Persistent genital HSV-2 shedding even in patients with long duration of infection

Rates of genital HSV-2 shedding decrease the longer a patient has had the disease, US investigators report in the January 15^th edition of the Journal of Infectious Diseases.

However patients who had been infected with genital herpes for ten or more years were still shedding the virus on 17% of days. Moreover, even among patients with longer duration of infection, levels of virus present in their genital mucosa were potentially infectious.

“HSV-2 shedding frequency, clinical recurrences, and HSV-2 shedding quantity remain at high levels for many years following infection,” write the investigators.

Herpes simplex virus-2 (HSV-2) is the main cause of genital herpes, one of the most common sexually transmitted infections.

Many patients find that their first attack of HSV-2-associated genital herpes is the most severe, and recurrences of disease are most likely to occur in the first year after the initial attack. However, infection with the virus is life-long and this can lead the reappearance of lesions many years after the first episode of disease.

It is currently unclear if genital shedding of HSV-2 decreases over time. A better understanding of this issue could help physicians provide their patients with appropriate treatment, support and information about the potential risk of infection for their sex partners.

Therefore investigators in the Pacific Northwest of the US undertook a prospective study involving 377 adults with genital HSV. The date of the first episode of genital herpes was known for each of the patients, and they were recruited between 1992 and 2008.

To find out how often patients were shedding the virus, individuals were instructed to perform daily ano-genital swabs for at least 30 comsecutive days.

The patients had a median age of 39 years and 89% were white. Women comprised almost two-thirds (62%) of the sample, and 12% identified as gay or lesbian. None of the participants were HIV-positive.

Median age at the first episode of genital herpes was 27, and the median time since the first occurrence of the disease and recruitment to the study was seven years.

A total of 25,752 days with genital swabs were available for analysis.

Virus was detected at least once in 86% of participants, 81% shed the virus without lesions on at least one day, and 68% had genital lesions on one or more days.

Overall, HSV-2 was shed on 21% of days.

The proportion of days on which virus was shed decreased the longer a patient had had genital herpes.

In the year following the first attack, virus was shed on 34% of days. This fell to 21% of days for patients who had had their first attack between one and nine years, and to 17% of these days for individuals whose first episode of the disease was ten or more years ago. These reductions were significant (p = 0.001).

Shedding of the virus was highest among patients whose first attack of genital herpes was within the last year (26%% of days). It fell to 13% for individuals whose first episode of disease was up to nine years earlier, and to 9% for patients who first experienced genital herpes ten or more years ago. These differences were also significant (p < 0.001).

Lesions were present on 16% of days among patients whose first episode of disease was less than a year ago; on 14% for those who had had the infection for between one and nine years; and on 12% of days for individuals whose first disease was ten or more years ago. The reductions were significant in the investigators’ first analysis (p = 0.05), but of only borderline significance when possible confounding factors were taken into account.

HSV-2 genital viral load was highest for patients with the shortest duration of disease (4.9 log₁₀ copies/ml), but fell with longer duration of infection (one to nine years, 4.7 log₁₀ copies/ml, ten or more years, 4.6₁₀ log copies/ml).

However the investigators emphasise, “the mean number of copies in our study remain well above 3 log₁₀ copies/ml in all time groups, which is likely a sufficient quantity to transmit infection.”

Longer time since the first attack of genital herpes was also associated with a significant (p = 0.007) reduction in the frequency and duration of clinical disease (under one year, 10 days; up to nine years, 7 days; ten or more years, 6.5 days).

Non-white race was associated with lower rates of shedding, recurrence of clinical disease, and shorter duration of attacks. But the investigators noted that only eleven individuals were non-white and were therefore cautious about the importance of these findings.

“Most persons still shed HSV-2 either clinically or subclinically at high rates for years after infection,” comment the investigators. They believe their “findings have important implications for the long-term management of genital HSV and may warrant strategies such as long-term use of antiviral medications for clinical suppression and continued condom use to reduce transmission to partners.”