Short-course therapy for recurrent genital herpes and herpes labialis
Entering an era of greater convenience, better treatment adherence, and reduced cost.
Herpes simplex virus (HSV) type 1 (HSV-1) or type 2 (HSV-2) results in periodic, recurrent outbreaks of skin lesions after first infection. Herpes labialis (fever blisters or cold sores) is usually caused by HSV-1, while genital herpes is usually caused by HSV-2.4 HSV-2 lesions of the lips have been reported, and the incidence of genital herpes caused by HSV-1 is on the rise in the developed world, likely because of increased oral-genital sexual behavior.5,6 Patients with HSV-1 genital herpes typically have fewer recurrences than those with HSV-2 genital infection.7
The prevalence of HSV-1 and HSV-2 infection varies according to age, geography, gender, and population subgroup, such as people who exhibit high-risk sexual behavior.8 approximately 45% of americans are infected with HSV-1 by adolescence,8 and approximately 22% of all american adults are infected with HSV-2.9 The global prevalence of HSV is even greater: as many as 60% to 90% of older adults worldwide are seropositive for HSV-1, and as many as 30% are seropositive for HSV-2. HSV-2 seropositivity is more prevalent among women than men.8 overall, the burden of recurrent genital herpes outbreaks can have a profound, negative impact on patient quality of life.10,11 The psychological impact of recurrent herpes labialis has not been thoroughly investigated, but an undefined burden is thought to exist, particularly in young patients with frequent or severe recurrences.12
The primary endpoint was time to lesion healing (defined as the number of days from initiation of therapy to lesion reepithelialization). Secondary endpoints were pain duration, episode duration (defined as time from initiation of therapy to resolution of all symptoms) and percentage of patients with aborted lesions.
The 3-day valacyclovir treatment exhibited similar time to lesion healing, length of episode, and percentage of patients with aborted lesions as the 5-day treatment (TABLE 1), suggesting equal efficacy. Duration of pain was also similar (data not shown). Adverse events were similar for both treatment groups, with the most common being headache (10%), nausea (4%), and diarrhea (4%, 5-day treatment vs 2%, 3-day treatment).
Placebo-controlled trial of 2-day acyclovir therapy. Wald and coworkers examined the effect of a shorter treatment regimen of acyclovir (2 days) on recurrent genital herpes.28 Eighty-four immunocompetent HSV-2–infected patients with a history of ≥3 recurrences in the previous 12 months were randomized to receive either 2 days of 800 mg 3 times daily acyclovir or matching placebo. Patients were asked to take their medication no later than 12 hours after the first sign or symptom of an episode.
Efficacy endpoints were time to lesion healing, episode duration, and percentage of patients with aborted lesions. Short-course acyclovir therapy was shown to decrease time to healing (P=.001) and episode duration (P<.001) by 2 days compared with placebo (TABLE 1). Short-course acyclovir therapy also increased the percentage of patients with aborted lesions compared with placebo (27% vs 11%; P=.029 (TABLE 1). Adverse events were not recorded in this analysis.
Placebo-controlled trial of single-day famciclovir therapy. Aoki and colleagues29 performed a randomized, double-blind, patient-initiated, placebo-controlled trial to assess the efficacy and safety of patient-initiated, single-day famciclovir 1000 mg twice daily in immunocompetent adults with recurrent genital herpes. The 329 patients in the study were instructed to self-initiate therapy within 6 hours of the onset of prodromal symptoms or genital herpes lesions, and were asked to return to the clinic no later than 24 hours after initiation of therapy. Patients were followed until their lesions healed or for up to 14 days.
The primary endpoint was time to lesion healing of nonaborted lesions. Secondary endpoints were time to healing of all lesions (aborted and nonaborted), time to resolution of pain and other symptoms, and the percentage of patients who did not progress to a full outbreak.
Single-day treatment with famciclovir shortened the time to healing of nonaborted genital herpes lesions by approximately 2 days (P<.001), and the time to healing of all lesions by 1.5 days (P<.001) compared with placebo, and increased the percentage of patients who did not progress to a full outbreak (23% vs 13%;P=.003) (TABLE 1). Famciclovir also reduced the time to resolution of all symptoms by approximately 2 days (P<.001) (data not shown).
Adverse events were mild to moderate; the most common in the famciclovir and placebo groups, respectively, were headache (13.5% vs 5.4%), nausea (2.5% vs 3.6%), and diarrhea (4.9% vs 1.2%).
