Length of genital herpes outbreaks decreases with shortened treatment cycle

Single-day treatment with famciclovir reduced lesions by two days compared with placebo.

Issue: February 2006

WASHINGTON — A single day of treatment with the antiviral famciclovir (Famvir, Novartis) stopped the progression to a full outbreak, or shortened the duration of an outbreak, in people with recurrent genital herpes.

Fred Y. Aoki, MD, professor of medicine at the University of Manitoba in Winnipeg, Canada, said that the current standard of care for recurrent genital herpes is three or five days of oral antiviral therapy, but recent observations show shorter regimens help without a loss of efficacy.

“The concentration of HSV in herpes labialis lesions only increases over the first 24 hours and after that it spontaneously declines,” Aoki said at the 45th Interscience Conference on Antimicrobial Agents and Chemotherapy. “Extrapolating to genital herpes lesions, one would expect that a drug that’s going to work to abbreviate the cause of herpes simplex virus [HSV] infection would have to be applied within the first 24 hours. We, therefore, hypothesized that a single–day treatment would be efficacious as well as be convenient for the treatment of recurrent genital herpes infection.”

Single-day famciclovir

The researchers evaluated patient–initiated episodic therapy of recurrent genital herpes with famciclovir compared with placebo. Researchers instructed study participants to initiate therapy when they detected the initial signs of a herpes outbreak. Then, participants returned within 24 hours of initiating therapy and on days 2 and 3. People with lesions beyond day 3 returned to the clinic on days 4 and 5 and every other day until all the lesions healed, or on day 14.

Fred Y. Aoki

Aoki and colleagues defined healing as loss of all crusts and normalization of the skin. They defined aborted lesions as herpetic lesions not progressing beyond papule stage.

In the multicenter, double–blind, placebo–controlled trial, researchers administered 1,000 mg of famciclovir or placebo twice daily to an immunocompetent study population aged 18 or older with HSV–2 infection. Participants experienced recurrent genital herpes, classified as four or more episodes in the preceding 12 months. Median age of famciclovir and placebo participants was 41 and 42, respectively. Most participants in both treatment arms were women: treatment group (n=111) and placebo group (n=122).

The results comparing famciclovir (n=163) with placebo (n=166) showed that when patients with recurrent genital herpes initiated therapy within the first six hours of an outbreak, famciclovir reduced the time to healing of nonaborted lesions by two days (median time 4.3 days vs. 6.1; P = .0001). The proportion of patients with aborted lesions was significantly larger in the famciclovir group compared with the placebo group (23.3% vs. 12.7%; P = .003).

Source: Fred Y. Aoki, MD

Famciclovir also reduced the duration of all studied symptoms, including the itching, pain, burning, tingling and tenderness in patients with lesions vs. those taking placebo (median time 3.3 vs. 5.4 days; P< .0001). Adverse event frequency and severity in the famciclovir group was infrequent overall, of mild–to–moderate severity and similar to those in the placebo group. Most common adverse events reported by the treatment group were headache (14%) and diarrhea (5%), compared with 5% and 1%, respectively, in the placebo–treated group.

“So, we concluded then that single-day famciclovir, 1,000 mg twice a day, started within six hours of onset of a recurrent genital herpes outbreak, is efficacious, well tolerated and, we think, convenient, and [it] has potential to improve the overall management of recurrent genital herpes,” Aoki said.

Arm the patient against herpes

Genital herpes is one of the most common sexually transmitted diseases in the United States and infects approximately one in five, or about 50 million, Americans. Nearly 90% of people affected with genital herpes may not know they are infected.

There is no cure for genital herpes. Current treatment regimens for episodic genital herpes are acyclovir (200 mg five times daily for five days or 800 mg three times daily for two days), famciclovir (125 mg twice daily for five days) and valacyclovir (Valtrex, GlaxoSmithKline; 500 mg twice daily for three days).

“The take home message is that doctors may need to spend an extra few minutes to teach their patients how to both recognize the earliest symptoms of recurrent genital herpes and to provide prescriptions that enable patients to have the famciclovir close at hand [and] to start the medicine as quickly as possible after symptoms begin,” Aoki told Infectious Disease News. “The importance of early initiation of therapy can’t be overemphasized.” – by Judith Rusk and Tara Grassia

Dr. Aoki is a paid consultant for GlaxoSmithKline and Novartis.

For more information:

Aoki FY, Tyring S, Diaz-Mitoma F, et al. Patient-initiated high-dose oral famciclovir for one day shortens the duration of recurrent genital herpes lesions. Presentation V-1389. Presented at: 45th Interscience Conference on Antimicrobial Agents and Chemotherapy; Dec. 16-19, 2005; Washington.

Aoki FY, Tyring S, Diaz-Mitoma F, et al. Single-day, patient-initiated famciclovir therapy for recurrent genital herpes: a randomized, double-blind, placebo-controlled trial. Clin Infect Dis. 2006;42:8-13.

Leone PA, Trottier S, Miller JM. Valacyclovir for episodic treatment of genital herpes: a shorter 3-day treatment course compared with 5-day treatment. Clin Infect Dis. 2002;34:958-962.

Wald A, Carrell D, Remington M, et al. Two-day regimen of acyclovir for treatment of recurrent genital herpes simplex virus type 2 infection. Clin Infect Dis. 2002;34:944-948.