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Immunodeficiency and Risk of Myocardial Infarction Among HIV-Positive Individuals With Access to Care

Silverberg, Michael J. PhD, MPH*; Leyden, Wendy A. MPH*; Xu, Lanfang MS; Horberg, Michael A. MD, MAS; Chao, Chun R. PhD; Towner, William J. MD§; Hurley, Leo B. MPH*; Quesenberry, Charles P. Jr PhD*; Klein, Daniel B. MD

JAIDS Journal of Acquired Immune Deficiency Syndromes: February 1st, 2014 - Volume 65 - Issue 2 - p 160–166
doi: 10.1097/QAI.0000000000000009
Clinical Science

Background: We sought to clarify the association of HIV infection and immunodeficiency on myocardial infarction (MI) risk.

Methods: We conducted a cohort study from 1996 to 2009 of HIV-positive (HIV+) and demographically matched HIV-negative (HIV) Kaiser Permanente California health plan members. Rate ratios (RRs) were obtained from Poisson regression models comparing MI incidence rates between HIV+ (overall and stratified by recent and nadir CD4 count, and recent HIV RNA levels) and HIV subjects, adjusting for age, sex, calendar era, race/ethnicity, census-based socioeconomic status, smoking, alcohol/drug abuse, overweight/obesity, diabetes, hypertension, and lipid-lowering therapy. Among HIV+ subjects, we also evaluated the independent association of CD4, HIV RNA, and antiretroviral therapy (ART) use.

Results: The study population included 22,081 HIV+ and 230,069 HIV subjects. The crude MI incidence rate per 100,000 person-years was 283 and 165 for HIV+ and HIV subjects, respectively, with an adjusted RR of 1.4 [95% confidence interval (CI): 1.3 to 1.6]. Compared with HIV subjects (reference), MI rates were similar for HIV+ subjects with recent CD4 ≥500 cells per microliter (RR = 1.18; 95% CI: 0.96 to 1.45) and those with nadir CD4 ≥500 cells per microliter (RR = 0.85; 95% CI: 0.55 to 1.33). Among HIV+ subjects, nadir CD4 was the only HIV-specific factor associated with MIs (RR per 100 cells = 0.88; 95% CI: 0.81 to 0.96), whereas recent CD4 and HIV RNA, prior ART use, and duration of protease inhibitors and nonnucleoside reverse transcriptase inhibitors were not associated with MIs.

Conclusion: HIV+ subjects with recent or nadir CD4 ≥500 cells per microliter had similar MI rates compared with HIV subjects. Lower nadir CD4, in particular, seems to be independently associated with MIs. These results strengthen recommendations for earlier ART initiation.

*Division of Research, Kaiser Permanente Northern California, Oakland, CA;

Department of Research and Evaluation, Kaiser Permanente South California, Pasadena, CA;

Mid-Atlantic Permanente Research Institute, Kaiser Permanente Mid-Atlantic States, Rockville, MD;

§Division of Infectious Diseases, Department of Internal Medicine, Kaiser Permanente Southern California, Los Angeles, CA; and

Division of Infectious Diseases, Kaiser Permanente Northern California, Hayward, CA.

Correspondence to: Dr. Michael J. Silverberg, PhD, MPH, Division of Research, Kaiser Permanente Northern California, 2000 Broadway, Oakland, CA 94612 (e-mail:

Presented in part at the 18th Conference on Retroviruses and Opportunistic Infections, February 28, 2011, Boston, MA (paper No. 810).

Supported by research Grants from the Garfield Memorial Research Fund and Pfizer Pharmaceuticals. The funders had no role in the study design, analysis, interpretation of results, or drafting of the manuscript. W.A.L. reports research Grant support from Pfizer. L.X. reports research Grant support from Pfizer. M.A.H. reports research Grant support from Pfizer and Merck. C.R.C. reports research Grant support from Pfizer. W.J.T. reports research Grant support from Pfizer, Merck, Gilead, Bristol-Myers Squibb, ViiV Healthcare, and Vertex. L.B.H. reports research Grant support from Merck. C.P.Q. reports research Grant support from Pfizer and Merck. M.J.S. reports research Grant support from Pfizer and Merck.

The authors have no conflicts of interest to disclose.

Received May 31, 2013

Accepted September 10, 2013

© 2014 by Lippincott Williams & Wilkins