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Association of Markers of Hemostasis With Death in HIV-Infected Women

Kiefer, Elizabeth MD, MPH*; Hoover, Donald R. PhD, MPH; Shi, Qiuhu PhD; Kuniholm, Mark H. PhD§; Augenbraun, Michael MD; Cohen, Mardge H. MD; Golub, Elizabeth T. PhD, MPH#; Kaplan, Robert C. PhD§; Liu, Chenglong MD, PhD**; Nowicki, Marek PhD††; Tien, Phyllis C. MD, MSc‡‡; Tracy, Russell P. PhD§§; Anastos, Kathryn MD§,‖‖

JAIDS Journal of Acquired Immune Deficiency Syndromes: 1 November 2014 - Volume 67 - Issue 3 - p 287–294
doi: 10.1097/QAI.0000000000000306
Clinical Science

Abstract: In HIV negatives, markers of hemostasis, including D-dimer, factor VIII, plasminogen activator inhibitor-1 antigen (PAI-1), and total protein S are associated with all-cause and cardiovascular disease mortality. In HIV positives, studies of D-dimer and factor VIII with death were limited to short follow-up; associations of PAI-1 and total protein S with death have not been examined. In 674 HIV-infected women from the Women's Interagency HIV Study, markers from the first visit after enrollment were exposures of interest in multivariate analyses of death (AIDS and non-AIDS) in separate models at 5 and 16 years. There were 87 AIDS and 44 non-AIDS deaths at 5 years, and 159 AIDS and 113 non-AIDS deaths at 16 years. An inverse association of total protein S quartiles with non-AIDS deaths was observed at 5 (P trend = 0.002) and 16 years (P trend = 0.02); there was no association with AIDS deaths. The third quartile of PAI-1 was associated with AIDS deaths at 5 [hazard ratio (HR) = 4.0; 95% confidence interval (CI): 1.9 to 8.4] and 16 years (HR = 3.4; 95% CI: 1.9 to 5.9); and with non-AIDS deaths at 5 years (HR = 4.8; 95% CI: 1.6 to 13.9). D-dimer and factor VIII were not associated with AIDS or non-AIDS death at 5 or 16 years. Lower total Protein S was a consistent marker of non-AIDS death. We found no association between D-dimer with AIDS or non-AIDS death, in contrast to previous studies showing increased short-term (<5 years) mortality, which may represent sex differences or population heterogeneity. Given longer survival on highly active antiretroviral therapy, further studies of these markers are needed to determine their prognostic value.

*John A. Burns School of Medicine, University of Hawaii, Honolulu, HI;

Institute for Health, Health Care Policy and Aging Research, Rutgers University, Piscataway, NJ;

New York Medical College, Valhalla, NY;

§Albert Einstein College of Medicine, Bronx, NY;

State University at Downstate Medical Center, Brooklyn, NY;

Stroger Hospital and Rush University, Chicago, IL;

#John Hopkins Bloomberg School of Public Health, Baltimore, MD;

**Georgetown University, Washington, DC;

††Los Angeles County and University of Southern California Medical Center, Los Angeles, CA;

‡‡University of California, San Francisco, San Francisco, CA;

§§University of Vermont, Burlington, VT; and

‖‖Montefiore Medical Center, Bronx, NY.

Correspondence to: Elizabeth Kiefer, MD, MPH, University Clinical, Educational and Research Associates 550 South Beretania Street, Suite 501 Honolulu, HI 96813 (e-mail: emkiefer@hawaii.edu).

The WIHS is funded by the National Institute of Allergy and Infectious Diseases (UO1-AI-35004, UO1-AI-31834, UO1-AI-34994, UO1-AI-34989, UO1-AI-34993, and UO1-AI-42590) and by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (UO1-HD-32632). The study is cofunded by the National Cancer Institute, the National Institute on Drug Abuse, and the National Institute on Deafness and Other Communication Disorders. Funding is also provided by the National Center for Research Resources (UCSF-CTSI Grant UL1 RR024131).

R.C.K. cites additional funding from National Institutes of Health/National Heart Lung and Blood Institute (1R21HL120394 and 1R01HL095140). The remaining authors have no conflicts of interest to disclose.

Data in this article were collected by the Women's Interagency HIV Study (WIHS) Collaborative Study Group with centers (Principal Investigators) at New York City/Bronx Consortium (Kathryn Anastos); Brooklyn, NY (Howard Minkoff); Washington DC Metropolitan Consortium (Mary Young); The Connie Wofsy Study Consortium of Northern California (Ruth Greenblatt); Los Angeles County/Southern California Consortium (Alexandra Levine); Chicago Consortium (Mardge Cohen); Data Coordinating Center (Stephen Gange).

Principal Investigators: UAB-MS WIHS (Michael Saag, Mirjam-Colette Kempf, and Deborah Konkle-Parker), U01-AI-103401; Atlanta WIHS (Ighovwerha Ofotokun and Gina Wingood), U01-AI-103408; Bronx WIHS (Kathryn Anastos), U01-AI-035004; Brooklyn WIHS (Howard Minkoff and Deborah Gustafson), U01-AI-031834; Chicago WIHS (Mardge Cohen), U01-AI-034993; Metropolitan Washington WIHS (Mary Young), U01-AI-034994; Miami WIHS (Margaret Fischl and Lisa Metsch), U01-AI-103397; UNC WIHS (Adaora Adimora), U01-AI-103390; Connie Wofsy Women's HIV Study, Northern California (Ruth Greenblatt, Bradley Aouizerat, and Phyllis Tien), U01-AI-034989; WIHS Data Management and Analysis Center (Stephen Gange and Elizabeth Golub), U01-AI-042590; Southern California WIHS (Alexandra Levine and Marek Nowicki), U01-HD-032632 (WIHS I – WIHS IV). The WIHS is funded primarily by the National Institute of Allergy and Infectious Diseases (NIAID), with additional co-funding from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), the National Cancer Institute (NCI), the National Institute on Drug Abuse (NIDA), and the National Institute on Mental Health (NIMH). Targeted supplemental funding for specific projects is also provided by the National Institute of Dental and Craniofacial Research (NIDCR), the National Institute on Alcohol Abuse and Alcoholism (NIAAA), the National Institute on Deafness and other Communication Disorders (NIDCD), and the NIH Office of Research on Women's Health. WIHS data collection is also supported by UL1-TR000004 (UCSF CTSA) and UL1-TR000454 (Atlanta CTSA).

The contents of this publication are solely the responsibility of the authors and do not necessarily represent the official views of the National Institutes of Health.

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Received January 13, 2014

Accepted June 26, 2014

© 2014 by Lippincott Williams & Wilkins