Herpes Simplex Virus Type 2 (HSV-2) Western Blot Confirmatory Testing Among Men Testing Positive for HSV-2 Using the Focus Enzyme-Linked Immunosorbent Assay in a Sexually Transmitted Disease Clinic

Objective: The objective of this study was to define the positive predictive value (PPV) of the Focus herpes simplex virus type 2 (HSV-2) enzyme-linked immunosorbent assay (ELISA) in a low HSV-2 prevalence population and to develop a new test interpretation algorithm. Methods: HSV-2 Western blots were performed on sera from male sexually transmitted disease clinic patients testing HSV-2 ELISA-positive and used to define a new class of indeterminate HSV-2 ELISA result. HSV-2 Western blots were then prospectively performed on sequential sera with indeterminate HSV-2 ELISAs. Results: Ninety-one (84%) of 108 HSV-2 ELISA-positive sera tested HSV-2 Western blot-positive. Western blot positivity was more common in men without herpes simplex virus type 1 (HSV-1) antibody than in those with HSV-1 antibody (93% vs 76%, P = 0.02) and in men with a history or clinical evidence of genital lesions (88% vs 80%, P = 0.30). Selectively raising the ELISA index value defining HSV-2 positivity from >1.1 to ≥3.0 either among HSV-1-positive men or among those without a history or clinical evidence of genital lesions increased the PPV to ≥93%. Prospective evaluation of an algorithm incorporating HSV-1 serostatus found that 11 of 70 persons with indeterminate HSV-2 ELISAs were Western blot-positive. Conclusions: Clinicians should consider selectively using a higher index value to define Focus ELISA HSV-2 positivity based on either HSV-1 serostatus or clinical circumstances.