By Stan Deresinski, MD, FACP, FIDSA
Clinical Professor of Medicine, Stanford University
SYNOPSIS: Viral shedding after a first episode of genital herpes simplex virus type 1 (HSV-1), which is gradually replacing herpes simplex virus type 2 (HSV-2) as the major cause of genital infection, occurred in 12.1% at weeks 8-12 and decreased to 7.1% at the end of one year.
SOURCE: Johnston C, Magaret A, Son H, et al. Viral shedding 1 year following first-episode genital HSV-1 infection. JAMA 2022;328:1730-1739.
Our understanding of genital herpes virus infection has been based largely on knowledge of herpes simplex virus type 2 (HSV-2) infection, which has been the dominant etiology. However, the epidemiology is shifting with increasing prevalence of herpes simplex virus type 1 (HSV-1) as a cause of genital infection, the natural history of which is addressed in this study by Johnston and colleagues.
The investigators enrolled 82 nonpregnant individuals within eight weeks of a first clinical episode of genital HSV-1 infection and who were seronegative for both HSV-2 and human immunodeficiency virus (HIV). Their median age was 26 years, and 54 (65.9%) were women. Ten (12.2%) indicated they had previously had oral HSV infection.
Based on antibody testing, the first episode was primary in 42 (51.2%) cases, non-primary in 23 (28.1%) cases, and the remainder were unknown. Twelve weeks after their first HSV-1 infection episode, only two (2.5%) patients were HSV-1 seronegative. All subjects remained HSV-2 seronegative over 52 weeks.
Subjects maintained a daily diary of symptoms and obtained daily oral and genital swabs between eight and 12 weeks (session 1) and between 48 and 52 weeks (session 2) after the first episode of genital HSV-1. Genital HSV-1 shedding was detected by polymerase chain reaction (PCR) on 225 of 2,264 days (12.1%) during session 1, but this decreased by almost one-half to 122 of 1,719 days (7.1%) during session 2. Genital lesions emerged much less frequently, occurring during 65 of 2,459 days (2.6%) of session 1 and 72 of 1,872 days (3.8%) of session 2. Shedding was significantly more frequent in patients with primary infection than in those with non-primary infection, with a relative risk of 2.75 (95% confidence interval [CI], 1.40 to 5.44).
Oral shedding occurred on 3.9% of days and varied little over time. Oral lesions occurred on only 0.4%. CD4 and CD8 HSV-1-specific T cell responses were maintained throughout.
COMMENTARY
Life was easier when all you had to remember was that HSV-1 caused oral infections while HSV-2 caused anogenital infections. Life and viruses, however, move on, as evidenced by the gradual replacement of HSV-2 by HSV-1 as the cause of genital herpes.
A key element in this epidemiological transition has been a progressive decline in HSV-1 infections, as reflected in seropositivity rates, particularly in adolescents who are, as a result, at increased risk of infection at sexual debut. In some groups, such as young heterosexual women and college students, HSV-1 has become a major cause of anogenital infections. Recent data indicate that almost one-fourth of incident HSV-1 infections in late adolescence and young adulthood were genital and most were related to oral-genital sex. One indirect effect of this changing epidemiology is that HSV-1 is reported to cause more cases of neonatal HSV infection than HSV-2 in the Americas, Europe, and the Western Pacific.
Of note is that 10 (8.2%) subjects reported having oral HSV infection which, if correct, suggests that prior HSV-1 infection may not protect against subsequent genital infection with this virus. In addition, some patients had their first genital episode of HSV-1 infection despite having “fully developed” antibody targeting this virus.
An important finding in this study by Johnston and colleagues is that HSV-1 shedding occurred on 12.1% of days by weeks 8-12 after an initial clinical episode and this decreased 7.1% during weeks 48-52. In contrast, genital HSV-2 shedding occurs in one-third in the year after a first clinical episode and only decreases to one-half that level over 10 years.
The data developed by Johnston and colleagues provide the basis for effective counseling of individuals regarding the risk of clinical recurrence and likelihood of shedding and, thus, of transmission to sexual partners. In addition, the finding that HSV-1 shedding is most frequent in the first months after an initial clinical episode suggests that consideration may be given to prophylaxis, at least during this period.
Since antibody testing cannot reliably distinguish between viral types, effective counseling depends on the use of PCR during the initial clinical episode to distinguish HSV-1 from HSV-2. However, serological testing provides useful information, since primary infection is associated with a greater risk of viral shedding.
