New evidence shows drug reduced transmission of HSV-2

August 2003

Herpesviridae is a family of DNA-viruses containing approximately 100 herpesviruses — nine of which can cause infections in humans.

Two of these, herpes simplex virus type 1 and type 2 (HSV-1 and HSV-2), affect many people and can cause infections ranging from mucocutaneous lesions to life threatening illness.

Herpes simplex virus-2 is primarily responsible for causing herpes genitalis or genital herpes. However, HSV-1 is responsible for herpes genitalis in approximately 33% of cases. Genital herpes is one of the most common sexually transmitted diseases (STDs) with a 60% risk of acquiring HSV-2 after a sexual encounter with an infected partner. Most patients develop genital lesions within three days to two weeks after the initial encounter with HSV-2.

Virus transmission

Herpes simplex viruses are transmitted through bodily secretions such as saliva, cervical fluid, semen and vesicle fluid from herpetic lesions. Transfer of the virus occurs upon contact with a mucosal surface, such as the oropharynx, genital and anal areas, ocular areas, respiratory tract, blood or broken skin. Initial replication of the virus and infection occur at the site of transmission. The virus then travels to the dorsal root ganglia and becomes latent.

Unfortunately, HSV is a lifelong infection that is incurable. Many patients suffer from recurrent outbreaks provoked by various environmental and patient specific factors. A prodromal syndrome that may include localized tingling and/or pain, burning, lymphadenopathy, fever, malaise or tenderness, typically precedes the formation of lesions.

Viral replication and shedding occur during active infection. It is during this time that the virus can be spread to an uninfected person. During the primary genital herpes infection, viral replication and shedding can occur for as long as three weeks. However, viral shedding persists for approximately three days with recurrent infections.

Unfortunately, many patients may shed virus without clinical symptoms of infection or presence of lesions. Asymptomatic viral shedding can occur during HSV-1 and HSV-2 infections. Many patients are seropositive for HSV, yet have never suffered from herpetic lesions and/or clinical symptoms. Epidemiologic studies have identified that most cases are transmitted from a person without any history of herpetic lesions or clinical symptoms of genital herpes. Asymptomatic viral shedding could be the predominant source of transmission, specifically in genital herpes, and is a major concern in regards to progression of HSV.

Various antivirals have been used in the treatment of HSV-2 including, acyclovir, valacyclovir (Valtrex, GlaxoSmithKline) and famciclovir (Famvir, Novartis). These medications are prescribed to treat primary and recurrent infections. Additionally, these antivirals can be used chronically as suppressive therapy. Acyclovir, valacyclovir and famciclovir have demonstrated equal efficacy in treating herpes genitalis when taken orally. Acyclovir must be dosed frequently secondary to its low oral bioavailability and short half-life. Valacyclovir and famciclovir have a higher oral bioavailability and are dosed less frequently, improving compliance.

Proven effective

Antivirals have been proven effective in decreasing asymptomatic shedding of HSV-2. However, the impact of suppressive therapy has not been evaluated regarding the transmission of HSV-2, until recently. Data were presented at the 42nd Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) meeting regarding the reduction in transmission of genital herpes with suppressive valacyclovir therapy.

Corey et al conducted a placebo-controlled trial involving 1,484 heterosexual, monogamous couples. One of the partners in each couple was seropositive for HSV-2 and one was seronegative. Couples were randomized to valacyclovir 500 mg orally once a day or placebo and followed for eight months.

The couples were provided with safe-sex counseling, including the use of condoms, and encouraged to practice safe-sex. At monthly intervals, the seronegative partner was assessed for serologic conversion as well as for clinical signs of genital herpes.

The valacyclovir treated couples had a significant reduction in HSV-2 transmission. In the valacyclovir group, four (0.5%) patients developed genital herpes compared with 17 (2.3%) in the placebo group (77% reduction in transmission). In addition, there was a reduction in asymptomatic transmission of the virus with 14 (1.9%) patients in the valacyclovir group developing genital herpes compared to 28 (3.8%) in the placebo group (50% reduction in asymptomatic transmission).

While the outcome is promising, the trial is limited by the population studied. These results should not be extrapolated to homosexual males or people with multiple sexual partners. In addition, couples in the study were provided with condoms and safe-sex counseling. Therefore, if suppressive therapy is used in clinical practice, specifically for reduction of transmission of HSV-2, programs need to be established to provide patients with similar safe-sex counseling. Although valacyclovir is not approved for reduction of transmission of HSV-2, its manufacturers are considering pursing this indication.

The herpes simplex virus is responsible for a variety of infections including genital herpes as well as cold sores. Various antivirals, including acyclovir, valacyclovir and famciclovir, are prescribed for treatment of initial episodes of genital herpes and recurrent herpetic outbreaks. These antivirals have proved to decrease the length of herpetic outbreaks and reduce asymptomatic viral shedding. However, asymptomatic viral shedding is a significant mode of HSV-2 transmission and until recently, data were not available regarding antiviral use in decreasing transmission of the virus. Data now indicate that HSV-2 transmission can be significantly decreased with suppressive valacyclovir treatment.

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