According to a study in which three trials of antiviral therapy to treat genital herpes were combined, the herpes simplex virus type 2/HSV-2 can reactivate in ‘breakthrough episodes’ even when doses of antiviral therapy are high. The study is published Online First in The Lancet and suggests that new therapies should be conducted to successfully prevent further transmission of this common infection, which affects one in five people.

HSV-2 infection is characterized through ulcers in the skin or mucus membranes of the mouth, lips, or genitals, and even though most people do not show obvious symptoms, they are still able to shed the virus and transmit it to sexual partners.

HSV-2 hides in the nervous system of the infected host and can reactivate periodically. When the virus is re-activated in a nerve cell, it is transported along the nerve to the skin, where it is replicated anew causing ‘shedding’ and new sores. Intensive genital secretion collection demonstrates that HSV shedding episodes are three-times more frequent than was previously thought.

Dr. Christine Johnston at the University of Washington Virology Research Clinic in Seattle, WA, USA, and her team conducted three separate but complementary open-label crossover studies involving 113 patients. They compared giving patients no medication with those who were administered the standard-dose of aciclovir 400 mg twice daily.

Other patients received the standard dose of valaciclovir 500 mg daily compared with a high dose of aciclovir 800 mg three times daily, and those who were given a standard-dose of valaciclovir compared with a high dose of valaciclovir 1 g three times daily.

The findings demonstrated that short episodes of subclinical, i.e. symptom free shedding persist with both standard-dose and high-dose aciclovir and valaciclovir and even though HSV shedding was lowered by 50% with the highest doses of valaciclovir compared with the standard dose of valaciclovir, the rate of breakthrough shedding incidences remained unchanged with approximately 16 to 20 incidences each year.

The researchers explain:

“Our finding that high-dose valaciclovir increases the kinetics of viral clearance, but not expansion, supports the hypothesis that these antiviral drugs do not suppress the release of virions into the genital tract. That we could not eliminate or even alter the frequency of shedding episodes with high-dose valaciclovir suggests that the maximum benefit of shedding reduction has probably been reached for currently available antiviral drugs.”

They summarize their findings concluding, that:

“Although currently available anti-HSV therapy benefits patients by preventing clinical HSV recurrences, suppressive therapies with greater potency, including antiviral drugs or immunotherapy in the form of therapeutic vaccines, are needed to provide substantial public health benefits, such as prevention of HSV-2 transmission and HIV-1 acquisition and transmission.”

According to a linked comment by Dr. Philippe Van de Perre and Dr. Nicolas Nagot INSERM U 1058 in Montpellier, France, and the Université Montpellier 1 in Montpellier, France, even though the development of new antiviral drug classes, such as helicase-primase inhibitors is important, such drugs would require a good long-term coverage and adherence to successfully prevent shedding and onward transmission of HSV-2.

They explain and conclude:

“These needs are unlikely to be met because about 20% of the general population is infected with HSV-2 in the USA and Europe, most of whom have no clinical need for antiherpetic therapy. Alternative control tools, such as immunotherapeutic strategies (therapeutic vaccines), are in preclinical development, but they are hampered by the absence of an adequate animal model and the lack of commitment from pharmaceutical companies and the public sector.”

Written by Petra Rattue