What is the protocol for Herpes (Herpes Simplex Virus) suppressive therapy?

From the Guidelines

Herpes suppressive therapy should be considered for all patients with frequent or severe recurrences of genital herpes, using daily anti-HSV therapy with oral acyclovir, valacyclovir, or famciclovir, as it is effective in preventing recurrences and reducing viral shedding. The goal of suppressive therapy is to reduce the frequency and severity of herpes outbreaks, as well as decrease viral shedding, which can reduce the risk of transmission to sexual partners. According to the guidelines for prevention and treatment of opportunistic infections in HIV-infected adults and adolescents, suppressive therapy with valacyclovir should be 500 mg twice daily in HIV-infected persons, or twice-daily regimens with acyclovir or famciclovir should be used 1. Daily anti-HSV suppressive therapy in HIV-infected persons also results in a decrease in HIV concentration in plasma and anal and genital secretions, although the clinical benefit or decreased infectiousness is not known 1. Some key points to consider when prescribing suppressive therapy include:

• The most commonly prescribed medications are acyclovir, valacyclovir, and famciclovir
• Treatment can be continued indefinitely, but reassessment after a year may be necessary to determine if continued therapy is necessary
• Side effects are generally mild and may include headache, nausea, or dizziness
• Barrier methods during sexual contact are still advised, as suppressive therapy does not completely eliminate the possibility of spreading the virus
• Adequate hydration should be maintained while taking these medications, and patients with kidney issues may require dosage adjustments. The 1998 guidelines for treatment of sexually transmitted diseases also support the use of daily suppressive therapy, which reduces the frequency of genital herpes recurrences by greater than or equal to 75% among patients who have frequent recurrences 1. However, the most recent and highest quality study, which is the 2009 guidelines for prevention and treatment of opportunistic infections in HIV-infected adults and adolescents, should be prioritized when making a definitive recommendation 1.

From the FDA Drug Label

Suppressive therapy:Two randomized, double-blind, placebo-controlled, 12-month trials were conducted in 934 immunocompetent adults with a history of 6 or more recurrences of genital herpes episodes per year. Comparisons included famciclovir 125 mg three times daily, 250 mg twice daily, 250 mg three times daily, and placebo At 12 months, 60% to 65% of patients were still receiving famciclovir and 25% were receiving placebo treatment. Recurrence rates at 6 and 12 months in patients treated with the 250 mg twice daily dose are shown in Table 8 Table 8: Recurrence Rates at 6 and 12 Months in Adults with Recurrent Genital Herpes on Suppressive Therapy Recurrence Rates at 6 Months Recurrence Rates at 12 Months Famciclovir 250 mg twice daily (n=236) Placebo (n=233) Famciclovir 250 mg twice daily (n=236) Placebo (n=233) Recurrence-free 39% 10% 29% 6% Recurrences † 47% 74% 53% 78% Lost to follow-up ‡ 14% 16% 17% 16%

Herpes Suppressive Therapy: Famciclovir 250 mg twice daily can be used for suppressive therapy in immunocompetent adults with a history of 6 or more recurrences of genital herpes episodes per year. The recurrence rates at 6 and 12 months were lower in patients treated with famciclovir compared to placebo.

• Recurrence-free rates: 39% at 6 months and 29% at 12 months for famciclovir 250 mg twice daily, compared to 10% at 6 months and 6% at 12 months for placebo.
• Recurrence rates: 47% at 6 months and 53% at 12 months for famciclovir 250 mg twice daily, compared to 74% at 6 months and 78% at 12 months for placebo. 2

From the Research

Herpes Suppressive Therapy

• Herpes suppressive therapy is required, especially in patients with frequent and/or severe episodes of genital herpes, as it is associated with major medical and psychosocial morbidities 3.
• A meta-analysis evaluated prophylactic regimens in immunocompetent hosts and proposed four alternatives with similar efficacies: three twice-daily regimens (i.e. acyclovir 400 mg, valaciclovir 250 mg and famciclovir 250 mg) and one once-daily regimen (valaciclovir 500 mg) 3.

Treatment Options

• Valaciclovir 500 mg twice daily maintains the benefits of acyclovir treatment in terms of clinical efficacy and safety, and is an effective option for immunocompromised patients 3.
• A randomized, double-blind study found that all valaciclovir dosages were significantly more effective than placebo at preventing or delaying recurrences, with a dose-response relationship across the once-daily valaciclovir regimens 4.
• Once-daily valacyclovir hydrochloride (500 mg) was found to be highly effective and well tolerated for suppression of recurrent genital herpes in men and women, with 81% of subjects being free of recurrence after the first 3 months of suppressive therapy 5.

Patient Preference

• A randomized study found that 72% of patients preferred suppressive valacyclovir therapy to episodic valacyclovir treatment, with overall treatment satisfaction and quality of life being significantly greater during suppressive therapy 6.
• Suppressive therapy was associated with increased treatment satisfaction, and decreased risk and lower frequency of recurrences, with significantly fewer patients experiencing recurrences during suppressive treatment than with episodic treatment 6.

Comparative Efficacy

• A comparative study found that valacyclovir appeared to be somewhat better than famciclovir for suppression of genital herpes and associated shedding, with valacyclovir recipients having a longer time to first recurrence and lower rates of viral shedding 7.