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Cumulative Human Immunodeficiency Viremia, Antiretroviral Therapy, and Incident Myocardial Infarction

Delaney, Joseph A.a; Nance, Robin M.a; Whitney, Bridget M.a; Crane, Heidi M.a; Williams-Nguyen, Jessicaa; Feinstein, Mathew J.b; Kaplan, Robert C.c; Hanna, David B.c; Budoff, Matthew J.d; Drozd, Daniel R.a; Burkholder, Greere; Mugavero, Michael J.e; Mathews, William C.f; Moore, Richard D.g; Eron, Joseph J.h; Hunt, Peter W.i; Geng, Elvini; Saag, Michael S.e; Kitahata, Mari M.a; Heckbert, Susan R.a

doi: 10.1097/EDE.0000000000000930
Infectious Diseases

Background: People living with HIV are at risk of increased myocardial infarction (MI). Cumulative HIV viral load (VL) has been proposed as a better measure of HIV inflammation than other measures of VL, like baseline VL, but its associations with MI are not known.

Methods: The multisite Centers for AIDS Research Network of Integrated Clinical Systems (CNICS) cohort includes clinical data and centrally adjudicated MI with distinction between atheroembolic MI (type 1) and MI related to supply–demand mismatch (type 2). We examined CNICS participants who were not on antiretroviral therapy (ART) at enrollment. Cumulative VL (copy-days of virus) from 6 months after enrollment was estimated with a time-weighted sum using the trapezoidal rule. We modeled associations of cumulative and baseline VL with MI by type using marginal structural Cox models. We contrasted the 75% percentile of the VL distribution with the 25% percentile.

Results: Among 11,324 participants, 218 MIs occurred between 1996 and 2016. Higher cumulative VL was associated with risk of all MI (hazard ratio [HR] = 1.72; 95% confidence interval [CI] = 1.26, 2.36), type 1 MI (HR = 1.23; 95% CI = 0.78, 1.96), and type 2 MI (HR = 2.52; 95% CI = 1.74, 3.66). While off ART, cumulative VL had a stronger association with type 1 MI (HR = 2.13; 95% CI = 1.15, 3.94) than type 2 MI (HR = 1.25; 95% CI = 0.70, 2.25). Baseline VL was associated with all MI (HR = 1.60; 95% CI = 1.28, 2.01), type 1 MI (HR = 1.73; 95% CI = 1.26, 2.38), and type 2 MI (HR = 1.51; 95% CI = 1.10, 2.08).

Conclusions: Higher cumulative and baseline VL is associated with all MI, with a particularly strong association between cumulative VL and type 2 MI.

From the aUniversity of Washington, Seattle, WA

bNorthwestern University, Chicago, IL

cAlbert Einstein College of Medicine, Bronx, NY

dLos Angeles Biomedical Research Institute, Torrance, CA

eUniversity of Alabama, Birmingham, AL

fUniversity of California San Diego, San Diego, CA

gJohns Hopkins University, Baltimore, MD

hUniversity of North Carolina, Chapel Hill, NC

iUniversity of California San Francisco, San Francisco, CA.

Submitted January 26, 2018; accepted September 24, 2018.

This work was supported by several grants from the National Institutes of Health (Centers for AIDS Research Network of Integrated Clinical Systems [CNICS] R24 AI067039, CNICS myocardial infarction [MI] supplement R24S AI067039, National Heart, Lung, and Blood Institute (NHLBI) R01 HL126538 and R56 AG057262, University of Washington Center for AIDS Research National Institute of Allergy and Infectious Diseases (NIAID) grant P30 AI027757, Third Coast Center for AIDS Research NIAID grant P30AI117943, K01-HL-137557, P30 AI094189, and U01 DA036935). The work was also supported by a grant from the American Heart Association (16FTF31200010).

The authors report no conflicts of interest.

Data and code: Statistical code is available upon request to rmnance@uw.edu. Data may be shared with any investigator as a part of the Centers for AIDS Research Network of Integrated Clinical Systems (CNICS) data collaboration with an approved concept proposal. Instructions for data access and concept proposal forms may be found at https://www.uab.edu/cnics/submit-proposal.

Supplemental digital content is available through direct URL citations in the HTML and PDF versions of this article (www.epidem.com).

Correspondence: Joseph A. Delaney, Collaborative Health Studies Coordinating Center, University of Washington, 6200 NE 74th Street, Building 29, Suite 210, Box 354922, Seattle, WA 98115. E-mail: jacd@uw.edu.

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