Herpes simplex genitalis antiviral treatment of recurrent genital herpes

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Lakshmi Gopalakrishnan, M.B.B.S.

Overview

Recurrences are usually self-limiting and generally cause minor symptoms. Treatment strategies include supportive therapy, episodic and suppressive anti-viral therapy. The best strategy for managing an individual patient may change over time according to the frequency of recurrence frequency and the symptom severity.

Established HSV-2 Infection

• The majority of patients with symptomatic, first-episode genital HSV-2 infection subsequently experience recurrent episodes of genital lesions; recurrences are less frequent after initial genital HSV-1 infection.

• Intermittent asymptomatic shedding occurs in persons with genital HSV-2 infection, even in those with longstanding or clinically silent infection.

• Antiviral therapy for recurrent genital herpes can be administered either episodically to ameliorate or shorten the duration of lesions or continuously as suppressive therapy to reduce the frequency of recurrences. Majority patients, including those with mild or infrequent recurrent outbreaks, benefit from antiviral therapy.

• On the contrary, suppressive therapy has an additional advantage of decreasing the risk of genital HSV-2 transmission to susceptible partners.

Suppressive Therapy for Recurrent Genital Herpes

• Suppressive therapy reduces the frequency of genital herpes recurrences by 70%-80% in patients who have frequent recurrences (i.e., greater than 6 recurrences per year), and many patients report no symptomatic outbreaks. Treatment also is effective in patients with less frequent recurrences. Safety and efficacy have been documented among patients receiving daily therapy with acyclovir for as long as 6 years and with valacyclovir or famciclovir for 1 year. Quality of life frequently is improved in patients with frequent recurrences who receive suppressive, compared with episodic treatment.

• The frequency of recurrent genital herpes outbreaks diminishes over time in many patients, and the patient's psychological adjustment to the disease may change. Hence, periodically during suppressive treatment (e.g., once a year), the need to discontinue therapy may be discussed.

• Treatment with valacyclovir 500 mg daily decreases the rate of HSV-2 transmission in discordant, heterosexual couples in which the source partner has a history of genital HSV-2 infection. Such couples should be encouraged to consider suppressive antiviral therapy as part of a strategy to prevent transmission, in addition to consistent condom use and avoidance of sexual activity during recurrences. Suppressive antiviral therapy probably reduces transmission when used by persons who have multiple partners and by those who are HSV-2 seropositive without a history of genital herpes.

Chronic Daily Suppression Immunocompetent Patients ▸ Acyclovir 400 mg po bid OR ▸ Famciclovir 250 mg po bid OR ▸ Valacyclovir 1 gm po q24h† Immunocompromised Patients ▸ Acyclovir 400-800 mg po bid or tid OR ▸ Famciclovir 500 mg po bid OR ▸ Valacyclovir 500 mg po bid

†Patients with < 9 recurrences per year could use 500 mg po q24h and then 1 gm po q24h if breakthrough at 500 mg.

500 mg po bid*Valacyclovir 500 mg once a day might be less effective than other valacyclovir or acyclovir dosing regimens in patients who have very frequent recurrences (i.e., more than 10 episodes per year). Several studies have compared valacyclovir or famciclovir with acyclovir. The results of these studies suggest that valacyclovir and famciclovir are comparable to acyclovir in clinical outcome. Ease of administration and cost also are important considerations for prolonged treatment.

HIV Infection

• Immunocompromised patients can have prolonged or severe episodes of genital, perianal, or oral herpes. Lesions caused by HSV are common among HIV-infected patients and might be severe, painful, and atypical.
• HSV shedding is increased in HIV-infected persons. Whereas antiretroviral therapy reduces the severity and frequency of symptomatic genital herpes, frequent subclinical shedding still occurs.
• Clinical manifestations of genital herpes might worsen during immune reconstitution after initiation of antiretroviral therapy.
• Suppressive or episodic therapy with oral antiviral agents is effective in decreasing the clinical manifestations of HSV among HIV-positive persons.
• The extent to which suppressive antiviral therapy will decrease HSV transmission from this population is unknown. HSV type-specific serologies can be offered to HIV-positive persons during their initial evaluation if infection status is unknown, and suppressive antiviral therapy can be considered in those who have HSV-2 infection.

Episodic Therapy for Recurrent Genital Herpes

• Effective episodic treatment of recurrent herpes requires initiation of therapy within 1 day of lesion onset or during the prodrome that precedes some outbreaks. The patient should be provided with a supply of drug or a prescription for the medication with instructions to initiate treatment immediately when symptoms begin.

Subsequent Recurrent HSV Episodes Immunocompetent Patients ▸ Acyclovir 800 mg po tid x 2 days or 400 mg po tid x 5 days OR ▸ Famciclovir 1000 mg bid x 1 day or 125 mg po bid x 5 days OR ▸ Valacyclovir 500 mg po bid x 3 days or 1 gm po once daily x 5 days Immunocompromised Patients-HIV ▸ Acyclovir 400 mg po tid x 5-10 days OR ▸ Famciclovir 500 mg po bid x 5-10 days OR ▸ Valacyclovir 1 gm po bid x 5-10 days