Herpes Simplex Treatment & Management

Updated: May 24, 2021
  • Author: Folusakin O Ayoade, MD; Chief Editor: Michael Stuart Bronze, MD  more...
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Approach Considerations

The antivirals ( oral, intravenous and topical) acyclovir, valacyclovir, famciclovir and pensiclovir are well established treatments for both HSV-1 and HSV-2. They all act by interfering with the viral DNA polymerase and hence, viral genome replication. [27]  


Medical Care

Overall, medical treatment of herpes simplex virus (HSV) infection is centered around specific antiviral treatment. While the same medications are active against HSV-1 and HSV-2, the location of the lesions and the chronicity (primary or reactivation) of the infection dictate the dosage and frequency of medication. Topical treatments do not appear to be as effective as systemic medications. [28]

 Antivirals are effective when taken within 72 hours of lesion appearance in genital herpes. Anticipatory treatment is also recommended in situations where decreasing viral shedding decreases the likelihood of infecting seronegative individuals with the virus. Appropriate wound care is needed, and treatment for secondary bacterial skin infections may be required.

Intravenous (IV) acyclovir therapy should be provided for patients who have severe HSV disease or complications that necessitate hospitalization (e.g., disseminated infection, pneumonitis, or hepatitis) or CNS complications (e.g., meningoencephalitis). 

The initiation of high-dose acyclovir therapy as early as possible in the course of the illness provides the best chance for a patient to survive with minimal neurologic damage. HSV encephalitis requires 21 days of intravenous therapy. [29]

Acyclovir-resistant HSV infections

Acyclovir-resistant HSV infections are often seen in immunocompromised patients (eg, patients with HIV infection). Resistant isolates result in severe, debilitating mucosal disease, and visceral dissemination. The possibility of resistant HSV should be considered whenever lesions persist for more than 1 week without appreciable decrease in size; when they develop an atypical appearance  or when new satellite lesions develop after 3 to 4 days of therapy. [30]  The options for treatment include cidofovir and foscarnet, but both are very nephrotoxic.

Recurrent HSV infections

Options for recurrent HSV infections include no treatment (for infrequent episodes) or episodic treatment with topical agents or oral antiviral agents. Oral antiviral drugs are used for short periods when known precipitating factors might otherwise trigger reactivation of disease. Long-term suppressive therapy, which can be continued for up to one year, is also an option. A modest benefit with lower recurrences has been reported using this method. [31, 32]

The best approach is to determine the frequency and severity of recurrent infections and the patient's preference concerning prophylaxis. Options for long-term suppressive therapy include acyclovir 400 mg orally twice daily or valacyclovir 500 mg orally twice daily for up to a year, with reassessment at the end of therapy.



Consultation with a dermatologist may be beneficial in cases of atypical lesions.

In immunocompromised patients with invasive HSV infection, consultation of specialty associated with the organ system affected should be sought early (eg, pulmonologist for possible HSV pneumonitis) in order to aid in diagnosis. Infectious diseases consultation is reasonable for immunocompromised patients with CNS herpes infection.