Getting a Better Grasp on Genital HSV-1

One current challenge in the field of genital herpes is improving the diagnosis and management of patients with genital infections caused by herpes simplex type 1 (HSV-1).

While HSV-1 and -2 are closely related, they differ in important ways. Perhaps most notably, up until now HSV-2 has overwhelmingly been the more prevalent cause of genital herpes infections. Accordingly, researchers and clinical experts have spent a great deal more time and resources studying HSV-2—looking at everything from natural history to diagnostic tools to drug development.

In the last two decades, however, the field has seen a marked increase in the number of genital herpes cases caused by HSV-1. Previously HSV-1 was associated almost entirely with oral-facial herpes, but by the end of the 1990s a significant percentage of new genital herpes diagnoses were being identified as HSV-1 cases. According to Dr. Christine Johnston, MD, of the University of Washington (UW), modeling studies show that by 2050 an increasing proportion of HSV-1 infections will be acquired sexually—a change that will largely affect adolescents and young adults. “Historically, HSV-1 had been acquired in childhood or adolescence,” says Johnston. “But now we’re having less acquisition during this period and people are getting their first exposure to HSV-1 when they initiate sexual activity.”

Johnston and her colleagues, including staff at the UW Virology Research Clinic, have been tracking HSV-1’s changing epidemiology and have published a number of related papers. Speaking to a webinar hosted by Herpes Cure Advocacy in March, Johnston outlined the many areas in which scientists are seeking new empirical data on genital HSV-1. This research has touched on clinical management, immunology studies, behavioral impacts, and more.

For a study published in JAMA in 2022, Johnston’s group enrolled 82 subjects who had no prior herpes symptoms but were found to be genital HSV-1 positive by viral culture or polymerase chain reaction (PCR). Researchers then had these subjects collect genital and oral swabs daily for months 2 and 3 after the first episode and again for months 11 and 12. Patients also completed diaries to collect additional information.

About half of the subjects had a documented “primary episode,” meaning a newly acquired HSV infection with no evidence of prior HSV antibodies. The other half was considered to have a “nonprimary first episode,” meaning that they had previously acquired herpes and therefore had some degree of immune protection.

This distinction turned out to be a critical factor in the results of Johnston’s study. Her team found that genital HSV-1 subjects in the “primary episode” category had significantly greater disease burden than non-primary subjects, with more lesions and higher rates of viral shedding.

The study found viral shedding at both genital and oral sites. Shedding frequency from the genital area was 12% of days in the month 2-3 data, and fell to 7% at month 11-12. Oral shedding, meanwhile, remained steady at roughly 4% to 5% of days through both sessions. With both genital and oral shedding, rates were higher for subjects presenting with a true primary.

“On average, recurrences are less frequent for HSV-1 compared to HSV-2,” says Johnston.

“With HSV-1, people will have median of 1 recurrence in first year, a figure that falls somewhere between zero and 1 after that first year.” With genital HSV-2, historical studies would project the average number of recurrences at 5 in year 1, with a likely steady decline over time.

Overall, comparing the lab results for the 82 HSV-1 patients with historical data on people with genital HSV-2, the HSV-1 group in Johnston’s study experienced fewer lesions and lower rates of viral shedding.

Johnston believes more studies are needed to sort out some of the clinical challenges to HSV-1, pointing to the need for better serologic tests, a better understanding of the role of antiviral treatment in genital HSV-1, and more data on ways to reduce transmission risk to partners.

– Charles Ebel

The full slide deck for Dr. Christine Johnson’s webinar presentation is available here, including answers to several frequently asked patient questions.