For the first time, scientists have found that genital herpes can reactivate even during high dose antiviral therapy, a discovery which they say underlines that new class of treatments are needed to combat this common infection that affects one in five people.
The study by a team from the University of Washington’s Virology Research Clinic in Seattle was based on three trials that involved 113 patients who received antiviral therapy to treat genital herpes, or herpes simplex virus type 2 (HSV—2).
The results, published in The Lancet, showed that the virus can reactivate in “breakthrough episodes” even when doses of antiviral therapy are high.
The patients in the trials were given either a standard dose or a high dose of available medications — aciclovir and valaciclovir — to treat their infection.
The results showed that short episodes of subclinical shedding (symptom free) persist with both standard-dose and high-dose aciclovir and valaciclovir.
Although HSV shedding was reduced by 50 per cent with the highest doses of valaciclovir compared with standard dose valaciclovir, the rate of breakthrough shedding episodes did not change — about 16-20 episodes per year.
The researchers, led by Dr Christine Johnston said: “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.”
Symptoms of HSV-2 infection include ulcers in the skin or mucus membranes of the mouth, lips, or genitals. However, most people with this infection do not have obvious symptoms, but even so, can shed the virus and transmit it to sexual partners. Once someone is infected, HSV-2 is able to hide in the nervous system of the host, enabling it to reactivate periodically in those infected.
During re-activation, the scientists said, the virus in a nerve cell is transported along the nerve to the skin, where new replication and “shedding” occur and cause new sores.
Intensive genital secretion collection shows that HSV shedding episodes are three-times more frequent than was previously realised.
The authors concluded: “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.”
Experts also believe that development of new classes of antiviral drug such as helicase-primase inhibitors is important but such drugs would need good long-term coverage and adherence to successfully prevent shedding and onward transmission of HSV-2.
