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Risk of Diffuse Infiltrative Lymphocytosis Syndrome in HIV-Infected Patients

A Nationwide Population-Based Cohort Study

Chen, Marcelo MD, PhD*,†,‡; Yen, Yung-Feng MD, MPH, PhD‡,§,║; Lan, Yu-Ching PhD; Jen, I-An MD, MPH‡,#; Chuang, Pei-Hung PhD‡,**,††; Lee, Chun-Yuan MD‡‡; Lee, Yun MS; Lin, Yu-An MS; Arthur Chen, Yi-Ming MD, ScD‡,§§

JAIDS Journal of Acquired Immune Deficiency Syndromes: October 1, 2018 - Volume 79 - Issue 2 - p 158–163
doi: 10.1097/QAI.0000000000001802

Objective: Diffuse infiltrative lymphocytosis syndrome (DILS) is the term used for sicca syndrome in HIV patients and has similar clinical manifestations as Sjögren syndrome. In this nationwide population-based study, we aimed to determine the association between HIV infection and DILS in the Taiwanese population.

Methods: The National Health Insurance Research Database was searched for cases of DILS in HIV-infected individuals diagnosed between January 1, 2000, and December 31, 2012. The incidence of DILS and the factors associated with DILS in people living with HIV/AIDS (PLWHA) were determined.

Results: A total of 20,364 PLWHA were followed, and 57 (0.28%) individuals had new-onset DILS. The incidence rate of DILS in PLWHA was 0.56/1000 person-years. One (0.11%) female HIV patient with highly active antiretroviral therapy (HAART) and 24 (2.99%) without HAART had incident DILS, whereas 22 (0.17%) male HIV patients with HAART and 10 (0.17%) without HAART had incident DILS. Hypertension increased the risk of incident DILS. HAART decreased the risk of DILS, but this relationship somewhat attenuated in an adjusted model. None of the patients taking emtricitabine, raltegravir, darunavir, enfuvirtide, or tipranavir developed DILS. Lopinavir was associated with a decreased risk of DILS (adjusted hazard ratio = 0.10, 95% confidence interval: 0.01 to 0.84), whereas zalcitabine was associated with an increased risk of DILS (adjusted hazard ratio = 13.7, 95% confidence interval: 2.18 to 85.9).

Conclusions: DILS is a rare disease found in PLWHA. Hypertension is a risk factor for incident DILS, and HAART could affect the pathogenesis of DILS. Zalcitabine was the only antiretroviral agent found to increase the risk of DILS.

*Department of Urology, Mackay Memorial Hospital, Taipei, Taiwan;

Department of Cosmetic Applications and Management, Mackay Junior College of Medicine, Nursing and Management, Taipei, Taiwan;

Center for Infectious Disease and Cancer Research, Kaohsiung Medical University, Kaohsiung, Taiwan;

§Section of Infectious Diseases, Taipei City Hospital, Taipei, Taiwan;

School of Medicine, National Yang-Ming University, Taipei, Taiwan;

Department of Health Risk Management, China Medical University, Taichung, Taiwan;

#Department and Institute of Public Health, National Yang-Ming University, Taipei, Taiwan;

**Center for Prevention and Treatment of Occupational Injury and Diseases, Taipei Veterans General Hospital, Taipei, Taiwan;

††Division of Clinical Toxicology and Occupational Medicine, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan;

‡‡Division of Infectious Diseases, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan; and

§§Department of Microbiology, Institute of Medical Research, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.

Correspondence to: Yi-Ming Arthur Chen, MD, ScD, Center for Infectious Disease and Cancer Research, Kaohsiung Medical University, Kaohsiung 807, Taiwan (e-mail:

Supported by Kaohsiung Medical University “Aim for the Top Universities Grant” KMUTP105-E01 and “Global Networking Talent Plan” grants 105KMUOR02 and 105KMUOR05.

The authors have no funding or conflicts of interest to disclose.

This study is based in part on data from the National Health Insurance Research Database provided by the Bureau of National Health Insurance, Department of Health and managed by National Health Research Institutes.

Received October 29, 2017

Accepted June 07, 2018

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