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

Joseph A. Delaney; Robin M. Nance; Bridget M. Whitney; Heidi M. Crane; Jessica Williams-Nguyen; Mathew J. Feinstein; Robert C. Kaplan; David B. Hanna; Matthew J. Budoff; Daniel R. Drozd; Greer Burkholder; Michael J. Mugavero; William C. Mathews; Richard D. Moore; Joseph J. Eron; Peter W. Hunt; Elvin Geng; Michael S. Saag; Mari M. Kitahata; Susan R. Heckbert

doi:10.1097/EDE.0000000000000930

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

Joseph A. Delaney, Robin M. Nance, Bridget M. Whitney, Heidi M. Crane, Jessica Williams-Nguyen, Mathew J. Feinstein, Robert C. Kaplan, David B. Hanna, Matthew J. Budoff, Daniel R. Drozd, Greer Burkholder, Michael J. Mugavero, William C. Mathews, Richard D. Moore, Joseph J. Eron, Peter W. Hunt, Elvin Geng, Michael S. Saag, Mari M. Kitahata, Susan R. Heckbert

Epidemiology & Population Health

Research output: Contribution to journal › Article › peer-review

4 Scopus citations

Abstract

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.

Original language	English (US)
Pages (from-to)	69-74
Number of pages	6
Journal	Epidemiology
Volume	30
Issue number	1
DOIs	https://doi.org/10.1097/EDE.0000000000000930
State	Published - Jan 1 2019

Keywords

HIV
Marginal structural models
cohort studies
inverse probability weighting
myocardial infarction

ASJC Scopus subject areas

Epidemiology

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10.1097/EDE.0000000000000930

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Delaney, J. A., Nance, R. M., Whitney, B. M., Crane, H. M., Williams-Nguyen, J., Feinstein, M. J., Kaplan, R. C., Hanna, D. B., Budoff, M. J., Drozd, D. R., Burkholder, G., Mugavero, M. J., Mathews, W. C., Moore, R. D., Eron, J. J., Hunt, P. W., Geng, E., Saag, M. S., Kitahata, M. M., & Heckbert, S. R. (2019). Cumulative Human Immunodeficiency Viremia, Antiretroviral Therapy, and Incident Myocardial Infarction. Epidemiology, 30(1), 69-74. https://doi.org/10.1097/EDE.0000000000000930

Cumulative Human Immunodeficiency Viremia, Antiretroviral Therapy, and Incident Myocardial Infarction. / Delaney, Joseph A.; Nance, Robin M.; Whitney, Bridget M.; Crane, Heidi M.; Williams-Nguyen, Jessica; Feinstein, Mathew J.; Kaplan, Robert C.; Hanna, David B.; Budoff, Matthew J.; Drozd, Daniel R.; Burkholder, Greer; Mugavero, Michael J.; Mathews, William C.; Moore, Richard D.; Eron, Joseph J.; Hunt, Peter W.; Geng, Elvin; Saag, Michael S.; Kitahata, Mari M.; Heckbert, Susan R.

In: Epidemiology, Vol. 30, No. 1, 01.01.2019, p. 69-74.

Research output: Contribution to journal › Article › peer-review

Delaney, JA, Nance, RM, Whitney, BM, Crane, HM, Williams-Nguyen, J, Feinstein, MJ, Kaplan, RC , Hanna, DB, Budoff, MJ, Drozd, DR, Burkholder, G, Mugavero, MJ, Mathews, WC, Moore, RD, Eron, JJ, Hunt, PW, Geng, E, Saag, MS, Kitahata, MM & Heckbert, SR 2019, 'Cumulative Human Immunodeficiency Viremia, Antiretroviral Therapy, and Incident Myocardial Infarction', Epidemiology, vol. 30, no. 1, pp. 69-74. https://doi.org/10.1097/EDE.0000000000000930

Delaney, Joseph A. ; Nance, Robin M. ; Whitney, Bridget M. ; Crane, Heidi M. ; Williams-Nguyen, Jessica ; Feinstein, Mathew J. ; Kaplan, Robert C. ; Hanna, David B. ; Budoff, Matthew J. ; Drozd, Daniel R. ; Burkholder, Greer ; Mugavero, Michael J. ; Mathews, William C. ; Moore, Richard D. ; Eron, Joseph J. ; Hunt, Peter W. ; Geng, Elvin ; Saag, Michael S. ; Kitahata, Mari M. ; Heckbert, Susan R. / Cumulative Human Immunodeficiency Viremia, Antiretroviral Therapy, and Incident Myocardial Infarction. In: Epidemiology. 2019 ; Vol. 30, No. 1. pp. 69-74.

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title = "Cumulative Human Immunodeficiency Viremia, Antiretroviral Therapy, and Incident Myocardial Infarction",

abstract = "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.",

keywords = "HIV, Marginal structural models, cohort studies, inverse probability weighting, myocardial infarction",

author = "Delaney, {Joseph A.} and Nance, {Robin M.} and Whitney, {Bridget M.} and Crane, {Heidi M.} and Jessica Williams-Nguyen and Feinstein, {Mathew J.} and Kaplan, {Robert C.} and Hanna, {David B.} and Budoff, {Matthew J.} and Drozd, {Daniel R.} and Greer Burkholder and Mugavero, {Michael J.} and Mathews, {William C.} and Moore, {Richard D.} and Eron, {Joseph J.} and Hunt, {Peter W.} and Elvin Geng and Saag, {Michael S.} and Kitahata, {Mari M.} and Heckbert, {Susan R.}",

note = "Funding Information: 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).",

year = "2019",

month = jan,

day = "1",

doi = "10.1097/EDE.0000000000000930",

language = "English (US)",

volume = "30",

pages = "69--74",

journal = "Epidemiology",

issn = "1044-3983",

publisher = "Lippincott Williams and Wilkins",

number = "1",

}

TY - JOUR

T1 - Cumulative Human Immunodeficiency Viremia, Antiretroviral Therapy, and Incident Myocardial Infarction

AU - Delaney, Joseph A.

AU - Nance, Robin M.

AU - Whitney, Bridget M.

AU - Crane, Heidi M.

AU - Williams-Nguyen, Jessica

AU - Feinstein, Mathew J.

AU - Kaplan, Robert C.

AU - Hanna, David B.

AU - Budoff, Matthew J.

AU - Drozd, Daniel R.

AU - Burkholder, Greer

AU - Mugavero, Michael J.

AU - Mathews, William C.

AU - Moore, Richard D.

AU - Eron, Joseph J.

AU - Hunt, Peter W.

AU - Geng, Elvin

AU - Saag, Michael S.

AU - Kitahata, Mari M.

AU - Heckbert, Susan R.

N1 - Funding Information: 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).

PY - 2019/1/1

Y1 - 2019/1/1

N2 - 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.

AB - 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.

KW - HIV

KW - Marginal structural models

KW - cohort studies

KW - inverse probability weighting

KW - myocardial infarction

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