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General Treatment Principles of Antivirals
Antiviral treatment can decrease symptom duration and severity but cannot cure the infection.
Primary Herpes Simplex Virus 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. Notably, the choice of agent depends on cost, dosing schedule and patient preference.
Recurrent Orolabial Herpes Simplex Virus Infection
Antivirals may not be necessary for mild to moderate symptoms but may be used for more severe recurrences. Episodic treatment must be initiated as soon as possible for it to be effective given the rapid development of vesicles.
Recurrent Genital Herpes Simplex Virus Infection
Goals are to treat and prevent symptomatic genital herpes recurrences and prevent transmission to sexual partners by suppressing the virus. The episodic treatment for recurrent genital herpes simplex virus disease may be given as a single-day patient-initiated treatment or for 5 days. Treatment should be given within the first 24 hours of symptoms or during prodromal phase. Long-term suppressive treatment (prophylaxis) for frequent recurrences of genital herpes simplex virus disease requires at least 3 months to 1 year of therapy to achieve any efficacy.
Pharmacological therapy
Symptomatic Therapy
Analgesics/Antipyretics (Oral)
Example drugs: Ibuprofen, Paracetamol
Analgesics or antipyretics are used for symptomatic relief of pain and
fever.
Anesthetics (Topical)1
Example drugs: Benzocaine, Dyclonine, viscous Lidocaine
Topical anesthetics are used for symptomatic relief of pain. It must be
noted that they may cause sensitization in theory but rarely happens in
practice.
1Various topical anesthetics are available. Please see
the latest MIMS for specific formulations and prescribing information.
Antipruritics
Antipruritics are used for the relief of pruritus.
Oral Preparations
Oral preparations are used for symptomatic relief of ulceration and
inflammation in orolabial herpes simplex virus disease.
Zinc Preparations
Zinc preparations include zinc oxide, glycine cream, and Zinc sulfate
gel. They are used to shorten the time of resolution of symptoms.
Antivirals – Oral
Herpes Simplex Virus Infection_Management 1Aciclovir
Aciclovir is an acyclic purine nucleoside analogue that is a competitive inhibitor of viral DNA polymerase. It 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, but IV is usually reserved for severe disease or complications where hospitalization is necessary. It must be noted that its bioavailability is poor, requiring frequent dosing.
Famciclovir
Famciclovir is a prodrug of Penciclovir. It has a similar mechanism of action as Aciclovir but is dosed less frequently. It is also less effective in suppressing viral shedding.
Valaciclovir
Valaciclovir, an L-valine ester prodrug of Aciclovir, is rapidly metabolized to Aciclovir by the liver and intestine. It has better absorption after oral administration than Aciclovir making less dosing frequency possible. It has been shown to decrease the risk of transmission.
Foscarnet
Foscarnet is a pyrophosphate analogue that is a non-competitive inhibitor of viral RNA and DNA polymerase. Foscarnet is virostatic and activation by thymidine kinase is not required. Although resistance to Aciclovir and its derivatives is rare, drugs such as Foscarnet and Cidofovir may be used for Aciclovir-resistant mucocutaneous herpes simplex virus infections. However, the use of Cidofovir is limited due to adverse effects.
Methisoprinol or Inosiplex
The antiviral activity of Methisoprinol or Inosiplex is by modifying or stimulating cell-mediated immune process.
Antivirals – Topical
Herpes Simplex Virus Infection_Management 2Aciclovir
Aciclovir as a topical agent has shown limited efficacy.
Cidofovir
Topical Cidofovir may be used for Aciclovir-resistant genital infections.
Docosanol
Docosanol inhibits fusion between the cell plasma membrane and herpes simplex virus which prevents viral entry into cells and viral replication. It decreases healing time of recurrent herpes labialis.
Penciclovir
Penciclovir has the same mechanism of action as Aciclovir. Penciclovir decreases the healing time of recurrent herpes labialis.
Tromantadine
Tromantadine is a derivative of Amantadine with antiviral activity.
Management Strategies for Recurrent Genital Herpes
Supportive Treatment Alone
Recurrent infections are generally self-limiting and less severe with a shorter duration of symptoms; supportive treatment alone may be effective to control symptoms.
Episodic Antiviral Treatment
In episodic antiviral treatment, the therapy is patient-initiated and needs to be pre-prescribed. Antiviral therapy is started at the first sign of prodromal symptoms (eg tingling, paresthesia, pruritus) which can occur prior to the appearance of distinct lesions. It is best for herpes simplex virus-infected patients who have mild symptoms and infrequent recurrences. It reduces the duration of viral shedding and symptoms by 1 to 2 days.
Suppressive Antiviral Therapy
Suppressive antiviral therapy is recommended in patients with frequent recurrent genital herpes (≥6 episodes per year), severe or painful prodromes, pregnant patients with herpetic lesions in the last trimester, patients with psychological problems due to the infection, immunocompromised patients, and in immunocompetent patients who want to reduce transmission risk to an uninfected sexual partner regardless of symptom severity. It is used to decrease frequency of recurrences, chance of transmission and provide relief of symptoms. Antivirals suppress symptomatic and asymptomatic viral shedding, reducing clinical outbreaks and viral shedding by 80% and 95% respectively. The full suppressive effect is usually obtained when in treatment for 5 days. Outbreaks during therapy should warrant investigation for poor compliance, need for dose adjustments, treatment resistance or incorrect diagnosis. Annual evaluation and cessation of therapy after 1 year is required to assess frequency of recurrences. The period of assessment includes 2 recurrences to view both severity and frequency. It is safe and advisable to restart suppressive treatment in patients who continue to have significant infections. Although suppressive treatment may incur higher costs and inconvenience.
Nonpharmacological
Parent/Patient
Counseling
It
is important to reduce the patient's anxiety and help them to cope with the
infection by educating them on the natural history of the disease, recurrent
episodes, risk for HIV, diagnostic testing, antiviral treatments, sexual
relationships, and perinatal transmission.
Discuss
treatment options:
- Episodic treatment versus suppressive treatment
- If the patient has ≥6 episodes per year, consider suppressive treatment
- Suppressive treatment may incur higher costs and inconvenience
- Increase fluid intake to dilute urine
Other
Therapies
It
must be noted that drinking cold drinks or sucking on popsicles can alleviate
pain from oral lesions. Cool compress and cool perineal baths or sitz baths may
help patients with multiple genital ulcers. Sitting in a warm bath without soap
for 20 minutes may also help decrease symptoms of genital herpes. 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.
Phòng ngừa
Educate
patients on how to prevent transmission of genital herpes by:
- Abstaining from sexual contact during lesion recurrences or prodromes
- Limiting the number of sexual partners
- Informing current and former sexual partner(s) from preceding 60 days prior to diagnosis to seek evaluation and treatment
- Understanding that asymptomatic viral shedding may cause transmission
- Asymptomatic viral shedding is more likely to occur with HSV-2 infection, in the first year following an infection, or if recurrences are symptomatic; however shedding decreases with time
- Using a condom may help protect against transmission (not foolproof)
- Correct use of condoms reduces the risk of genital herpes because the infected area or site of potential exposure is covered
Male
circumcision can provide lifelong partial protection against HSV-2 and other
STIs. Prevention of oral herpes transmission involves avoidance of oral contact
with other individuals, including oral sex and sharing of objects that come in
contact with the infected person’s saliva. Patients should be advised to avoid
contact with immunocompromised persons or neonates while lesions are present. Athletes
with cutaneous HSV-1 infection (herpes gladiatorum) should not participate in
contact sports until lesions are in the dry crust stage. Recurrences of herpes
labialis can be prevented by avoiding triggers (eg UV light exposure) and
sunscreen use.
Herpes Simplex Virus Infection_Management 3