Immunologic predictors of coronary artery calcium progression in a contemporary HIV cohort

Baker, Jason V.a,b; Hullsiek, Katherine Hupplerc; Singh, Amritd; Wilson, Eleanord; Henry, Keitha,b; Lichtenstein, Kene; Onen, Nurf; Kojic, Ernag; Patel, Pragnah; Brooks, John T.h; Hodis, Howard N.i; Budoff, Mattj; Sereti, Irinid; for the CDC SUN Study Investigators

doi: 10.1097/QAD.0000000000000145
Clinical Science

Background: Identifying immunologic mechanisms that contribute to premature cardiovascular disease (CVD) among HIV-positive patients will inform prevention strategies.

Methods: Coronary artery calcium (CAC) progression was studied in an HIV cohort. Immunophenotypes were measured on baseline cryopreserved peripheral blood mononuclear cells using multicolor flow cytometry. Logistic regression identified predictors of CAC progression after adjusting for traditional and HIV-related risk factors.

Results: Baseline characteristics for the analysis cohort (n = 436) were median age 42 years, median CD4+ cell count 481 cells/μl, and 78% receiving antiretroviral therapy. Higher frequencies of CD16+ monocytes were associated with greater likelihood of CAC progression, after adjusting for traditional and HIV risk factors [odds ratio per doubling was 1.66 for CD14+/CD16+ (P = 0.02), 1.36 for CD14dim/CD16+ (P = 0.06), and 1.69 for CD14var/CD16+ (P = 0.01)]. Associations for CD16+ monocytes persisted when restricted to participants with viral suppression. We found no significant associations for CAC progression with other cellular phenotypes, including T-cell activation and senescence markers.

Conclusion: Circulating CD16+ monocytes, potentially reflecting a more pro-atherogenic subpopulation, independently predicted greater CAC progression among HIV-infected persons at low risk for AIDS. In contrast to T-cell abnormalities classically associated with AIDS-related disease progression, these data highlight the potential role of monocyte activation in HIV-related CVD risk.

aDepartment of Medicine, University of Minnesota

bDivision of Infectious Diseases, Hennepin County Medical Center

cDivision of Biostatistics, University of Minnesota, Minneapolis, Minnesota

dNational Institute of Allergy and Infectious Disease (NIAID), NIH, Bethesda, Maryland

eNational Jewish Medical and Research Center, Denver, Colorado

fWashington University School of Medicine, St Louis, Missouri

gMiriam Hospital, Providence, Rhode Island

hDivision of HIV/AIDS Prevention, Centers for Disease Control and Prevention, Atlanta, Georgia

iAtherosclerosis Research Unit, University of Southern California

jLos Angeles Biomedical Research Institute at Harbor-UCLA, Los Angeles, California, USA.

Correspondence to Jason Baker, MD, MS, 701 Park Avenue (MC G5), Minneapolis, MN 55415, USA. Tel: +1 612 873 2705; e-mail: baker459@umn.edu

Received 22 September, 2013

Revised 8 November, 2013

Accepted 8 November, 2013

Conference on Retroviruses and Opportunistic Infections, Atlanta, GA, 3–6 March 2013, Abstract #66LB.

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