Immunocompromise and herpes simplex virus type 1 encephalitis (HSVE): a nationwide cohort and case-control study (S25.009)

Abstract

<h3>Objective:</h3> We aim to determine whether a relationship exists between immunocompromise as defined by autoimmune disease or immunosuppressive and immunomodulatory medications in patients and incident HSVE. <h3>Background:</h3> Among infectious etiologies of encephalitis, herpes simplex virus type 1 (HSV-1) is commonest. The association between immune status and HSVE is unclear. Using a U.S. Medicaid database of 75.6 million persons, we evaluated the association between HSVE and autoimmune conditions, exposure to immunosuppressive and immunomodulatory medications, and other medical comorbidities. <h3>Design/Methods:</h3> We used the U.S. Medicaid Analytic eXtract Database between the years of 2007–2010 from the 29 most populated American states. We first examined the crude incidence of HSVE in the population. We then age- and sex-matched adult cases of HSVE with a sufficient enrolment period to a larger control population without HSVE. In a case-control analysis, we examined the association between HSVE and exposure to both autoimmune disease and immunosuppressive/immunomodulatory medications. Analyses were conducted with conditional logistic regression progressively adjusting for sociodemographic factors, Charlson comorbidity index, and non-autoimmune comorbidities. <h3>Results:</h3> Incidence of HSVE was ~3.01 per 10⁵ person-years among adults. A total of 951 HSVE cases and 95,100 age- and sex-matched controls were compared. The HSVE population had higher rates of medical comorbidities than the control population. The association of HSVE and autoimmune conditions was strong, adjusted OR 2.6 (95% CI [2.2, 3.2]). The association of HSVE and immunomodulating medications had an OR of 2.2 [1.9, 2.6], also after covariate adjustment. When both exposures were included in regression models, the associations remained robust: 2.3 [1.9, 2.7] for autoimmune disease and 2.0 [1.7, 2.3] for immunosuppressive and immunomodulatory medications. <h3>Conclusions:</h3> In a large, national population, HSVE is strongly associated with pre-existing autoimmune disease and exposure to immunosuppressive and immunomodulatory medications. The role of antecedent immune-related dysregulation may have been underestimated to date. <b>Disclosure:</b> Dr. Tang has received personal compensation for serving as an employee of Third Rock Ventures. Dr. Bhattacharyya has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alexion Pharmaceuticals. Dr. Bhattacharyya has received personal compensation in the range of $5,000-$9,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Continuum. The institution of Dr. Bhattacharyya has received research support from Alexion Pharmaceuticals. The institution of Dr. Bhattacharyya has received research support from National Institute of Health. The institution of Dr. Bhattacharyya has received research support from UCB. Dr. Bhattacharyya has received publishing royalties from a publication relating to health care. Dr. Bhattacharyya has received publishing royalties from a publication relating to health care. Dr. Bhattacharyya has received publishing royalties from a publication relating to health care. Dr. Miyawaki has received personal compensation in the range of $50,000-$99,999 for serving as an officer or member of the Board of Directors for Family Health, Inc.. Dr. Miyawaki has received personal compensation in the range of $10,000-$49,999 for serving as an Expert Witness for Morrison and Mahoney. Dr. Miyawaki has stock in Cincinnati Bengals. Dr. Miyawaki has received publishing royalties from a publication relating to health care. Dr. Miyawaki has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant with US Department of Health and Human Services. Dr. Yoshida has received personal compensation for serving as an employee of OM1, Inc. Dr. Yoshida has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for OM1, Inc. Dr. Wilcox has nothing to disclose. Karen Costenbader has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Amgen. Karen Costenbader has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Lilly. Karen Costenbader has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Glaxo Smith Kline. Karen Costenbader has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for AstraZeneca Pharmaceuticals LP. Karen Costenbader has received personal compensation in the range of $0-$499 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Arthritis and Rheumatology. Karen Costenbader has received personal compensation in the range of $0-$499 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Uptodate. Karen Costenbader has stock in Neutrolis. The institution of Karen Costenbader has received research support from Gilead. The institution of Karen Costenbader has received research support from Exagen. The institution of Karen Costenbader has received research support from Merck. Karen Costenbader has received personal compensation in the range of $0-$499 for serving as a grant reviewer with NIH. Prof. Solomon has nothing to disclose. Mr. Guan has nothing to disclose. Miss Lahey has nothing to disclose.