocutaneous HSV infections in immunocompromised patients

Methisoprinol or Inosiplex

  • Antiviral activity by modifying or stimulating cell-mediated immune process

Antivirals - Topical


  • Same as above 
  • Topical agent has shown limited efficacy


  • May be used for Aciclovir-resistant genital infections


  • Inhibits fusion between the cell plasma membrane and HSV which prevents viral entry into cells and viral replication
  • Decreases healing time of recurrent herpes labialis


  • Same mechanism of action as Aciclovir
  • Decreases healing time of recurrent herpes labialis


  • Derivative of Amantadine with antiviral activity

Non-Pharmacological Therapy

Other Therapies

  • Cool compresses and cool perineal baths/sitz baths may help patients with multiple genital ulcers
  • Intermittent or indwelling bladder catheterization may be considered in patients with urinary retention due to sacral nerve root involvement; referral to a urologist is recommended
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