Characterizing herpes simplex virus type 1 and type 2 seroprevalence declines and epidemiological association in the United States

Objective: Assessing the epidemiological association between herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) infections in the United States, and characterizing the trends in the standardized HSV-1 and HSV-2 antibody prevalences (seroprevalences), 1999–2016. Methods: Source of data was the cross-sectional and nationally-representative biennial surveys of the National Health and Nutrition Examination Survey (NHANES). All nine NHANES rounds for 1999–2016 were included in analysis. Datasets of these rounds were combined and analyzed accounting for survey design and applying weighting procedures. Logistic regressions were used to identify associations with seropositivity. Sensitivity analyses were conducted. Results: Odds of HSV-1 infection declined by 2.84% (95% CI: 1.70%-4.00%) annually among men, and by 2.22% (95% CI: 1.23%-3.21%) among women. Declines were highest at younger ages. Odds of HSV-2 infection declined by 2.23% (95% CI: 0.71%-3.82%) annually among men, and by 2.89% (95% CI: 1.57%-4.28%) among women. Odds ratio of the association between HSV-2 and HSV-1 seropositivity was 0.71 (95% CI: 0.60–0.84) for men and 0.81 (95% CI: 0.72–0.91) for women, after adjustment for age, ethnicity, and year. Conclusion: HSV-1 and HSV-2 seroprevalences showed a strong declining trend for at least two decades, for both sexes and for the different ethnicities, possibly reflecting improvements in hygiene and living conditions (for HSV-1), and safer sexual behavior (for HSV-2). HSV-1 seroprevalence declines are most pronounced among young individuals. There is evidence for cross protection between the two infections, suggestive of HSV-1 seropositivity being partially protective against HSV-2 infection.