Longitudinal Reliability of Focus Glycoprotein G-Based Type-Specific Enzyme Immunoassays for Detection of Herpes Simplex Virus Types 1 and 2 in Women

Abstract

Serologic assays that utilize herpes simplex virus (HSV) type-specific glycoproteins G-1 (HSV-1) and G-2 (HSV-2) to discriminate between antibodies against HSV-1 and HSV-2 are sensitive and specific. However, the high rates of seroreversion, defined as the change in an individual's antibody status from positive to negative over time, previously reported in longitudinal evaluations of glycoprotein G type-specific tests suggests that their use in HSV acquisitional studies would be problematic. To further explore the reliability of the glycoprotein G-based serologic tests, we evaluated HSV-1 and HSV-2 enzyme immunoassays from Focus Technologies in a longitudinal cohort of 1,207 young women from Pittsburgh, Pa. On enrollment of the women in the study, HSV-1 and HSV-2 antibodies were detected in 46.6 and 24.9% of the women, respectively. Among the women with at least three visits, 3.4% (15 of 447) of those who were HSV-1 antibody positive had a subsequent negative result while fewer than 1% (2 of 227) of those who were HSV-2 antibody positive seroreverted. The median of mean positive index values for women who seroreverted to HSV-1 antibody was lower than that for women who remained seropositive (1.25 versus 7.06; P < 0.001). Similarly, the median of mean positive index values for women whose HSV-2 antibody status reverted from positive to negative was lower than that for those women who did not serorevert (1.83 versus 7.46; P ‫؍‬ 0.02). Comparative Western blot analysis demonstrated that the lower positive index values, seen more often among the HSV seroreverters, often signified false-positive immunoassay results. Overall, the seroreversion rates were low; the use of glycoprotein G-based serologic tests for the measurement of HSV-1 and HSV-2 antibodies in incidence studies therefore appears warranted.It is estimated that over 50 million people in the United States have genital herpes (7). A 30% increase in the seroprevalence of herpes simplex virus type 2 (HSV-2) infection in this country over the past two decades demonstrates that the epidemic continues unabated (9). Furthermore, an increasing proportion of primary genital herpes infections are caused by herpes simplex virus type 1 (HSV-1) (11). The ability to diagnose these HSV infections has been enhanced by the advent of type-specific serologic tests. HSV-1 and HSV-2 exhibit a high degree of cross-reactivity, but an envelope glycoprotein, gG, is antigenically distinct between the two viruses, and the typespecific antibody response to gG provides evidence of infection with HSV-1 or HSV-2 or both (5). Type-specific gG serologic assays include Western blotting (2, 6), immunoblot strips (21), and enzyme-linked immunosorbent assays (ELISAs) (14,16,17). Although the Western blot assay is considered to be the "gold standard," it is expensive and labor-intensive and its interpretation is operator dependent (5). In comparison, ELISAs are quicker, less expensive, and better suited for highvolume screening.The objective of the present study was to determine the longitudin...

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