Genital herpes is one of the most prevalent sexually transmitted infections in the world today; approximately 45 million adults in the United States are seropositive for herpes simplex virus type 2 (HSV-2).^[1] Although the infection itself is generally not life-threatening, it has a significant morbidity and impact on patients' lives,^[2] and has profound public health implications with respect to the transmission and acquisition of other sexually transmitted infections, including HIV infection.^[3,4]

The ability of HSV-2 to establish latency in sensory nerve ganglia and to undergo periodic reactivation and frequent asymptomatic shedding across mucosal surfaces creates a lifelong potential for transmission to sexual partners and for the possibility of neonatal infection in pregnant women. Further, HSV-2 infection has been demonstrated to significantly increase the transmission and risk of acquisition of HIV.^[3-5] At present, there is no cure for genital herpes infection, but treatment strategies are available to alleviate the acute symptoms of herpes outbreaks, suppress recurrences, reduce asymptomatic shedding, and lower the risk of transmission.

Oral antiviral therapy, until recently, had been prescribed for patients with genital herpes either to alleviate the acute symptoms and signs of an outbreak (initial or episodic treatment) or to prevent HSV reactivation and the subsequent development of recurrent outbreaks (suppressive therapy). The use of chronic, daily antiviral therapy to reduce transmission of genital herpes is a new indication and signifies the most significant development in the management of genital herpes since the introduction of acyclovir.

A Disease of Frequent Viral Shedding

Two factors have contributed greatly to the continuing issue of new transmission events. First, although genital herpes is common, infection is rarely recognized.^[1,6] Second, reactivation of genital infection is the norm with nearly 100% of individuals experiencing reactivation of infection either clinically or asymptomatically.^[7] Thus, the notion of separating genital HSV-2 infection into 2 separate categories of "infection" and "disease" is at best overly simplistic and probably antiquated. The presence of HSV-2 on the genital mucosal surface, whether associated with clinically recognized outbreaks, subclinical outbreaks, or asymptomatic shedding, can and does lead to the transmission of HSV-2.

We now understand that genital herpes infection due to HSV-2 is one of frequent viral shedding. During the first 6 months of infection, shedding can occur during 20% to 40% of days; with longer-term infection, shedding may occur during 5% to 20% of days.^[7] It is the shedding of virus -- and particularly asymptomatic viral shedding -- that is responsible for the transmission of genital herpes. Asymptomatic viral shedding is the presence of virus in the absence of clinical signs or symptoms. Up to 70% of new infections can be attributed to asymptomatic shedding.^[8-10] Asymptomatic shedding occurs in virtually all HSV-2 infected patients, and shedding rates cannot be predicted on the basis of age, sex, or reported history of outbreaks.^[7,11] Shedding of virus can occur from multiple genital sites, and 50% of asymptomatic shedding events occur more than 7 days before or after a clinical outbreak.^[7] And although viral shedding tends to diminish over the course of infection, the rate of decay is measured in years and the potential of transmission persists.