Genital Shedding of Herpes Simplex Virus Among Symptomatic and Asymptomatic Persons With HSV-2 Infection

Abstract

Context Since HSV-2 antibody tests have become commercially available, an increasing number of persons learn that they have genital herpes through serologic testing. The course of natural history of HSV-2 in asymptomatic, seropositive persons is uncertain. Objective To evaluate the virologic and clinical course of HSV genital shedding among participants with symptomatic and asymptomatic HSV-2 infection. Design, Setting and Participants Cohort of 498 immunocompetent HSV-2 seropositive persons enrolled in prospective studies of genital HSV shedding at the University of Washington Virology Research Clinic, Seattle, Washington, and Westover Heights Clinic in Portland, Oregon, between 1992 and 2008. Each participant obtained daily self-collected swabs of genital secretions for ≥ 30 days. Main Outcome Measurement The rate of viral shedding measured by quantitative real-time fluorescence polymerase chain reaction (PCR) for HSV DNA from genital swabs. Results HSV was detected on 4,753 of 23,683 days (20.1%; 95% CI, 18.3 to 22.0) in persons with symptomatic genital HSV-2 infection compared with 519 of 5,070 days (10.2%; 95% CI, 7.7 to 13.6) in persons with asymptomatic infection, p<0.001. Subclinical shedding rates were higher in persons with symptomatic infection compared with asymptomatic infection (2,708 of 20,735 days (13.1%; 95% CI, 11.5 to14.6) vs. 434 of 4,929 days (8.8%; 95% CI, 6.3 to 11.5), p<0.001. However, the amount of HSV detected during subclinical shedding episodes was similar (median 4.3 [IQR 3.1-5.6] log10 copies in the symptomatic infection group vs. 4.2 [IQR, 2.9-5.5], p=0.27 in the asymptomatic infection group). Days with lesions accounted for 2,045 of 4,753 days (43.0%; 95% CI, 39.8 to 46.5) with genital viral shedding among persons with symptomatic genital HSV-2 infection compared with 85 of 519 days (16.4%; 95% CI, 11.2 to 23.9) among persons with asymptomatic infection, p<0.001. Conclusions Persons with asymptomatic HSV-2 infection shed virus in the genital tract less frequently than persons with symptomatic infection, but much of the difference is attributable to less frequent genital lesions, as lesions are accompanied by frequent viral shedding.

HSV-2: in pursuit of a vaccine

“…Although the first study of a recombinant gD2 vaccine adjuvanted with alum reduced the rate of virologically confirmed recurrences (106), later studies of glycoprotein vaccines failed to replicate that effect (107). Unlike the prophylactic vaccine studies, shedding data from our group indicate that the pivotal therapeutic vaccine studies can be performed efficiently with fewer than 100 individuals if viral shedding is used as an endpoint (33), whereas prophylactic vaccination studies require a much larger sample size. Viral shedding rate and quantity of virus shed could serve as useful surrogate endpoints for recurrence rate and transmission likelihood in studies of therapeutic vaccines as well.…”

“…This implies host responses that likely involve cell-intrinsic and -extrinsic mechanisms of innate as well as acquired immunity. In studies in which HSV-2-infected persons collect daily genital swabs, HSV is detected on a median of 12%-28% of days (32) and is found on 10% of days even among persons with asymptomatic HSV-2 infection (33). Many of these shedding episodes occur in the absence of lesions or symptoms (known as subclinical shedding; ref.…”

Prevalence and Determinants of Herpes Simplex Virus Type 2 (HSV-2)/Syphilis Co-Infection and HSV-2 Mono-Infection among Human Immunodeficiency Virus Positive Men Who Have Sex with Men: a Cross-Sectional Study in Northeast China

“…Transmission between homosexuals has continued to increase among annual reported HIV cases, rising from 0.3% before 2005 to 25.8% in 2014 (2). Herpes simplex virus type 2 (HSV-2) is one of the most common sexually transmitted pathogen and the most frequent cause of genital ulcers (3). HSV-2 and HIV have a synergistic relationship in that HSV-2 infection increases the susceptibility to and transmission of HIV, and HIV infection increases the susceptibility to HSV-2 infection and HSV-2 genital shedding (3,4).…”

Low prevalences of HIV infection and HSV genital shedding in the general adult female population in Senegal

“…The low prevalence of HSV-2 in adult Senegalese women contrasts with the higher HSV-2 seroprevalence reported in the general populations living in neighbouring countries [22][23][24], as well as in central or southern Africa [25][26][27][28][29]. The low rate (1.3%) of women shedding HSV-2 DNA in our study population clearly reflects the low HSV-2 seroprevalence of this population, since only a minority of HSV-2-infected individuals usually shed herpes DNA in their genital secretions [30].…”