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Association of HIV and Opportunistic Infections With Incident Stroke: A Nationwide Population-Based Cohort Study in Taiwan

Yen, Yung-Feng MD, MPH, PhD; Chen, Marcelo MD, PhD; Jen, Ian MD, MPH; Lan, Yu-Ching PhD; Chuang, Pei-Hung PhD; Liu, Yen-Ling MPH; Lee, Yun MPH; Chen, Yi-Ming Arthur MD, ScD

JAIDS Journal of Acquired Immune Deficiency Syndromes: February 1st, 2017 - Volume 74 - Issue 2 - p 117–125
doi: 10.1097/QAI.0000000000001216

Background: HIV-associated vasculopathy and opportunistic infections (OIs) might cause vascular atherosclerosis and aneurysmal arteriopathy, which could increase the risk of incident stroke. However, few longitudinal studies have investigated the link between HIV and incident stroke. This cohort study evaluated the association of HIV and OIs with incident stroke.

Methods: We identified adults with HIV infection in 2000–2012, using the Taiwan National Health Insurance Research Database. A control cohort without HIV infection, matched for age and sex, was selected for comparison. Stroke incidence until December 31, 2012 was then ascertained for all patients. A time-dependent Cox regression model was used to determine the association between OIs and incident stroke among patients with HIV.

Results: Among a total of 106,875 patients (21,375 patients with HIV and 85,500 matched controls), stroke occurred in 927 patients (0.87%) during a mean follow-up period of 5.44 years, including 672 (0.63%) ischemic strokes and 255 (0.24%) hemorrhagic strokes. After adjusting for other covariates, HIV infection was an independent risk factor for incident all-cause stroke [adjusted hazard ratio (AHR) 1.83; 95% confidence interval (CI): 1.58 to 2.13]. When the type of stroke was considered, HIV infection increased the risks of ischemic (AHR 1.33; 95% CI: 1.09 to 1.63) and hemorrhagic stroke (AHR 2.01; 95% CI: 1.51 to 2.69). The risk of incident stroke was significantly higher in patients with HIV with cryptococcal meningitis (AHR 4.40; 95% CI: 1.38 to 14.02), cytomegalovirus disease (AHR 2.79; 95% CI: 1.37 to 5.67), and Penicillium marneffei infection (AHR 2.90; 95% CI: 1.16 to 7.28).

Conclusions: Patients with HIV had an increased risk of stroke, particularly those with cryptococcal meningitis, cytomegalovirus, or P. marneffei infection.

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*Department of Internal Medicine, Section of Infectious Diseases, Taipei City Hospital, Taipei, Taiwan;

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

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

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

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

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

#Department of Health Risk Management, China Medical University, Taichung, 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; and

‡‡Department of Microbiology and 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 a grant from amfAR, The Foundation for AIDS Research, with support from the US National Institutes of Health's National Institute of Allergy and Infectious Diseases, the Eunice Kennedy Shriver National Institute of Child Health and Human Development, and the National Cancer Institute, as part of the International Epidemiologic Databases to Evaluate AIDS (IeDEA; U01AI069907). This study was also supported by a Kaohsiung Medical University “Aim for the Top Universities Grant” (No. KMU-TP103E01).

The authors have no conflicts of interest to disclose.

Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Web site (

Received July 14, 2016

Accepted October 12, 2016

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