Approach

The principles of therapy for oral and genital herpes are similar. Therapy is divided into two groups: suppressive and episodic. Suppressive antiviral therapy is taken daily to prevent recurrences and shedding, and episodic therapy is used as needed to treat recurrences. Episodic treatment should be started immediately after clinical diagnosis of active disease, especially during the first clinical episode. If there is a suspicion for first-episode genital herpes, treatment should be started prior to laboratory confirmation.

Oral antivirals

Oral antivirals are the primary treatment. They are indicated for both suppressive and episodic therapy. The goal of daily suppressive treatment is to decrease the number of outbreaks (70% to 80% reduction) and/or reduce the risk of genital herpes transmission (48% reduction).[49][50] The goal of episodic treatment is to shorten the duration of the outbreak. Patients with recurrent genital herpes should be aware that suppressive therapy is an option for management of genital herpes.[51] [ Cochrane Clinical Answers logo ]

The synthetic acyclic purine analogues (or guanine analogues) are highly specific substrates for the viral thymidine kinase and inhibit viral DNA polymerase. All three licensed drugs (valaciclovir, famciclovir, and aciclovir) are effective at shortening the duration and severity of an episode. The choice of drug depends upon patient preference with respect to cost and dosing frequency. Valaciclovir is a prodrug of aciclovir and has greater bioavailability, resulting in less frequent dosing. Famciclovir is the oral form of penciclovir. A dose adjustment may be required for aciclovir, famciclovir, and valaciclovir in patients with renal impairment.

Topical treatment

Treatment of genital herpes with topical antiviral drugs offers minimal clinical benefit, and use is discouraged.[37]​​[52]​​​​

The use of topical therapy for cold sores is not recommended. Oral therapy is preferred for treatment of recurrent herpes simplex labialis over topical antiviral creams. Some patients may prefer the use of antiviral creams due to the lack of required prescription and the ability to avoid oral medication. Antiviral creams have a small but statistically significant effect on the duration of cold sores.

Docosanol cream may reduce healing time of cold sores by 18 hours to 3 days compared with placebo when applied at the start of oral herpes recurrence (tingling sensation or redness).[53][54]

Penciclovir cream shortens the duration of herpes simplex labialis recurrences by 0.7 days when applied every 2 hours while awake compared with placebo.[55] The duration of pain and viral shedding were also significantly decreased with the use of penciclovir cream.

Aciclovir cream decreases herpes simplex labialis outbreaks by 0.5 days.[56]

Suppressive antiviral therapy

Daily suppressive therapy should be offered to patients with frequent or severe recurrences, and may be considered for HIV-uninfected patients with genital herpes who wish to decrease the risk of transmission to sexual partners.[31][50][57]​  Suppressive therapy is of particular benefit to immunosuppressed patients who may have prolonged, severe outbreaks. In immunocompromised patients, suppressive therapy prevents the development of aciclovir-resistant HSV.[58][59] The need for suppressive therapy should be re-evaluated on a yearly basis.​​​

Episodic treatment

Therapy for the first episode of genital herpes is the most critical and should be provided for all patients. Treatment reduces the risk of neurological complications, limits the severity and duration of the disease, and provides symptomatic relief.[60] Valaciclovir, famciclovir, and aciclovir are approved for active disease.[37]

For oral HSV disease, oral aciclovir has been shown to decrease fever, the number of oral lesions, new extraoral lesions, and eating and drinking difficulties in children 1-6 years of age.[61] Treatment may be offered to patients with symptomatic herpetic gingivostomatitis to decrease symptoms and viral shedding. Therapy is most effective when started within 48-72 hours of onset of signs or symptoms. Dosages and duration of therapy differ depending on the drug and the immune status of the host, and by guideline.[37]​​[40]​​​​ Duration of therapy should be extended until all lesions are resolved, particularly in the immunocompromised population. Resistance to these drugs is very rare in immunocompetent persons.[62]

Episodic treatment for recurrent genital HSV should be initiated as quickly as possible when symptoms start. Several regimens are available for treatment of recurrences.

Symptomatic treatment

Prompt initiation of oral antiviral therapy provides the most effective and safe symptomatic treatment available. If additional symptom relief is required, topical lidocaine may be used to manage pain, especially that associated with first-episode genital herpes. Patients should be made aware that lidocaine is associated with allergic reactions.

Analgesics and sitz baths, in which the affected genital area is immersed in lukewarm water for 10-20 minutes as needed for comfort, can also decrease pain associated with severe or prolonged recurrences.[9] Dysuria may also be alleviated by urinating with the genitals submerged in water.

Disseminated or CNS disease

Suspected or confirmed disseminated HSV infection, including oesophagitis, hepatitis, pneumonitis, or central nervous system (CNS) disease (encephalitis or meningitis), should be treated with high-dose intravenous aciclovir. Length of therapy depends on severity and site of disease: in most cases therapy should be continued for at least 21 days. Patients with CNS or disseminated disease should be managed with the assistance of an infectious disease consultant. See Encephalitis.

Management of genital herpes in pregnancy

Suppressive therapy should be offered to pregnant women with a first-episode outbreak of genital herpes infection during early pregnancy, or women with a prior clinical history of HSV-2. Prophylaxis should start at 36 weeks' estimated gestational age until delivery to reduce the risk of HSV shedding, genital herpes recurrence at delivery, and the need for caesarean delivery for genital herpes.[37]​ There is insufficient evidence to determine whether this approach reduces the incidence of neonatal herpes.

For patients with a primary or non-primary first-episode genital HSV infection, antiviral treatment should be administered at the time of the initial outbreak to reduce symptom duration, severity, and viral shedding. Treatment may be extended if healing is incomplete after 10 days. For patients with recurrent genital HSV episodes during pregnancy, antiviral therapy should be initiated within 48-72 hours of symptom onset, or earlier if possible, at the onset of prodrome.

In cases where primary or non-primary first-episode genital HSV infection occurs during the third trimester of pregnancy, caesarean delivery may be offered due to the possibility of prolonged viral shedding.[48][63][64][65]​​​​​

Treatment failure

Treatment failure is rare in the immunocompetent population, and when it occurs, should lead to re-evaluation of the diagnosis. In immunosuppressed persons, impaired immune clearance is an important predisposing factor for severe infection and development of antiviral resistance.[66] Treatment failure due to resistance should be considered whenever lesions persist in size for more than one week, when they develop an atypical appearance (e.g., deep ulceration, hyperkeratotic or verrucous features, or involvement in atypical areas, such as the sacrum); or when new satellite lesions develop after three to four days of therapy. Laboratory documentation of aciclovir resistance with viral culture is recommended and the patient should be managed in consultation with an infectious disease consultant.[37] HSV isolates that are resistant to aciclovir are also resistant to valaciclovir, and the majority are resistant to famciclovir.[37] In this scenario, a trial of foscarnet may be appropriate.[37]​​[67]​​​​​​ However, because of toxicities associated with foscarnet, this should be reserved for severe disease refractory to intravenous or high-dose oral aciclovir or valaciclovir. Although aciclovir-resistant HSV mutants are usually less fit and unlikely to become latent, repeat resistance testing is also recommended with recurrent episodes.

A dose adjustment is required for foscarnet in patients with renal impairment.

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