Herpes Shedding Rate Can Stand in For Genital Lesions as a Study Outcome

For years, studies involving the herpes simplex virus focused on the effectiveness of potential treatments at banishing the genital lesions that were a hallmark of the disease. However, it’s now recognized that the shedding of herpes virus, even in the absence of genital lesions, can also be a reliable indicator of new or ongoing infection that warrants treatment.

A recent study out of the University of Washington and the Fred Hutchinson Cancer Center in Seattle confirms that herpes shedding can be an appropriate surrogate outcome in clinical trials of herpes therapies. The team looked at data from trials in which a total of 674 subjects with herpes had swabbed their anogenital regions and collected specimens every day for a period of time. There were 3 different cohorts in this study. One cohort had not used antiviral drugs for at least a week before the study began; the second cohort had participated in a randomized, double-blinded trial of the antiviral drug pritelivir; and the third cohort had participated in a randomized, double-blinded trial of acyclovir/valacyclovir.

The researchers found a strong correlation between rates of herpes virus shedding (i.e., the virus was found in the swabbed specimens) and rates of genital lesions, with shedding able to predict up to 82% of antiviral drugs’ impact on the clinical outcome.

Using genital lesions alone to determine whether or not a particular medication is effective against herpes is tricky, the researchers say, because these lesions are not always present. Lesions actually are less likely to occur than genital shedding; in this study, genital shedding was found on 17% of the days tested, while genital lesions were reported on just 10% of them. Overall, at least two-thirds of the study’s participants had shown genital shedding at some point but only 40% ever had any evidence of genital lesions. Because individual participants showed consistency in shedding rates over time, “[W]e conclude that HSV shedding is a consistent measure of HSV disease severity,” the researchers write. “[T]he association of shedding frequency with lesion frequency and the ability of the shedding rate to predict the future frequency of the lesion rate lends further credibility to the biological connection and the usefulness of shedding to predict a clinical outcome.”

Will this study help change the way herpes is diagnosed? At least one expert hopes so. “One of the problems is that the testing we have for herpes is not terribly good,” Kenneth Fife, MD, PhD, medical director of SAFE Health, Inc., a Santa Monica, California-based organization that uses technology to improve people’s sexual health, told Contagion^®. “The antibody test for [the virus] is not very accurate.” If the average clinician had access to a test that included a patient’s level of genital shedding, as was used in this study, Fife feels that people could be diagnosed more efficiently. “We’d like to offer this kind of testing to patients,” he said. “We wish we had better tools.”

According to the researchers, using genital shedding as a surrogate outcome allows studies to proceed with fewer participants, as more people with herpes experience shedding than lesions. Without the need to recruit more participants, studies could potentially be conducted more quickly and cheaply. The Seattle team noted that its study did have a couple of limitations, including the fact that lesions were self-reported (and thus potentially underreported). Also, longer monitoring times in future trials (more than 25 days) might allow results to be even more precise.